Probiotic BL NCC 2705 and Gluten Sensitivity

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

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

Study Overview

• Status: Completed
• Conditions: Celiac Disease; Non-celiac Gluten Sensitivity
• Intervention / Treatment: Other: Intervention 1 : Maltodextrin; Dietary supplement: Intervention 2 : BL NCC 2705 + Maltodextrin; Dietary supplement: Intervention 1 : BL NCC 2705 + Maltodextrin; Other: Intervention 2 : Maltodextrin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Venlo, Netherlands
    • VieCuri Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing and able to sign written informed consent prior to trial entry
2. Male or female adults >18 years of age
3. 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
4. For CD: confirmed serologic and histologic diagnosis of CD and on GFD for at least 12 months with self-reported significant symptomatic improvement
5. Body Mass Index (BMI) within the range >18 - <30 kg/m2
6. Willing and able to comply with study procedures and restrictions
7. In good health as determined by a medical history and medical examination

Exclusion Criteria:

1. Documented IgE-mediated food allergy
2. Subjects following an overly imbalanced or restrictive diet as per nutritional advice
3. 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
4. Concurrent organic GI pathology other than benign polyps, diverticulosis, hemorrhoids, lipomas and melanosis coli
5. Previous abdominal surgery with the exception of hernia repair, appendectomy, caesarian section, tubal ligation, hysterectomy, hemorrhoidectomy
6. Patients who received antibiotics in the previous 2 weeks
7. women of childbearing potential not willing to use an effective contraception method

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Period 1: Placebo - Period 2: BL NCC 2705; For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity)	Other: Intervention 1 : Maltodextrin; 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; Dietary supplement: Intervention 2 : BL NCC 2705 + Maltodextrin; 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
Other: Period 1: BL NCC 2705 - Period 2: Placebo; For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity)	Dietary supplement: Intervention 1 : BL NCC 2705 + Maltodextrin; 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; Other: Intervention 2 : Maltodextrin; 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Nestlé
• Investigators: Study Director: Carmine D'Urzo, Dr., Nestec Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2018
• Primary Completion (Actual): October 4, 2019
• Study Completion (Actual): December 15, 2020

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): December 23, 2020
• Last Update Submitted That Met QC Criteria: December 22, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Immune System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Hypersensitivity; Celiac Disease
• Other Study ID Numbers: 17.11.NRC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No