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Research into MAP as the cause of Crohn's

It's rather semi official, but still..

Comment from one of the prof. John Hermon-Taylor's team member on the statement "MAP found in ~95% of Crohn's sufferers":

"The 95% is old data. Currently we are finding MAP (in varying degrees) in 100% of those tested, but need to complete the research before making that claim." (Original here)

Everything I can say on this is simply "WOW!". One hundred percent. No more, no less.
 
I see that there's a lot of excitement here about the vaccine in progress, but if I'm not mistaken there are other options that are currently available, reportedly effective in some patients, and cheap. I'm on a trial of Dapsone right now, a few days in. I'll let everyone know how it goes.
 
medicaljohndoe, your updates would be appreciated.

About "cheap/expensive" issue - I think in fact it's not an issue for anyone of us, undoubtedly any sum will be sacrificed for the proven cure. This excitement is rather about overall progress with research of causativity of MAP, simply vaccine team with their cheap and simple MAP test came closest to the final solution.
 
Everything I can say on this is simply "WOW!". One hundred percent. No more, no less.
Yes, but caution is needed. I have been tested twice by Prof John Hermon-Taylor, both times positive for MAP. Although the test design is very good and John is very confident of the results, it still needs to be properly validated to confirm that what it is detecting is MAP and not another similar but harmless bacteria.

This is why fund raising for the MAP Test is still on-going as is the research work. So, I would advise people to wait for the patent to be granted and the paper to be published in a refereed journal before cracking open the champagne, which hopefully should be some time this year. :)
 

my little penguin

Moderator
Staff member
Agree with JMC
95-100% of what sample size and what exclusion criteria etc
Any data needs validation especially new testing .
Good luck
 
Oxidative stress due to Mycobacterium avium subspecies paratuberculosis (MAP) infection upregulates selenium-dependent GPx activity

http://gutpathogens.biomedcentral.com/articles/10.1186/s13099-016-0090-8

Conclusion
This study demonstrated a strong correlation between MAP and the elevation of GPx activity. This was especially evident in Crohn’s patients, which further supports the association of MAP and Crohn’s disease. GPx activity may also be used to predict MAP infection status and to show that Crohn’s disease patients who are infected with MAP have higher tendency to develop oxidative stress than Crohn’s disease patients who are negative for the bacteria.
 
I've been on Dapsone now for three weeks. I started at 100mg/day but had to stop after a week due to side effects, namely clear signs of hemolytic anemia. After a few days to let my bone marrow regenerate red blood cells, I started again at 50mg/day. At the lower dose, I've had almost no notable side effects. (I weigh about 150lbs for reference--I know I'm going to have GI problems when my weight goes above 152lbs.) When I started at the lower dose, I also added a multivitamin supplement (Centrum), a 400mcg folic acid supplement, and 4000IU Vitamin D-3.

My GI symptoms have not been perfect--there have been two or three days when I have felt bloated, and I had one episode that reminded me of what things were like before my diagnosis. However, on average I'd say that I generally feel far better. On most of the days I've felt completely normal, with no GI symptoms at all. The one episode that took place also seemed less severe than previous ones. I have also noticed that I have gotten more work done in the past few days than I probably got done in the past three months, simply because I have more energy and can focus more.

My skin symptoms are not gone, but they have also improved. The most important point is that the constant itching that used to plague me is basically gone (a known effect of Dapsone), and the flaking is not nearly as bad as before. The inflammation has largely, but not completely, subsided in the few psoriatic lesions that I have. My skin is still pink, but not angry red like it was before.

In the last few months many of my facial hairs and hair along my temples have turned gray--not totally impossible since I'm 32--and most have remained that way, but one has started growing back in black. I saw this in a few other hairs previously after starting to take the multivitamin more regularly. I suspect it's related to the folic acid supplement, though I now also wonder if perhaps I should be taking additional amounts of B-12.

Overall I would suggest inquiring about Dapsone (and folic acid or other Vitamin B supplementation) as possible treatment options, especially for those with skin manifestations of IBD.
 
Yes, but caution is needed. I have been tested twice by Prof John Hermon-Taylor, both times positive for MAP. Although the test design is very good and John is very confident of the results, it still needs to be properly validated to confirm that what it is detecting is MAP and not another similar but harmless bacteria.

This is why fund raising for the MAP Test is still on-going as is the research work. So, I would advise people to wait for the patent to be granted and the paper to be published in a refereed journal before cracking open the champagne, which hopefully should be some time this year. :)
I really hope you are right about it being this year. Thank you for the updates
 
Not directly CD related and 14 years old paper, but still extremely interesting:

"This report suggests a pathogenic role of MAP for immunocompromised patients, raising the question of whether this strain so far has not been detected because of its limited growth, whether it has been misidentified as M. avium, or whether its occurrence in infections is low. However, herd prevalence of bovine paratuberculosis has been reported to range from 7% to 55% in Europe and to reach approximately 40% in stocks of >300 animals in the United States (4). Thus, consumption of inadequately pasteurized dairy products may be a possible risk for infection, especially for immunocompromised patients."

http://wwwnc.cdc.gov/eid/article/8/7/01-0388_article
 
Does anyone know what the time frame is for drugs to be approved for prescription following phase 3 clinical trials? I am interested to know for the ongoing MAP antibiotic trial going on around the world. If the results are good when can we get prescribed this drug?
 
Does anyone know what the time frame is for drugs to be approved for prescription following phase 3 clinical trials? I am interested to know for the ongoing MAP antibiotic trial going on around the world. If the results are good when can we get prescribed this drug?
My guess, 2018/2019.

Here I'm speaking about the FDA process, and not the European.

Typically the Phase III stage takes 3 years to complete, and if the drug is safe and effective, then another 2 years for it to go through new drug application stage for final approval. This process may be sped up if the company had received fast-track designation at the time of their application.

As far as I can tell, the RedHill RHB-104 trials still have a ways to go. They recently finished enrolling half of the patients and once those complete 26 weeks of therapy, the company will release preliminary results, expected in second half of this year. They're probably continuing to recruit the second half of their patients and then those will need to complete their 26 week course. At the current rate that'll probably wrap up mid-2017. Then the NDA and hopefully approval.

RedHill is probably pretty motivated to get the drug to market; by all indications, they'll only have patent cover until 2029.
 
and if the drug is safe and effective, then another 2 years for it to go through new drug application stage for final approval.
Stop and think for one minute, what are they actually doing for 2 whole years to get final approval? The sluggishness of these processes drives me crazy! I bet you could do it in a couple of days with proper focus!
 
Stop and think for one minute, what are they actually doing for 2 whole years to get final approval? The sluggishness of these processes drives me crazy! I bet you could do it in a couple of days with proper focus!
This FDA article gives a pretty good run-down. In the application, they're looking at pre-clinical (animal studies), phase I-III data, safety and effectiveness results, inspecting manufacturing facilities, etc. I have read other places they may be reviewing as much as 100,000 pages of supporting documents. It's a laborious process.

I'm not rationalizing the long approval times, but can understand why, as they are generally responsible for public health, including veterinary medicine, our food supply, tobacco, cosmetics, etc. Out of their $4.7B budget, about $1.3B is allocated toward human drugs, with another $300M to biologics.

And, it's a bureaucracy.
 
So, Xeridea, Prof JHT's vaccine which is due to start phase 1 trials this year, and phase 2 next year, will probably not be available, if all goes well, until 2020 at the earliest by this reckoning?
 
So, Xeridea, Prof JHT's vaccine which is due to start phase 1 trials this year, and phase 2 next year, will probably not be available, if all goes well, until 2020 at the earliest by this reckoning?
I don't know Mattie, and will defer to someone more closely tied to the CMV effort to respond.
 
I don't know Mattie, and will defer to someone more closely tied to the CMV effort to respond.
According to the "crohn's MAP vaccine" website access to the vaccine should be granted to the most severely ill patients in the end of 2017:

"As soon as there is evidence of safety and efficacy, we can apply for use of the vaccine on compassionate grounds; this will enable people who wish to have the vaccine but are unable to be part of the trial to access it on a named-patient basis outside of the trial.

Indeed, under the newly proposed ‘Early Access to Medicines’ scheme in the UK, severely ill patients who have failed existing treatments may be granted access to new medicines that are proven to be safe, even before efficacy has been fully established.

This means that the earliest the vaccine could be made available to patients on a named-patient basis would be late 2017.
"​

So, in advance: happy new year 2018! =)
 
Thanks. From what I understand about 'named patient basis' programmes, the patient has to be seriously ill and have exhausted all other available forms of treatment. An application to be considered under the named patient programme will most probably have to be made by the doctor and not the patient? Am I correct here? If so, can anyone hazard a guess as to the earliest date
the vaccine, provided it proves to be the answer we are all looking for, could be made available to those who don't fall into the above category?
 
can anyone hazard a guess as to the earliest date
the vaccine, provided it proves to be the answer we are all looking for, could be made available to those who don't fall into the above category?
From the same source:

In addition, following the demonstration of safety and efficacy, it is anticipated that the Vaccine technology would be licenced to a pharmaceutical company to make it available to all who need it through health services worldwide -as part of this, larger Phase 3 trials inviting wider participation would be expected.

I understand it as such: vaccine (or placebo of course, 50/50..) will be available to anyone who is willing to participate and is eligible for phase 3 trial. If phase 2 finishes by the end of 2017, we could be optimistic enough to expect phase 3 to start in the beginning of 2018.

That's why i said "happy new year 2018!" =)

Not sure, but common sense says that for ethical reasons those who got in placebo group still should be vaccinated, but later, after demonstration of the undoubtful fail of placebo for this certain patient.
 
New post at The Crohn's Infection by Dr. Robert Click, of Dietzia fame. Dietzia seems to be a probiotic combating the effects of MAP in cattle, and may have human applicability. An intro summarizing the published research and giving some background can be found here:

http://thecrohnsinfection.org/whats-new/

Would be so amazing if this worked! Very excited to see if there will be trials starting in the future.
 
It's interesting that this approach is effective against "16 MAP clinical strains and 19 other mycobacteria"

RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis


http://gutpathogens.biomedcentral.com/articles/10.1186/s13099-016-0115-3

Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated as an etiological agent of Crohn’s disease (CD), a debilitating chronic inflammatory bowel disease. Clarithromycin (CLA), clofazimine (CLO), rifabutin (RIF) and other antibiotics have been used individually or in combinations with other drugs to treat mycobacterial diseases including CD. The treatment has varied by regimen, dosage, and duration, resulting in conflicting outcomes and additional suffering to the patients. RHB-104, a drug formula with active ingredients composed of (63.3 %) CLA, (6.7 %) CLO, and (30 %) RIF, has been recently subjected to investigation in an FDA approved Phase III clinical trial to treat patients with moderate to severe CD. In this study, we determined the efficacy of RHB-104 active ingredients against MAP strains isolated from the blood, tissue, and milk of CD patients. Based on fluorescence quenching technology using the Bactec MGIT Para-TB medium, we determined the minimum inhibitory concentration (MIC) of CLA, CLO, RIF individually and in dual and triple combinations against 16 MAP clinical strains and 19 other mycobacteria.
 
It's interesting that this approach is effective against "16 MAP clinical strains and 19 other mycobacteria"

RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis


http://gutpathogens.biomedcentral.com/articles/10.1186/s13099-016-0115-3

Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated as an etiological agent of Crohn’s disease (CD), a debilitating chronic inflammatory bowel disease. Clarithromycin (CLA), clofazimine (CLO), rifabutin (RIF) and other antibiotics have been used individually or in combinations with other drugs to treat mycobacterial diseases including CD. The treatment has varied by regimen, dosage, and duration, resulting in conflicting outcomes and additional suffering to the patients. RHB-104, a drug formula with active ingredients composed of (63.3 %) CLA, (6.7 %) CLO, and (30 %) RIF, has been recently subjected to investigation in an FDA approved Phase III clinical trial to treat patients with moderate to severe CD. In this study, we determined the efficacy of RHB-104 active ingredients against MAP strains isolated from the blood, tissue, and milk of CD patients. Based on fluorescence quenching technology using the Bactec MGIT Para-TB medium, we determined the minimum inhibitory concentration (MIC) of CLA, CLO, RIF individually and in dual and triple combinations against 16 MAP clinical strains and 19 other mycobacteria.
Hi JMC - that is very interesting. The link won't work for me though, I think it may be my computer....any update on the vaccine status timeline? I keep checking and it is not updated. I am so anxious to know that at least some of the trials have begun!

I am also following the Qu SSI - I think the combination of the two can be a powerful way to clear out this infection in the body....
 
I also found this article very interesting in that they tried each antibiotic alone and each of the combinations of just two together, and found that the Mean Inhibitory Concentration was the lowest when the three were used together. They have a synergistic effect together. I guess the refrain of "we're all stronger together" applies not only to us, but to our antibiotics as well!
 
Finally got it to open! This is very interesting - the Redhill trial is still going on until November, correct? Based on the info I see at ClinicalTrials.gov. But if this is any indication - this would be great. The only thing I am concerned about is that the results of the Redhill can be skewed - I mean, I am hoping they enroll those that are positive for MAP, kinda of like SSI Qu biologics - they have to have positive AIEC cultures to be enrolled based on the website criteria (or maybe I am mistaken)? Whatever the case, I am so anxious to see the results of this!
 
I keep checking and it is not updated. I am so anxious to know that at least some of the trials have begun!
I don't know when this will be completed, I have asked, but not received a reply. Please contact Amy or John Hermon-Taylor directly so they know you are interested.
 
Thanks for all this information.

It has made me cast my mind back to Ireland 1976 living on my father-in-laws farm for a year and drinking unpasteurized milk.

The old man got TB from the cattle and I suffered the worst bout of food poisoning ever while I was living there and I was never quite right after that.
We returned to the UK and in 1984 I was diagnosed with IBS then finally Crohn's.

Have to wonder if that milk had MAP in it but I did have three maternal aunts with Crohn's, all who drank unpasteurized farm milk in the 1930s onward.

:shifty-t:
 
Yikes Kaevata! Sorry you have CD. Sounds like your family has history of Crohn's so there may be some genetic susceptibility there. My entire family is littered with autoimmune diseases as well, so I think I probably have the mutations they look for in CD. Plus to compound things in your case, unpasteurized milk was probably doing you no favors. From what you say, sound like something in that milk triggered your disease. I was triggered by a bad stomach flu, and I've heard of others who can pinpoint the time when their disease began to a solid event. It would make sense with the MAP theory of CD at least.

I've also heard speculation that IBS may really just be pre-Crohn's, so it's interesting that you had IBS which escalated into CD. Hope your disease is under control now!
 
But I just noticed that the human trial piece got pushed out until 2018!:-(
I think the more interesting date(s) are when the trial(s) will actually start. I would be very happy to see the phase I trial start this year. Once it begins, the end date will become clearer. Phase IIa is also currently unfunded, but I would not say that is a big concern right now.
 
I think the more interesting date(s) are when the trial(s) will actually start. I would be very happy to see the phase I trial start this year. Once it begins, the end date will become clearer. Phase IIa is also currently unfunded, but I would not say that is a big concern right now.
Yes, I agree. I just want at least some data presented -maybe then everyone will get on the bandwagon funding wise. For Qu Biologics, it took them a while to get the word out but one you have some data to show that it works, I think that will be a huge step forward!
 
This isn't from RedHill, though it's interesting. I think this is a guy who evaluates pharma companies, so he's just speculating on the cost and what the market could bear.
 
This isn't from RedHill, though it's interesting. I think this is a guy who evaluates pharma companies, so he's just speculating on the cost and what the market could bear.
Yes, I saw that it is from an analyst discussing the valuation of Redhill. :) But made me wonder - cost-wise what it would be, and if it turns out well - which I really am certain it will - if insurance will cover it. Same with the MAP vaccine...either way, I am soo looking forward to the results!
 
Scared - guessing it will be priced based on other non-generic Crohn's meds, but it will be interesting to see if the price may be lower since the active ingredients in this pill are available in generics. Certainly, this pill has big advantages in combining them (from a previous study about how they're synergistic) and clofaz isn't really available in the US, but people are basically using these three drugs now, just seperately. I wonder if that will lower the cost some? The RedHill pill may also have some secret non-active ingredient that does something critical, either for absoprtion, buffering, etc which is why it may work better than the generics. Plus, the dosage is highly adaptable in the RedHill pill (since the daily dose is 10 pills) so it could be tapered to the individual based on body weight. A huge advantage if it gets approved for pediatric cases.Much harder to do that with the generics since some only come in standard dosages.

Also, if the FDA approves it for CD, I'm guessing that most likely insurance will cover it. I think it's the off label stuff that's harder to get covered, but once it's approved, the insurance usually covers all of the other standard CD treatments. Why not this one too?

Not sure about the Vaccine. If it goes through the US FDA application process as an approved CD treatment, then probably that would be covered too. I think the government approval is key for insurance coverage.
 
Very interesting Scared. Plus, it's another venture that Nestle is involved in. Takeda and Johnson & Johnson are partners as well. The microbiome research is drawing some big names. It will be interesting to see how this AIEC theory works in CD.
 
Just saw this publication but can't seem to find the actual paper!

Increased Milk Consumption but Decreased Risk of Crohn's Disease (CD): Critical Evidence Negated Causative Role of Mycobacterium avium Subspecies paratuberculosis (MAP) in CD
 
Just saw this publication but can't seem to find the actual paper!

Increased Milk Consumption but Decreased Risk of Crohn's Disease (CD): Critical Evidence Negated Causative Role of Mycobacterium avium Subspecies paratuberculosis (MAP) in CD
Does "Critical Evidence Negated Causative Role" sound like scientifically neutral humble statement? I wouldn't say so.

Why wouldn't Qin Xiaofa (the only author of this unpublished paper without abstract) add something like "magnificent, brilliant, glorious, stunning critical evidence completely, totally, entirely, wholly negated causative role" to the title?..
 
Does "Critical Evidence Negated Causative Role" sound like scientifically neutral humble statement? I wouldn't say so.

Why wouldn't Qin Xiaofa (the only author of the publication) add something like "magnificent, brilliant, glorious, stunning critical evidence completely, totally, entirely, totally, wholly negated causative role" to the title?..
Sounded really weird to me to be honest...that is why I was curious and wanted to read it since it just came out like a few days ago and I haven't read anything recent on MAP. Yet, it is no where to be found...except if you pay which I wont do.

And you are right, the certainty in the title based on correlation between Milk consumption (only) is odd.
 
Does "Critical Evidence Negated Causative Role" sound like scientifically neutral humble statement? I wouldn't say so.

Why wouldn't Qin Xiaofa (the only author of this unpublished paper without abstract) add something like "magnificent, brilliant, glorious, stunning critical evidence completely, totally, entirely, wholly negated causative role" to the title?..
Maybe Qin Xiaofa would like to explain this paper in more detail
 
Location
San Diego
Does "Critical Evidence Negated Causative Role" sound like scientifically neutral humble statement? I wouldn't say so.

Why wouldn't Qin Xiaofa (the only author of this unpublished paper without abstract) add something like "magnificent, brilliant, glorious, stunning critical evidence completely, totally, entirely, wholly negated causative role" to the title?..
I presume he wouldn't say that because he's trying to sound scientific. Scientific findings are usually reported in understated, cautious language. Use of over-the-top superlatives and exaggerations is the language of quacks and charlatans.
 
Location
San Diego
The fact that the Qin piece has only one author and no abstract makes me wonder whether it is an opinion piece or editorial, or maybe a review, rather than report of new data.
 
The fact that the Qin piece has only one author and no abstract makes me wonder whether it is an opinion piece or editorial, or maybe a review, rather than report of new data.
That's what I was wondering, but there is no way to know. And if it is an opinion piece, it would still be a strange way to state the title almost with certainty without data to validate. I would be interested in reading it though.
 
I've heard this basic argument before, which is "If MAP is in milk, why do those who drink more milk have less CD?" I think there's an old study about that, but the basic answer is that MAP won't do a thing to you unless you have the genetic predisposition to not allow your immune system to recognize intracellular infections and also a triggering event, like stress, a loss of someone close, Vit D deficiency, the flu, antibiotic use, some other environmental exposure that no one knows about yet. So a great study would be to only look at patients with IBS or those with the genetic predisposition for CD, randomize a huge group of them, then make half consume dairy and the other half stay away from it completly - for like 10 years. And then see which group develops higher incidence of CD. So you can see it's completely impractical. Milk isn't the only issue going on with CD. There are a whole chain of issues, and the increased MAP in milk due to more herds being infected (and especially infant formula) may result in a higher level of MAP exposure at a younger age, therefore precipitating higher CD rates in those genetically susceptible. Dr. Collins talked about this at the symposium. And it's just a theory right now.

I was trying to get this paper any way possible, but it's published in e-print ahead of the Sept. 22nd journal publication. Also, it looks like this journal is the publication of the CCFA, so it may be a bit biased, since they seem to dislike the MAP theory of CD. If I can get it, I'll let you know! Reserving judgment until I read it.
 
Location
San Diego
The quote below is taken from Dr. Qin's LinkedIn page and spells out his theory of the cause of IBD. Presumably he views MAP as a competing theory.


" Engaged in medical research in the academic for more than twenty years. More than a decade ago, a series of accidental findings made him suspect that impaired inactivation of digestive proteases due to the reduction in gut bacteria along with improved hygiene and inhibition by some dietary chemicals may have played important causative role in inflammatory bowel disease (IBD, including ulcerative colitis and Crohn's disease), which emerged and dramatically increased in last century. During the last decade he published a series of papers and proposed that damage of gut by the poorly inactivated digestive proteases may be the root cause of IBD. Not only IBD, more and more studies revealed many other diseases that are dramatically increasing in modern society, such as irritable bowel syndrome (IBS), multiple sclerosis, type I and type II diabetes, asthma, atopic eczema/ dermatitis, obesity, autism, etc, all accompanied by increased gut permeability, suggesting damage of gut barrier would have also contributed to the development of these diseases. He recently started a company, GI Biopharma Inc, with the goal to develop new treatments for these diseases."
 
New article:

J Crohns Colitis. 2016 Aug 23. pii: jjw148. [Epub ahead of print]
Inflammatory bowel disease incidence is on the continuous rise among all pediatric patients except for the very young - a nationwide registry-based study on 28-year follow-up.
Virta LJ1, Saarinen MM2, Kolho KL3.
Author information
Abstract
BACKGROUND AND AIMS:
The burden of inflammatory bowel disease (IBD) in health care is high. We conducted research on the temporal changes in the incidence of pediatric IBD (PIBD) using nationwide registry-based data in Finland.
METHODS:
All PIBD cases diagnosed at less than 20 years of age during 1987-2014 (in total, 5,415 patients) were retrieved from a database documenting reimbursements for drug costs. Incidence rates were calculated by dividing the number of annual new PIBD cases by the size of the pediatric population at risk during each calendar year. Temporal trends in the incidences of PIBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD), were estimated using Poisson regression analyses.
RESULTS:
The mean annual incidence of PIBD increased from 7/100,000 for the years 1987-1990 to 23/100,000 for the years 2011-2014. The average rate of increase was 4.1% (95% CI: 3.6-4.5) per annum. In the period 2000-2014, the increase rate in the annual incidence of UC (3.8%; 95% CI: 2.7-5.0), was steeper than for CD (2.5%; 95% CI: 1.0-3.8). The most pronounced increase occurred in UC among adolescents aged 16-19 years: 4.8% (95% CI: 2.9-6.7). For children less than 10 years of age, the rate of change remained low. Approximately 0.17% of the birth cohort for the years 1999-2000 was diagnosed with PIBD by the age of 14 years.
CONCLUSION:
The incidence of PIBD is primarily increasing among adolescents, challenging the identification of the possible environmental triggers for the disease.
 
Very interesting article:
Dig Liver Dis. 2016 Aug 5. pii: S1590-8658(16)30546-1. doi: 10.1016/j.dld.2016.07.036. [Epub ahead of print]
Occupational risk for Crohn's disease: A two-center study.
Liu S1, Ding J1, Wang M1, Wang G2, Wu X2, Feng M1, Song P1, Ren J3, Guan W4.
Author information
Abstract
BACKGROUND:
Occupational factors have been suggested as possible elements in the etiology of Crohn's disease, although evidences have not been fully obtained.
AIMS:
This study is to investigate possible associations between occupation and development of Crohn's disease.
METHODS:
This prospective study was carried out in two major hospitals during January 2010 and December 2014. Demographic and clinical data were collected for the calculation of standard incidence ratios and 95% confidence intervals by occupation.
RESULTS:
A total of 401 patients with Crohn's disease were recruited into this study. Participants were distributed into 8 major occupational groups, among which "professionists" (17.7%), "service and sales" (18.7%) and "unclassified individuals" (mainly students) (20.2%) took up the most proportions. Increased standard incidence ratios were found in "service and sales" (2.526±0.135, 95% CI: 1.939-3.290), "professionists" (4.216±0.142, 95% CI: 3.194-5.565), and most significantly, in "administrative staffs" (5.476±0.170, 95% CI: 3.926-7.639). In contrast, decreased standard incidence ratios for Crohn's disease were observed in the category of "workers in agriculture, forestry, animal husbandry, fishery and water conservancy" (0.088±0.146, 95% CIs: 0.066-0.117).
CONCLUSION:
Occupational elements are implicated in the likelihood of development of Crohn's disease.
 
Scared - I wonder if more active professions have less incidence than more sedentary desk jobs because exercise has been shown to help CD? Also thinking that the stress factor of office life may play a role too. The poor admins! Will have to read the whole thing.
 
Scared - I wonder if more active professions have less incidence than more sedentary desk jobs because exercise has been shown to help CD? Also thinking that the stress factor of office life may play a role too. The poor admins! Will have to read the whole thing.
That could be a contributing factor - who knows, maybe these active professions may have the incidence but it is under control and they are not diagnosed? but its interesting they all have to do with exposure of some kind to "nature" and consequently, could be related to healthier microbiome? I am not sure...it is really interesting all this research though, but I have yet to see one that talks about how there are different types of crohn's in the sense - MAP associated, AEIC associated...etc...
 
Something noticeably wrong just happened to US portion of Red Hill's RHB-104 study..

You can track progress of the study (as well as history of changes) here:
https://clinicaltrials.gov/ct2/show/NCT01951326

And on July 17th main parameters of the study were silently updated. Wikipedia-style history of changes for that day:
https://clinicaltrials.gov/archive/NCT01951326/2016_07_17/changes

So, two things changed:

1. Estimated Primary Completion Date was changed from 2016-07 to 2017-09
2. Estimated Study Completion Date was changed from 2016-11 to 2018-09

Also, as you can see, if earlier they were good with just 4 months between primary and final study completion dates, now they need whole year.

Honestly, I just don't know what to say..

P.S.:
On July 25th "2018-09" for Study Completion Date was changed to "2018-04" (https://clinicaltrials.gov/archive/NCT01951326/2016_07_25/changes), so current situation is:

Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: September 2017
 
Last edited:
Something noticeably wrong just happened to US portion of Red Hill's RHB-104 study..

You can track progress of the study (as well as history of changes) here:
https://clinicaltrials.gov/ct2/show/NCT01951326

And on July 17th main parameters of the study were silently updated. Wikipedia-style history of changes for that day:
https://clinicaltrials.gov/archive/NCT01951326/2016_07_17/changes

So, two things changed:

1. Estimated Primary Completion Date was changed from 2016-07 to 2017-09
2. Estimated Study Completion Date was changed from 2016-11 to 2018-09

Also, as you can see, if earlier they were good with just 4 months between primary and final study completion dates, now they need whole year.

Honestly, I just don't know what to say..

P.S.:
On July 25th "2018-09" for Study Completion Date was changed to "2018-04" (https://clinicaltrials.gov/archive/NCT01951326/2016_07_25/changes), so current situation is:

Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: September 2017
I remember seeing that too...just like the map vaccine delay...but its either they saw negative results and want to dig in more to see why it didnt have the effect (they said they wanted to learn more about the patient population), or they had great results (but why would they not want to publish as soon as possible), so I am worried that this might be not a pro map sotuation:( I don't think that would really hurt the map crohns link. But, if there wasn't a link, how could they discount the obvious benefit it gave come people? I mean, its not a massive placebo that has worked on so many...I just wish some validation would come about already. I really believe that if it were the cauae (and I do believe it is for many), that a study like this could get more buy in and more people involved in finding a permanent solution to this mystery.
 
It may be they aren't able to recruit enough patients. I think in June they had met only 75% of their recruitment goal for this study (200 out of 270). The study has 26 weeks of treatment, plus evaluation of duration/maintenance of remission at 52 weeks. I don't know how all this plays into the delays, but it's one explanation.
 
Here's from their Aug. 11th Semi annual research report. Looks like they want to get full enrollment, and they are considering some type of US protocol change. But the key thing is that RedHill apparently still remains blinded, so they can't be increasing the timelines because it either works/doesn't work, which I see as good news. I'd rather them take their time and get it right than rush and have another unreliable study, but yes, it's SOOO hard to wait! Especially when GIs will be more likely to prescribe AMAT once results are released. I was hoping for that in Nov. 2016, but I guess it will be Sept. 2017.

RHB-104 - Crohn’s disease (Phase III) and multiple sclerosis (Phase IIa)

Crohn’s disease - first Phase III study ongoing

Approximately 200 subjects out of the planned total of 270 have been enrolled to date in the randomized, double-blind, placebo-controlled first Phase III study with RHB-104 for Crohn’s disease (the MAP US study).


Interim data and safety monitoring board (DSMB) analysis is on track to take place in the fourth quarter of 2016 and RedHill remains blinded to the interim and ongoing results.


RedHill is currently reviewing a possible amendment to the Phase III MAP US study protocol intended to further enhance the overall robustness of the study, provide a more precise assessment of RHB-104’s treatment effect, collect additional endoscopic mucosal healing data, further evaluate the Crohn’s disease population enrolled and address retention and early terminations. No changes are planned to the primary endpoint of remission at week 26 or the study’s 90% power. Taking into account a potential protocol amendment, completion of recruitment is expected in 2017 with no anticipated material impact on the Company’s overall cash burn rate through the end of 2017. The Company expects to provide further details in the coming weeks, once plans are finalized.
 
Does anyone here know if doctors in the US risk having their license revoked by treating Crohn's with AMAT? After watching Under Our Skin, about Lyme disease and what happened to some doctors who went against protocol, I was wondering if there is the same risk.

Thank you.
 
So far I haven't heard of any, though I imagine it's a concern to many. I haven't watched the piece on Lyme's, but there's some really decent research and small study data which could justify treatment of CD with AMAT, so that would be in their favor. Also, patients who don't have traditional treatment options left may be more able to get AMAT due to that. I volunteered to my doc that I'd be happy to sign an informed consent and liability waiver, since it would protect her a slight bit more. She only saw it as a formality, since she thiught the research was valid and due to that wasn't worried about the liability. I think the argument could be made that the RedHill trial (being in stage 3 with promising previous stage data) would insulate docs who decide to follow that protocol. At the end of the day though, it's not an approved treatment pathway, and without the large double blinded study, I think docs are more worried about success and risk to the patient vs. the liability issue to themselves. At this point, they just aren't convinced it works.

(Of course, if RedHill turns out successful, starting a tidal wave of funding on research into this theory which eventually conclusivelyproves CD to be zoonotic, there's going to be liability assessed then too. Who knew what, when did they know, why wasn't research funded, etc. But that's a whole different issue!)
 
In this retrospective study, the researchers are theorizing that TB induces an auto-immune reaction to trick the immune system into attacking the lungs which in turn helps its transmission: "...autoimmunity is a critical process exacerbating pathology in TB, leading to cavitation and transmission."

They support their theory by listing diverse autoimmune phenomena that occur in a portion of TB cases. For example, autoantibodies associated
with diseases such as Wegener's granulomatosis and systemic lupus erythematosus is detected in 40% of TB patients. They also point to cases of uveitis and erythema nodosum, which also occurs in some TB cases. Their strongest argument is that TB and Sarcoidosis, an autoimmune disease with no proof of an infectious etiology, are virtually indistinguishable.

Even though this is a theory they've got, given TB and MAP are cousins, this may have some interesting implications for MAP research, at least from a layperson's perspective.
 
Hi,

I was looking at the trial "Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease (MAPUS)" for RHB-104 and noted one of the exclusions was

Presence of active fistulizing Crohn's Disease or healed fistula within 2 months prior to screening.

As someone who is aware of the theory of MAP being associated with causing Crohn's, but not well read, and someone with fistulas, I was wondering if anyone knew why they would exclude these patients from the trial? Mainly I am thinking for the future (if this treatment was proved effective is there something about having a fistula that prevents anti-MAP therapy as an option)?

Not sure if it's something that anyone is going to have an answer for, but I figured it's probably not something I am going to find in a frequently asked questions somewhere regarding the trial.

Cheers,

Cameron
 
Cameron,

My son could not participate for the same reason, and I inquired as to why because AMAT is effective for healing fistulas. The only reason why they exclude fistulas is that having them is considered a separate disease, called Fistulizing Crohn's! Trials are very strict with their criteria and researchers cannot deviate at all from them otherwise they will not get approval. It is very frustrating but unfortunately it is how the process works.

I have faith that it will win approval though...at least I hope so, and at that time you should be able to get on the treatment.
 
Cameron,

My son could not participate for the same reason, and I inquired as to why because AMAT is effective for healing fistulas. The only reason why they exclude fistulas is that having them is considered a separate disease, called Fistulizing Crohn's! Trials are very strict with their criteria and researchers cannot deviate at all from them otherwise they will not get approval. It is very frustrating but unfortunately it is how the process works.

I have faith that it will win approval though...at least I hope so, and at that time you should be able to get on the treatment.
Exactly the information I was looking for, thank you. :thumright:
 
Thanks, it's interesting, but it doesn't say they've made a vaccine, it says:
Davis’ theory linking Crohn’s disease to MAP infections in humans, has driven him to devote a significant part of his career to the development of a vaccine to remove MAP from cattle, and thus from the food supply and the environment.
Regardless of whether or not MAP is causative, “We’re making significant progress on a vaccine,” explained Davis. A cattle vaccine provides the greatest promise for controlling Johne’s disease and benefitting cattle, regardless of the uncertainty surrounding the associations to human Crohn’s disease.
Edit: On second thought, semantically, it's not wrong to infer that they have made a vaccine. My bad. I can't delete this post so I'm editing it instead.
 
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From the case report article:

Dr. Prabhat Agarwal took interest in the case and was willing to consider the patient’s illness could be associated with an extensive infection with MAP. Dr. T. J. Borody, who had reported success in treating patients with CD with antibiotics was contacted for advice and recommendation on how to treat the patient (7). Dr. Borody provided copies of recent publications and suggested what antibiotics should be considered for treatment. Based on his suggestions, a regimen of therapy was designed and implemented. The patient was informed that his clinical symptoms were most likely caused by a MAP infection and that a regimen of antibiotic therapy might provide a cure. After obtaining his written consent, he was placed on anti-MAP therapy under the supervision of Dr. Prabhat Agarwal. The antibiotic therapy included clarithromycin, rifampin, ethambutol, levofloxacin, isoniazid, and rifaximin along with mesalazine according to the schedule in Table 1.
Results
After 4 months of treatment, the patient exhibited improvement in his physical condition, reduction in stool frequency (two to three times a day from every half hour), and improvement in appetite. During the last months of treatment, the patient experienced continued improvement, with an increase in weight and further reduction in stool frequency (one to two times a day). Recovery from infection was complete following a year of treatment with no signs or symptoms of disease. The follow-up stool microscopy was negative for MAP (Figure 2B) and the follow-up post-treatment stool culture was negative for MAP. As mentioned, biotyping of colonies from cultures of stool showed the bacilli were the “Indian Bison type” of MAP (Figure 3). The ELISA was positive for MAP also, further confirmation that the patient had been infected with MAP (Table 2). The patient is now being monitored every 6 months for recurrence of infection and general health.
This case provides additional evidence, supporting studies showing MAP is the causative agent in, at least, a subset of patients with CD (26) and that antibiotic therapy may lead to a cure of CD and clearance of infection with MAP. The results are consistent with findings from a group of MAP infected patients treated successfully by one of the coauthors, Dr. J. Todd Kuenstner, in the United States using a regimen of multi-antibiotic therapy combined with ultraviolet blood irradiation (UVBI) (27, 28). Of major importance, the results obtained in this report and the mass survey in India emphasize the need for recognition, at the international level, that MAP is a zoonotic pathogen and that it is a health risk for humans and livestock (29).
Concurrent Resolution of Chronic Diarrhea Likely Due to Crohn’s Disease and Infection with Mycobacterium avium paratuberculosis
http://journal.frontiersin.org/article/10.3389/fmed.2016.00049/full#B25
 
http://onlinelibrary.wiley.com/doi/10.1111/apt.13840/full

Endoscopic and clinical responses to anti-tubercular therapy can differentiate intestinal tuberculosis from Crohn's disease

In layman's terms, take a group of patients with identical symptoms who live in an area of the world where Tuberculosis is prevalent, but Crohn's is also present. Treat them with anti-Tuberculosis antibiotics and observe their symptoms at regular intervals up to 12 months. The outcome? They roughly divide into three groups:
1) The group with Mycobacterium Tuberculosis infection who recover completely -> ITB
2) The group where their general symptoms improve but they are not cured and they do not achieve mucosal healing -> Crohn's probably caused by MAP
3) The group who show no improvement or their symptoms get worse -> Crohn's caused by ?

The important point though is this, what we call Crohn's has identical symptoms to another mycobacterial infection intestinal Tuberculosis, the only difference is the antibiotics used to treat TB do not kill it off. Further, the group we label as Crohn's has two clear sub-groups based on how they respond to antibiotics, one of which I believe is a MAP infection.

http://onlinelibrary.wiley.com/enhanced/figures/doi/10.1111/apt.13840#figure-viewer-apt13840-fig-0004
 
AIEC is probably the other culprit imo, lots of literature stacking up suggesting so, also seems to be a few therapies targeting AIEC in the works... hopefully between the map vaccine and qu biologic's ssi vaccine we can say goodbye to this horrible condition.
 
New article: Concurrent Resolution of Chronic Diarrhea Likely Due to Crohn's Disease and Infection with Mycobacterium avium paratuberculosis.

https://www.ncbi.nlm.nih.gov/pubmed/27833911

Abstract
Examination of samples of stool from a 61-year-old male patient, presenting with the clinical symptoms of Crohn's disease (CD), revealed massive shedding of acid fast bacilli with the morphology of Mycobacterium avium paratuberculosis (MAP), the causative agent of Johne's disease in cattle. MAP was cultured from the stool. Biotyping of the bacterium isolated from cultures of stool demonstrated, it was the Indian Bison biotype of MAP, the dominant biotype infecting livestock and humans in India. Based on this finding and because the patient was unresponsive to standard therapy used in India to treat patients with gastrointestinal inflammatory disorders, the patient was placed on a regimen of multi-antibiotic therapy, currently used to treat tuberculosis and CD. After 1 year of treatment, the patient's health was restored, concurrent with cessation of shedding of MAP in his stool. This patient is the first case shown to shed MAP from the stool who was cured of infection with antibiotics and who was concurrently cured of clinical signs of CD.
KEYWORDS:
Crohn’s disease; ELISA; IS900 PCR and IS1311 PCR_RE; Mycobacterium avium paratuberculosis; antibiotic therapy; stool culture and microscopy for MAP
 
AIEC is probably the other culprit imo, lots of literature stacking up suggesting so, also seems to be a few therapies targeting AIEC in the works... hopefully between the map vaccine and qu biologic's ssi vaccine we can say goodbye to this horrible condition.
Amen to that.
 
Fingers crossed!

"RedHill's late-stage study of RHB-104 in Crohn's to continue as planned
Dec. 13, 2016 9:21 AM ET|By: Douglas W. House, SA News Editor
Following a pre-planned review, the independent Data and Safety Monitoring Board (DSMB) unanimously recommends that RedHill Biopharma's (NASDAQ:RDHL) Phase 3 clinical trial, MAP US, assessing combination antibiotic RHB-104 for the treatment of Crohn's disease continue as planned without modification. Two additional independent DSMB reviews will take place after 50% and 75% of subjects have completed 26 weeks in the study. The next review should happen in Q2 2017.
According to ClinicalTrials.gov, the estimated final data collection date for the primary endpoint, remission at week 26, is September 2017. The estimated study completion date is April 2018."
 
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