Clinical Trial on the Effects of Bifidobacterium Infantis in Active Celiac Disease

Study Overview
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Brief Summary
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This exploratory study has been designed to determine the effect of the probiotic Bifidobacterium infantis vs. placebo orally administered over a period of 3 weeks on clinical features, Quality of Life parameters (QoL), intestinal permeability and inflammatory markers of patients having positive serological evidences of Celiac Disease.

Detailed Description
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Objective: This exploratory study has been designed to determine the effect of the probiotic Bifidobacterium infantis vs. placebo orally administered over a period of 3 weeks on clinical features, Quality of Life parameters (QoL), intestinal permeability and inflammatory markers of patients having serological evidences of CD (positive serological markers). The testing period will be approximately three weeks between the results of serological testing and before the intestinal biopsy procedure during which time subjects are consuming a gluten-containing diet. Study Design: A 3-weeks duration, placebo-controlled, double-blind, randomized study plan in ambulatory (non-hospitalized outpatients) patients, with 2 parallel groups. Treatment arms will be as follows: A). Placebo 2 capsules 3 times daily (morning, evening and night). B). Probiotics (Bifidobacterium infantis) 2 capsules 3 times per day (morning, evening and night).

Official Title
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Exploratory, Randomized, Double-blind, Placebo-Controlled Study on the Effects of Bifidobacterium Infantis in Active Celiac Disease

Conditions
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Celiac Disease

Intervention / Treatment
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* Dietary Supplement: Probiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signing the Informed consent. Men or women, 18-75 years old. BMI between 18.5 and 35. Patients shall have a positive CD-related serology (combined positivity of DGP/tTG Screen plus IgA anti-tTG and or IgA a-DGP tests). Patients will abstain from taking medications prohibited by the study from the 7 days prior the enrolment to the end of the trial: NSAIDs, aspirin, lactulose, probiotics and prebiotics in any form of administration (eg. Yogurts or other dairy products).. Alcohol consumption is prohibited during the same period. Patients should commit to attend on scheduled days, in accordance with the study calendar. To be interested in participating the trial Exclusion Criteria: Patients with refractory CD or severe complications thereof, enteropathy-associated T-cell Lymphoma (EATL), ulcerative jejunitis, perforation, severe osteoporosis, malnutrition, among others. Individuals with symptoms suggestive of lymphoma or any other serious CD complication taking special care in recently-diagnosed patients, 50 years old or older, in whom EATL must be ruled out by standard methods. Individuals with other active chronic GI pathologies like Crohn's disease, ulcerative colitis and irritable bowel syndrome, microscopic colitis, and lactose intolerance. Patients with Type 1 or Type 2 diabetes or other autoimmune diseases, such as autoimmune hepatitis and primary biliary cirrhosis. Individuals with co-morbidities whose participation, in the investigator's judgment, would be inadvisable; for instance, unstable clinical conditions such as chronic obstructive pulmonary disease, angina pectoris, severe cardio-respiratory conditions, etc. Individuals with symptomatic neurological or psychiatric conditions that could potentially interfere with the study. Individuals with a clinical severity requiring immediate treatment at the consideration of the investigator. Patients with hemoglobin levels less than 8.5 g/dL or who had donated blood in the last 56 days or donated a unit of plasma in the last 7 days. Patients with a history of alcohol or drug abuse in the prior 2 years. Individuals taking prohibited medications in relation to the study (see point 6, previous section). Individuals with a history of neoplasia. Individuals participating in another clinical study that either involves medications or concluded during the last 30 days. Individuals previously exposed to Bifidobacteria species. Subjects not willing to maintain a gluten-containing diet during the 3-weeks period of the trial Pregnant women. Allergies to goat milk; no recent or planned dietary changes, esp. regarding gluten intake.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Probiotic<br>* Bifidobacterium infantis, 2 capsules (2.0E+9 CFU/capsule) 3 times/day for a total of 1.2E+10 CFU/day for 21 days.<br>* Other names: Bifidobacterium infantis;|
| Experimental: Probiotic<br>Life Start Two | Dietary Supplement: Probiotic<br>* Bifidobacterium infantis, 2 capsules (2.0E+9 CFU/capsule) 3 times/day for a total of 1.2E+10 CFU/day for 21 days.<br>* Other names: Bifidobacterium infantis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal permeability changes | Subjects will come to the laboratory after an overnight fast, ingest the sugar probes, and collect all urine passed over the ensuing 24 hours into a pre-weighed container with 5 ml of 10% thymol in isopropanol. Urine will be vigorously mixed, total volume recorded, and aliquots rapidly frozen for subsequent transport and analysis. To evaluate intestinal permeability, subjects will ingest a solution containing: 5 g lactulose (Technilab, Montreal, Quebec, Canada), and 2 g mannitol (Sigma, St Louis, Missouri, USA) in 450 ml of water (osmolality approximately 1800 mOsmol/l). | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the cytokine profile. | Mononuclear cells obtained from blood will be isolated by Ficoll-Hypaque density centrifugation and resuspended in complete media/Dulbecco's modified Eagle medium. These mononuclear cells will be termed peripheral blood mononuclear cells (PBMCs). PBMCs will be incubated, nonstimulated, for 72 hours at 37°C in a 5% CO2 humidified atmosphere. Nonstimulated PBMC cytokine reflects the cytokine milieu from wich the PBMCs were originally isolated. Interleukin(IL)-10 and IL-12p40 cytokine levels will be measured using enzyme-linked immunosorbent assays. | 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease, Coeliac Disease