Celiac Disease and Vitamin Status: Evaluation of the Effect of Supplementation With a Probiotic (VIVOMIXX®) in a Cohoort of Celiac Patients (VIVOMIXX)

Celiac Disease and Vitamin Status: Evaluation of the Effect of Supplementation With a Probiotic (VIVOMIXX®) on Vitamin B6, B12, 25'OH D, Folic Acid and Omocystein Levels, Metabolic and Inflammatory Status, and Gut Microbiota Metabolomics in a Cohoort of Celiac Patients

Celiac disease is a disorder caused by a disregulation of the immune system which leads to immune response to gluten. Diet therapy is the gold standard of treatment, and the only effective one. Macronutrients and micronutrients deficiency (vitamin D, folic acid, vitamin B12, vitamin B6, iron and zinc), which is in any case far more common in patients who don't follow gluten free diet, can persist in a subset of patients who follow gluten-free diet. Supplementation of vitamins in these patients may have a beneficial role. A recent study in a murine model showed that supplementation with probiotic VIVOMIXX® leads to an increase in expression of vitamin D receptors in proximal and distal colon.

This is an interventional controlled randomized double blind study, which evaluates the effect of VIVOMIXX® on vitamin status.

Study Overview

• Status: Recruiting
• Conditions: Celiac Disease
• Intervention / Treatment: Drug: Probiotic Vivomixx; Behavioral: Gluten free diet; Other: Placebo

Detailed Description

90 patients with celiac disease who follow gluten free diet will be enrolled. INCLUSION CRITERIA

• Celiac disease (diagnosis made according to ESPGHAN criteria) EXCLUSION CRITERIA
• Supplementation with pre/probiotics in the previous 3 months;
• Antibiotic therapy in the previous 3 months;
• Comorbidity with other acute (in the previous 3 months) or chronic gastrointestinal disorders
• Supplementation with group B vitamins for any reason

Patients enrolled will be referred to Paediatric Gastroenterology Service in San Paolo Hospital at the time of enrollement (T0) and after intervention therapy (T1, + 4 months).

Patients will be randomized in one of the two arms of intervention (VIVOMIXX once a day for 4 months versus placebo once a day for 4 months).

VIVOMIXX® is a probiotic containing 8 differenct strains of bacteria: Streptococcus thermophilus DSM 24731, bifidobacteria (B. breve DSM 24732, B. longum DSM 24736, B. infantis DSM 24737) lactobacilli (L. acidophilus DSM 24735, L. plantarum DSM 24730, L. paracasei DSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734). Every sachet contains 450 billions of bacteria, maltose and silicon dioxide. VIVOMIXX® will be freely given by the society MENDES S.A. - Lugano Switzerland.

At each time point clinic evaluation, nutritional assessment and blood testing will be made. Data collection will include:

• Systemic arterial blood pressure;
• Anthropometric measures (height, weight, body mass index, waist circumference, triceps skinfold)
• Clinical evaluation including presence/absence of oral aphtous stomatitis
• Measure of chinolinic acid, serotonin, ghrelin (analysis will be made at Istituto Malattie Infettive, Università La Sapienza, Roma).
• Dosing of inflammatory markers (analysis will be made at Health Sciences Department, San Paolo Hospital).
• Metabolomics on stool samples (analysis will be made at Bologna University, Dipartimento di Scienze e Tecnologie Agro-Alimentari, Cesena, with a financial fund by MENDES S.A. - Lugano Switzerland).
• Routine blood testing including complete blood cell count, vitamin B6, acid folic, vitamin B12, vitamin D 25'OH, fasting glucose, fasting insulin, total cholesterol, LDL and HDL cholesterol, Apolipoprotein A1 and Apolipoprotein B, triglycerides, homocistein, auto-antibody anti endomisium and anti-transglutaminase,
• Genetic testing for MTHFR gene
• ESR, highly sensitive CRP, IL6, TNFalfa, fibrinogen
• Fecal calprotectin.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20142
    • Recruiting
    • Ospedale San Paolo
    • Contact: Elvira Verduci, MD PhD Assistant Professor; Phone Number: +39 0281844508; Email: elvira.verduci@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Celiac disease (diagnosis made according to European Society for Paediatric Gastroenterology Hepatology and Nutrition)

Exclusion Criteria:

• Supplementation with pre/probiotics in the previous 3 months;
• Antibiotic therapy in the previous 3 months;
• Comorbidity with other acute (in the previous 3 months) or chronic gastrointestinal disorders
• Supplementation with group B vitamins for any reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Behavioral: Gluten free diet; Gluten free diet will be encouraged in both arms; Other: Placebo; Placebo with same taste than VIVOMIXX, containing maltose and silicon dioxide once a day for 4 months.
Active Comparator: Probiotic	Drug: Probiotic Vivomixx; VIVOMIXX once a day for 4 months. VIVOMIXX® is a probiotic containing 8 differenct strains of bacteria: Streptococcus thermophilus DSM 24731, bifidobacteria (B. breve DSM 24732, B. longum DSM 24736, B. infantis DSM 24737) lactobacilli (L. acidophilus DSM 24735, L. plantarum DSM 24730, L. paracasei DSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734). Every sachet contains 450 billions of bacteria, maltose and silicon dioxide. VIVOMIXX® will be freely given by the society MENDES S.A. - Lugano Switzerland.; Behavioral: Gluten free diet; Gluten free diet will be encouraged in both arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in vitamin B6, folic acid, vitamin B12 and 25'OH vitamin D levels in blood	Time point 0: day 0 Time point 1: after 4 months
Changes in homocysteine levels in blood	Time point 0: day 0 Time point 1: after 4 months
Changes in ghrelin, chinolinic acid and serotonin levels	Time point 0: day 0 Time point 1: after 4 months
Changes in fecal metabolomics (including production of short chain fatty acids verified by gas-chromatography)	Time point 0: day 0 Time point 1: after 4 months
Changes in highly sensitive C reactive protein levels	Time point 0: day 0 Time point 1: after 4 months
Changes in erythrocite sedimentation rate	Time point 0: day 0 Time point 1: after 4 months
Changes in fibrinogen blood levels	Time point 0: day 0 Time point 1: after 4 months
Changes in IL-6 blood levels	Time point 0: day 0 Time point 1: after 4 months
Changes in Tumor Necrosis Factor alfa blood levels	Time point 0: day 0 Time point 1: after 4 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in body mass index	Time point 0: day 0 Time point 1: after 4 months
Changes in systemic arterial systolic and diastolic blood pressure	Time point 0: day 0 Time point 1: after 4 months
Changes in height	Time point 0: day 0 Time point 1: after 4 months
Changes in weight	Time point 0: day 0 Time point 1: after 4 months
Changes in waist circumference	Time point 0: day 0 Time point 1: after 4 months
Entity of reduction of triceps skinfold thickness	Time point 0: day 0 Time point 1: after 4 months
Changes in prevalence of aphtous stomatitis	Time point 0: day 0 Time point 1: after 4 months
Changes in chinolinic acid, serotonin, ghrelin levels in blood	Time point 0: day 0 Time point 1: after 4 months
Changes in complete cell blood count	Time point 0: day 0 Time point 1: after 4 months
Changes in total cholesterol levels	Time point 0: day 0 Time point 1: after 4 months
Changes in HDL cholesterol levels	Time point 0: day 0 Time point 1: after 4 months
Changes in LDL cholesterol levels	Time point 0: day 0 Time point 1: after 4 months
Changes in triglycerides levels	Time point 0: day 0 Time point 1: after 4 months
Changes in Apolipoprotein A1 levels	Time point 0: day 0 Time point 1: after 4 months
Changes in Apolipoprotein B levels	Time point 0: day 0 Time point 1: after 4 months
Changes in fasting glucose levels	T0 T1 (+4 months)
Changes in fasting insulin levels	Time point 0: day 0 Time point 1: after 4 months
Changes in auto-antibody anti endomisium titer	Time point 0: day 0 Time point 1: after 4 months
Changes in auto-antibody anti-transglutaminase titer	Time point 0: day 0 Time point 1: after 4 months
Changes in fecal calprotectin levels	Time point 0: day 0 Time point 1: after 4 months
Prevalence of wildtype allele of MTHFR gene by gene sequencing	Time point 0: day 0 (at the enrollement)

Collaborators and Investigators

• Sponsor: University of Milan

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2019
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 9, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): February 10, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Gut microbiota; Celiac disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: 2015/ST/135-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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