Celiac Disease
Conditions
Keywords
Gastrointestinal Symptom Rating Scale (GSRS), Poorly responsive, Refractory, Small intestine bacterial overgrowth, Breath test
Brief summary
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
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.
Interventions
DRUGRifaximin
Rifaximin 400mg orally three times a day for 10 days total
DRUGPlacebo
Placebo orally three times a day for 10 days total
Sponsors
Bausch Health Americas, Inc.
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
1. antibiotic use for any indication within preceding one month 2. use of bismuth compounds within preceding month 3. concomitant use of pancreatic supplements 4. concomitant use of antispasmodics 5. concomitant use of immunomodulators such as corticosteroids, budesonide, alkylating agents and antimetabolites. 6. concomitant use of probiotics 7. concomitant use of prokinetic agents 8. concomitant use of 5-hydroxytryptamine receptor (5HT3) antagonists,5-hydroxytryptamine receptor (5HT4) antagonists. 9. concomitant use of antimotility agents (e.g loperamide) 10. concomitant use of antidiarrheal agents 11. diagnosed microscopic colitis or inflammatory bowel disease 12. other causes of malabsorption: pancreatic insufficiency, giardiasis and enteropathy associated with T cell lymphoma. 13. other diseases: renal or hepatic insufficiency. 14. 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. 15. patients with tuberculosis or a positive purified protein derivative (PPD) test and infection with other mycobacterial diseases. 16. allergy and/or potential emergence of drug resistance to rifampicin and rifamycin compounds.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Gastrointestinal Symptom Rating Scale (GSRS) Score | Baseline (week 0) | 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 Gastrointestinal Symptom Rating Scale (GSRS) Score | Week 2 | 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 Gastrointestinal Symptom Rating Scale (GSRS) Score | Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Abnormal Breath Test | Up to 12 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Recruited from Celiac Disease Center.
Pre-assignment details
Fifty participants were enrolled and 41 participants completed the trial.
Participants by arm
| Arm | Count |
|---|---|
| Rifaximin Antibiotic ( 25 subjects) 400 mg capsules of Rifaximin 3 times a day for 10 days. | 25 |
| Placebo Inert capsules ( 25 Subjects) Placebo capsules 3 times a day for 10 days. | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Placebo | Rifaximin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Age, Continuous | 43.4 years STANDARD_DEVIATION 14 | 41.9 years STANDARD_DEVIATION 14.6 | 42.7 years STANDARD_DEVIATION 14 |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
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.
Time frame: Baseline (week 0)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rifaximin | Baseline Gastrointestinal Symptom Rating Scale (GSRS) Score | 2.7 Score on a scale | Standard Deviation 1.1 |
| Placebo | Baseline Gastrointestinal Symptom Rating Scale (GSRS) Score | 2.8 Score on a scale | Standard Deviation 0.9 |
Primary
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.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rifaximin | Week 12 Gastrointestinal Symptom Rating Scale (GSRS) Score | 2.5 score on a scale | Standard Deviation 0.8 |
| Placebo | Week 12 Gastrointestinal Symptom Rating Scale (GSRS) Score | 2.5 score on a scale | Standard Deviation 0.8 |
Primary
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.
Time frame: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rifaximin | Week 2 Gastrointestinal Symptom Rating Scale (GSRS) Score | 2.3 score on a scale | Standard Deviation 0.6 |
| Placebo | Week 2 Gastrointestinal Symptom Rating Scale (GSRS) Score | 2.4 score on a scale | Standard Deviation 0.6 |
Secondary
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.
Time frame: Up to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rifaximin | Percentage of Participants With Abnormal Breath Test | 12 Percent of Participants |
| Placebo | Percentage of Participants With Abnormal Breath Test | 20 Percent of Participants |