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  • Jefferson Adams
    Jefferson Adams

    Larazotide Acetate in Patients With Celiac Disease Undergoing a Gluten Challenge

    Reviewed and edited by a celiac disease expert.

    Celiac.com 02/04/2013 - Ever wonder what happens to all those celiac disease patients who volunteer to do a gluten-challenge in the name of science? Well, the short answer is that they likely suffer, and may incur gut damage, at least in the short term.

    Photo: CC--CeresBA team of researchers looking for ways to reduce or eliminate that problem recently conducted a study using larazotide acetate, a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated problems.



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    The research team included C. P. Kelly, P. H. R. Green, J. A. Murray, A. DiMarino, A. Colatrella, D. A. Leffler, T. Alexander, R. Arsenescu, F. Leon, J. G. Jiang, L. A. Arterburner, B. M. Paterson, R. N. and Fedorak. They are affiliated with the Celiac Center of Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, the Celiac Disease Center at Columbia University in New York, NY, the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, MN, Thomas Jefferson University Hospital in Philadelphia, PA, the Pittsburgh Gastroenterology Associates in Pittsburgh, PA, with Gastrointestinal Specialists of Troy, MI, the Department of Internal Medicine at the University of Kentucky, in Lexington, KY, with Alba Therapeutics Corporation in Baltimore, MD, and with the Division of Gastroenterology at the University of Alberta in Edmonton, AB.

    The team wanted to find out how well larazotide acetate worked and how well it was tolerated by celiac disease patients undergoing a gluten challenge.

    To do this, the team conducted an exploratory, double-blind, randomized, placebo-controlled study that included 184 patients who maintained a gluten-free diet before and during the study.

    After a gluten-free diet run-in, the team randomly divided patients into groups and gave them either larazotide acetate in doses of 1, 4, or 8 mg three times daily, or a placebo. Both groups also received 2.7 grams of gluten daily for six weeks.

    The team then assessed ratios of lactulose-to-mannitol (LAMA), an experimental biomarker of intestinal permeability, and measured clinical symptoms by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels.

    They found no significant differences in LAMA ratios between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo).

    They did find that the average ratio of anti-tissue transglutaminase IgA levels was 19.0 over baseline in the placebo group compared with 5.78 (P = 0.010) in the 1mg larazotide acetate group, 3.88 (P = 0.005) in the 4mg larazotide acetate group, and 7.72 (P = 0.025) in the 8mg larazotide acetate group.

    Both the larazotide acetate and placebo groups showed similar rates of "adverse events."

    Overall, the team found that larazotide acetate reduced gluten-induced immune reactivity and symptoms in celiac disease patients undergoing gluten challenge and was generally well tolerated.

    However, the team found no significant difference in LAMA ratios between the larazotide acetate and placebo groups.

    Even though they did not find anything revolutionary, the results and design of their study will likely be helpful in shaping future gluten-challenge studies in patients with celiac disease.

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    I am glad someone has written something about this study. Many had high hopes for this. It was too good to be true. I have been following Dr. Fasano's papers and the last one in 2011 where he says that he believe that all autoimmunity is not auto perpetuating once you can remove the environmental triggers, stuff we swallow etc., then it can be stopped. I would suggest that Ketogenic diet and testing back paleo type carbs is the best we got unless you want to risk autoimmune suppressing drug alternatives which is a really really bad idea.

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  • About Me

    Jefferson Adams

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.


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    Jefferson Adams
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    Celiac.com 05/23/2007 - The results of a study recently published in the journal Gut indicate that some people who suffer from celiac disease might not need to remain on a gluten free diet for their entire lives, and that some celiac patients might be able to safely introduce gluten containing foods without suffering a relapse.
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    Results Show 20% Long-term Latency in Celiac Patients who Eat Normal Diet
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    (3) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pathology, Paris, France.
    (4) INSERM, Equipe Avenir, Faculté de Médecine René Descartes, Paris, France.
    (5) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pediatric Gastroenterology, Paris, France.
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    Comments on this Study by Ron Hoggan
    This is dressed up like a new finding, but it isn't. There are a number of studies that show similar findings. Part of that problem lies in the interpretation of the biopsies, and part of the problem arises out of failing to recognize the variable nature of the disease. It has long been known to wax and wane for reasons beyond our ken. Samuel Gee (1888) and Gibbons (1889) both reported the cyclic nature of their patients symptoms. They cited a study to support the idea of a two year rule saying that relapse would usually occur within two years, yet Kuitunen P, Savilahti E, Verkasalo M., in Late mucosal relapse in a boy with coeliac disease and cows milk allergy. Acta Paediatr Scand. 1986 Mar;75(2):340-2. reported one patient who at 4.3 years on a normal diet showed normal villous architecture. It was not until a follow-up biopsy at more than 8 years of eating a gluten-containing diet that he showed villous atrophy. These findings, along with all the other studies that have shown long delays in some patients before relapsing, argue strongly for Michael N. Marsh's position that we should concentrate on treating any immune system that is sensitized to gluten with a gluten-free diet. His rectal challenge is an excellent tool for identifying such sensitized immune systems. Dr. Fines fecal antibody test probably fits into the same category. The underlying assumption is that the biopsy will identify all cases of intestinal lesion regardless of the possibility of patchy lesions that are well documented in the literature. They deal with increased IEL counts as if they were a feature of latent celiac disease when that is not the case. There are several other points on which this study falters. They admit that the latency can be transient. Unfortunately, they have not exchanged emails with people where they have returned to eating gluten and have developed an abdominal cancer. I exchanged emails with such a young man who blamed himself for having killed himself with his carelessness about his diet. How awful that was for him! Yet these authors seem to think it is quite acceptable for patients to indulge during their latency periods and only consider a diet if there is a relapse of intestinal lesion.
     


    Jefferson Adams
    Celiac.com 04/18/2012 - Biopharmaceutical development company, BioLineRx, has announced results from pre-clinical trials which show that their compound, BL-7010, an orally available treatment for celiac disease, reduces the toxic effects of gluten in patients with celiac disease.
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    http://www.news-medical.net/news/20120222/BioLineRx-BL-7010-may-reduce-gluten-toxicity-in-patients-with-celiac-disease.aspx


    Jefferson Adams
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    Scand J Gastroenterol. 2012 Apr 23.


    Jefferson Adams
    Celiac.com 12/03/2012 - Gluten sensitivity has recently been added to the spectrum of gluten-related disorders, but precise diagnostic markers do not yet exist. A research team recently set out to understand the blood test pattern of gluten sensitivity, and to compare it with the blood test pattern seen in celiac disease.
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    Source:
    J Clin Gastroenterol. 2012 Sep;46(8):680-5.


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