Clinical trial NCT04160767: Celiac Disease and Vitamin Status: Evaluation of the Effect of Supplementation With a Probiotic (VIVOMIXX®) in a Cohoort of Celiac Patients
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Celiac Disease
Keywords: Celiac disease
Gut microbiota
Lead sponsor: University of Milan
Sponsor class: OTHER
First posted: 2019-11-13
Enrollment: 90
Sex: MALE
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in vitamin B6, folic acid, vitamin B12 and 25'OH vitamin D levels in blood
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in homocysteine levels in blood
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in ghrelin, chinolinic acid and serotonin levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in fecal metabolomics (including production of short chain fatty acids verified by gas-chromatography)
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in highly sensitive C reactive protein levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in erythrocite sedimentation rate
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in fibrinogen blood levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in IL-6 blood levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in Tumor Necrosis Factor alfa blood levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
Secondary outcomes:
measure: Changes in body mass index
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in systemic arterial systolic and diastolic blood pressure
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in height
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in weight
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in waist circumference
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Entity of reduction of triceps skinfold thickness
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in prevalence of aphtous stomatitis
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in chinolinic acid, serotonin, ghrelin levels in blood
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in complete cell blood count
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in total cholesterol levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in HDL cholesterol levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in LDL cholesterol levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in triglycerides levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in Apolipoprotein A1 levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in Apolipoprotein B levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in fasting glucose levels
timeFrame: T0 T1 (+4 months)
measure: Changes in fasting insulin levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in auto-antibody anti endomisium titer
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in auto-antibody anti-transglutaminase titer
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Changes in fecal calprotectin levels
timeFrame: Time point 0: day 0 Time point 1: after 4 months
measure: Prevalence of wildtype allele of MTHFR gene by gene sequencing
timeFrame: Time point 0: day 0 (at the enrollement)
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Ospedale San Paolo
Study officials:
References: