Rifaximin for the Treatment of Persistent Symptoms in Patients With Celiac Disease

Study Overview
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Brief Summary
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Celiac disease is a condition in which the small intestine is damaged by gluten, the storage protein of wheat and similar proteins in barley and rye. The disease can cause different symptoms such as diarrhea, bloating, abdominal pain and weight loss. The majority of patients respond to a gluten-free diet. However some patients (5-30%) have persistent symptoms and are considered to be poor responders to the diet. Bacterial overgrowth in the small intestine accounts for some of the refractory patients. This study seeks to determine if antibiotic therapy with rifaximin relieves the symptoms of patients who are poorly responsive to a gluten-free diet and whether this impacts their breath test results.

Detailed Description
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A symptom questionnaire will be administered at study initiation, 2 weeks and 12 weeks. Patients will undergo a breath test which involves drinking a sugar (lactulose) solution and breathing into a machine. This technique will identify the presence of bacteria in the small intestine. They will be randomly selected to receive either an antibiotic (rifaximin) or placebo three times a day for 10 days to treat their bacterial overgrowth.

Official Title
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Double-blind Randomized Controlled Trial of Rifaximin for Persistent Symptoms in Patients With Celiac Disease

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: Rifaximin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients age 18 or older Biopsy proven celiac disease Persistent symptoms of diarrhea, gas, bloating and/or cramping despite a gluten free diet for at least 1 month Women that are not pregnant or lactating can be included. All women must have a documented negative pregnancy test at the initiation of the study. Women who become pregnant during the study will be asked to discontinue the study drug and will be followed up until the outcome of pregnancy is known. Women of child bearing potential must be practicing an effective method of birth control (eg: prescription oral contraceptive, contraceptive injections, intra-uterine device (IUD), double barrier method, contraceptive patch, male sterilization) before entry and throughout the treatment period. Exclusion Criteria: antibiotic use for any indication within preceding one month use of bismuth compounds within preceding month concomitant use of pancreatic supplements concomitant use of antispasmodics concomitant use of immunomodulators such as corticosteroids, budesonide, alkylating agents and antimetabolites. concomitant use of probiotics concomitant use of prokinetic agents concomitant use of 5-hydroxytryptamine receptor (5HT3) antagonists,5-hydroxytryptamine receptor (5HT4) antagonists. concomitant use of antimotility agents (e.g loperamide) concomitant use of antidiarrheal agents diagnosed microscopic colitis or inflammatory bowel disease other causes of malabsorption: pancreatic insufficiency, giardiasis and enteropathy associated with T cell lymphoma. other diseases: renal or hepatic insufficiency. pregnant patients and lactating females. In addition women of child bearing age will be excluded if they are not using one of the methods of contraception like oral contraceptives,intrauterine device. and double barrier methods. patients with tuberculosis or a positive purified protein derivative (PPD) test and infection with other mycobacterial diseases. allergy and/or potential emergence of drug resistance to rifampicin and rifamycin compounds.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rifaximin 400mg<br>Antibiotic ,Rifaximin 400mg, given 3 times a day for 10 days. | Drug: Rifaximin<br>* Rifaximin 400mg orally three times a day for 10 days total<br>* Other names: Placebo orally three times a day for 10 days total;|
| Placebo Comparator: Placebo<br>Placebo pills given 3 times a day for 10 days. | Drug: Placebo<br>* Placebo orally three times a day for 10 days total<br>* Other names: Rifaximin 400 mg orally three times a day for 10 days total;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Gastrointestinal Symptom Rating Scale (GSRS) Score | Validated seven point questionnaire that assesses gastrointestinal symptoms for five symptom areas, including abdominal pain, reflux, indigestion, diarrhea, and constipation. Individual scores are calculated for each symptom area and the mean of the scores is used to derive an overall GSRS score. Scores range from 0-7, with higher scores indicating gastrointestinal discomfort. | Baseline (week 0) | 
| Week 2 Gastrointestinal Symptom Rating Scale (GSRS) Score | Validated seven point questionnaire that assesses gastrointestinal symptoms for five symptom areas, including abdominal pain, reflux, indigestion, diarrhea, and constipation. Individual scores are calculated for each symptom area and the mean of the scores is used to derive an overall GSRS score. Scores range from 0-7, with higher scores indicating gastrointestinal discomfort. | Week 2 | 
| Week 12 Gastrointestinal Symptom Rating Scale (GSRS) Score | Validated seven point questionnaire that assesses gastrointestinal symptoms for five symptom areas, including abdominal pain, reflux, indigestion, diarrhea, and constipation. Individual scores are calculated for each symptom area and the mean of the scores is used to derive an overall GSRS score. Scores range from 0-7, with higher scores indicating gastrointestinal discomfort. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Abnormal Breath Test | A breath test measures for small intestine bacterial overgrowth (SIBO). The breath test measures the amount of hydrogen exhaled after drinking a sugar (lactulose) solution. An abnormal breath test is defined as: 1) a rise in hydrogen of ≥20 parts per million (ppm) within 100 minutes, or 2) two peaks ≥20 ppm over baseline. | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory, Gastrointestinal Symptom Rating Scale (GSRS), Poorly responsive, Small intestine bacterial overgrowth, Breath test