Probiotic BL NCC 2705 and Gluten Sensitivity

Study Overview
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Brief Summary
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The aim of the study is to confirm/prove safety of the probiotic and production of serpin in humans.

Detailed Description
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This trial is a multicenter, double blind, randomized, placebo controlled, 2 by 2 cross-over design (i.e. 2-sequences, 2-periods, 2-treatments) for each specific population (i.e. self-reported Non Coeliac Gluten Sensitivity and Coeliac Disease subjects). 1 capsule of BL NCC 2705 or placebo will be given twice a day in the morning and in the evening with a meal over 2 periods of 4 days. On day four a single dose of gluten (3g) will be administered and duodenal fluid will be collected in the following hours through a naso-intestinal catheter. The viability of BL NCC 2705, the production of serpin and its effects on gluten digestion and intestinal enzymatic activity will be determined. No chronic administration of gluten as a challenge is foreseen in the study. After a wash out period of minimum 2 weeks, period will be repeated.

Official Title
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Proof of Concept Clinical Trial of Safety and Biological Activity of Bifidobacterium Longum NCC 2705 in Gluten Sensitivity

Conditions
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Celiac Disease, Non-celiac Gluten Sensitivity

Intervention / Treatment
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* Dietary Supplement: Intervention 1 : BL NCC 2705 + Maltodextrin
* Other: Intervention 1 : Maltodextrin
* Dietary Supplement: Intervention 2 : BL NCC 2705 + Maltodextrin
* Other: Intervention 2 : Maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to sign written informed consent prior to trial entry Male or female adults >18 years of age For NCGS: self-reported gluten sensitivity with negative CD serology, on gluten free diet for at least 6 weeks with self-reported significant symptomatic improvement For CD: confirmed serologic and histologic diagnosis of CD and on GFD for at least 12 months with self-reported significant symptomatic improvement Body Mass Index (BMI) within the range >18 - <30 kg/m2 Willing and able to comply with study procedures and restrictions In good health as determined by a medical history and medical examination Exclusion Criteria: Documented IgE-mediated food allergy Subjects following an overly imbalanced or restrictive diet as per nutritional advice Concurrent systemic disease and/or laboratory abnormalities considered by investigators to be detrimental for the participants safety or potentially interfering with the study procedures and/or study outcomes Concurrent organic GI pathology other than benign polyps, diverticulosis, hemorrhoids, lipomas and melanosis coli Previous abdominal surgery with the exception of hernia repair, appendectomy, caesarian section, tubal ligation, hysterectomy, hemorrhoidectomy Patients who received antibiotics in the previous 2 weeks women of childbearing potential not willing to use an effective contraception method

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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Period 1: Placebo - Period 2: BL NCC 2705<br>For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity) | Other: Intervention 1 : Maltodextrin<br>* 2 capsules of Placebo/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of Placebo in the morning of the 4th day<br>Dietary Supplement: Intervention 2 : BL NCC 2705 + Maltodextrin<br>* 2 capsules of BL NCC 2705/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of BL NCC 2705 in the morning of the 4th day<br>|
| Other: Period 1: BL NCC 2705 - Period 2: Placebo<br>For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity) | Dietary Supplement: Intervention 1 : BL NCC 2705 + Maltodextrin<br>* 2 capsules of BL NCC 2705/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of BL NCC 2705 in the morning of the 4th day<br>Other: Intervention 2 : Maltodextrin<br>* 2 capsules of Placebo/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of Placebo in the morning of the 4th day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence, type and severity of adverse event | incidence, type and severity of adverse event | from Baseline to end of study (up to maximum 43 days) | 
| Gastro-intestinal tolerability: visual analog scale | Sum of visual analog scale for gastro-intestinal symptoms assessment (nausea, vomiting, diarrhea, audible bowel sound, flatulence and abdominal cramping symptoms are assessed). Each scale is from 0 (no symptom) to 100mm (maximum symptom). The maximum sum value is 600. | from Baseline to end of study (up to maximum 43 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of bacterial Serpin RNA and/or proteins (ng/mL) in duodenal aspirates | Measurements via RT-PRC and immuno-assay | 19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36) | 
| Concentration of Probiotic BL NCC 2705 (ng/mL) in duodenal aspirates | Measurements via PCR | 19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36) | 
| Concentration of gluten derived pepides in duodenal aspirates | Effect of BL NCC 2705 on gluten digestion based on the amount of gluten peptides detected in duodenal apsirates | 10 sampling over 3h30 at visit 2 (day 4) and visit 3 (from day 22 to day 36) | 
| Concentration of gluten derived pepides in urine | Effect of BL NCC 2705 on gluten digestion based on the amount of gluten peptides detected in urine | 10 sampling over 3h30 at visit 2 (day 4) and visit 3 (from day 22 to day 36) | 
| Level of elastase (Units/ mL) activity in duodenal aspirates | Measurements of proteolytic activity based assay | 19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36) |