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

Celiac Disease Clinical Trial

— VIVOMIXX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04160767
• Other study ID #: 2015/ST/135-3
• Status: Recruiting
• Phase: Phase 4
• Start date: January 30, 2019
• Est. completion date: July 2021

Study information

• Verified date: February 2021
• Source: University of Milan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: July 2021
• Est. primary completion date: July 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Celiac Disease

Intervention

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

Other:
• Placebo
Placebo with same taste than VIVOMIXX, containing maltose and silicon dioxide once a day for 4 months.

Locations

Country	Name	City	State
Italy	Ospedale San Paolo	Milan

Sponsors (1)

Lead Sponsor	Collaborator
University of Milan

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Changes in homocysteine levels in blood		Time point 0: day 0 Time point 1: after 4 months
Primary	Changes in ghrelin, chinolinic acid and serotonin levels		Time point 0: day 0 Time point 1: after 4 months
Primary	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
Primary	Changes in highly sensitive C reactive protein levels		Time point 0: day 0 Time point 1: after 4 months
Primary	Changes in erythrocite sedimentation rate		Time point 0: day 0 Time point 1: after 4 months
Primary	Changes in fibrinogen blood levels		Time point 0: day 0 Time point 1: after 4 months
Primary	Changes in IL-6 blood levels		Time point 0: day 0 Time point 1: after 4 months
Primary	Changes in Tumor Necrosis Factor alfa blood levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in body mass index		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in systemic arterial systolic and diastolic blood pressure		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in height		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in weight		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in waist circumference		Time point 0: day 0 Time point 1: after 4 months
Secondary	Entity of reduction of triceps skinfold thickness		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in prevalence of aphtous stomatitis		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in chinolinic acid, serotonin, ghrelin levels in blood		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in complete cell blood count		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in total cholesterol levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in HDL cholesterol levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in LDL cholesterol levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in triglycerides levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in Apolipoprotein A1 levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in Apolipoprotein B levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in fasting glucose levels		T0 T1 (+4 months)
Secondary	Changes in fasting insulin levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in auto-antibody anti endomisium titer		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in auto-antibody anti-transglutaminase titer		Time point 0: day 0 Time point 1: after 4 months
Secondary	Changes in fecal calprotectin levels		Time point 0: day 0 Time point 1: after 4 months
Secondary	Prevalence of wildtype allele of MTHFR gene by gene sequencing		Time point 0: day 0 (at the enrollement)