Celiac Disease and Vitamin Status: Evaluation of the Effect of Supplementation With a Probiotic (VIVOMIXX®) in a Cohoort of Celiac Patients
- Conditions
- Celiac Disease
- Interventions
- Drug: Probiotic VivomixxBehavioral: Gluten free dietOther: Placebo
- Registration Number
- NCT04160767
- Lead Sponsor
- University of Milan
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 90
- Celiac disease (diagnosis made according to European Society for Paediatric Gastroenterology Hepatology and Nutrition)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Probiotic Gluten free diet - Placebo Gluten free diet - Probiotic Probiotic Vivomixx - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Changes in fibrinogen blood 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 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 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 Changes in highly sensitive C reactive protein levels Time point 0: day 0 Time point 1: after 4 months
- Secondary Outcome Measures
Name Time Method Changes in prevalence of aphtous stomatitis 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) Changes in height 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 body mass index 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 Changes in complete cell blood count 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 chinolinic acid, serotonin, ghrelin levels in blood 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 weight 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 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
Trial Locations
- Locations (1)
Ospedale San Paolo
🇮🇹Milan, Italy