Celiac DiseasePhase 4VIVOMIXXNCT04160767
Celiac Disease and Vitamin Status: Evaluation of the Effect of Supplementation With a Probiotic (VIVOMIXX®) in a Cohoort of Celiac Patients
A Phase 4 study testing Probiotic Vivomixx and Gluten free diet in people with Celiac Disease, run by University of Milan at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages Up to 14 years, men only
- Conditions the study is for
- Celiac Disease
- What is being tested?
- Probiotic Vivomixx and Gluten free diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteItaly
- Study dates
- 30 Jan 2019to Jul 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 14 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Celiac disease (diagnosis made according to European Society for Paediatric Gastroenterology Hepatology and Nutrition)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Ospedale San Paolo
Milan, 20142
Elvira Verduci, MD PhD Assistant Professor, +39 0281844508, elvira.verduci@unimi.it
About this study
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
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.
Read the 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.
- Conditions
- Celiac Disease
- Being tested
- Probiotic Vivomixx, Gluten free diet, Placebo
- Keywords
- Celiac disease, Gut microbiota
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic VivomixxDrug
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.
Gluten free dietBehavioural
Gluten free diet will be encouraged in both arms
PlaceboOther
Placebo with same taste than VIVOMIXX, containing maltose and silicon dioxide once a day for 4 months.
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Active comparator | Not described Receives: Drug: Probiotic Vivomixx; Behavioral: Gluten free diet |
| Placebo | Placebo comparator | Not described Receives: Behavioral: Gluten free diet; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in vitamin B6, folic acid, vitamin B12 and 25'OH vitamin D levels in blood
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in homocysteine levels in blood
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in ghrelin, chinolinic acid and serotonin levels
Measured: 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)
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in highly sensitive C reactive protein levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in erythrocite sedimentation rate
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in fibrinogen blood levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in IL-6 blood levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in Tumor Necrosis Factor alfa blood levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Secondary outcomes (21)
Changes in body mass index
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in systemic arterial systolic and diastolic blood pressure
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in height
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in weight
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in waist circumference
Measured: Time point 0: day 0 Time point 1: after 4 months
Entity of reduction of triceps skinfold thickness
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in prevalence of aphtous stomatitis
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in chinolinic acid, serotonin, ghrelin levels in blood
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in complete cell blood count
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in total cholesterol levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in HDL cholesterol levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in LDL cholesterol levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in triglycerides levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in Apolipoprotein A1 levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in Apolipoprotein B levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in fasting glucose levels
Measured: T0 T1 (+4 months)
Changes in fasting insulin levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in auto-antibody anti endomisium titer
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in auto-antibody anti-transglutaminase titer
Measured: Time point 0: day 0 Time point 1: after 4 months
Changes in fecal calprotectin levels
Measured: Time point 0: day 0 Time point 1: after 4 months
Prevalence of wildtype allele of MTHFR gene by gene sequencing
Measured: Time point 0: day 0 (at the enrollement)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2019
- Study start30 Jan 2019
- Primary completionJul 2021 (estimated)
- Study completionJul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Celiac DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elvira Verduci, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04160767
- Sponsor's protocol ID
- 2015/ST/135-3
- Acronym
- VIVOMIXX
- Status last verified
- Feb 2021
- First submitted
- 7 Nov 2019
- Last updated
- 10 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04160767
- Acronym / sponsor ID
- VIVOMIXX / 2015/ST/135-3
- Conditions
- Celiac Disease
- Keywords
- Celiac disease, Gut microbiota
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- 30 Jan 2019 (actual)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Jul 2021 (estimated)
- First posted
- 13 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Active comparator | Drug: Probiotic Vivomixx, Behavioral: Gluten free diet |
| Placebo | Placebo comparator | Behavioral: Gluten free diet, Other: Placebo |
Who may qualify
- Ages
- Up to 14 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Celiac disease (diagnosis made according to European Society for Paediatric Gastroenterology Hepatology and Nutrition)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic VivomixxVIVOMIXX 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. | Drug | Probiotic |
| Gluten free dietGluten free diet will be encouraged in both arms | Behavioural | Placebo, Probiotic |
| PlaceboPlacebo with same taste than VIVOMIXX, containing maltose and silicon dioxide once a day for 4 months. | Other | Placebo |
Primary outcome
Changes in vitamin B6, folic acid, vitamin B12 and 25'OH vitamin D levels in blood
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in homocysteine levels in blood
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in ghrelin, chinolinic acid and serotonin levels
Time frame: 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 frame: Time point 0: day 0 Time point 1: after 4 months
Changes in highly sensitive C reactive protein levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in erythrocite sedimentation rate
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in fibrinogen blood levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in IL-6 blood levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in Tumor Necrosis Factor alfa blood levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
21 secondary outcomes
Changes in body mass index
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in systemic arterial systolic and diastolic blood pressure
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in height
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in weight
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in waist circumference
Time frame: Time point 0: day 0 Time point 1: after 4 months
Entity of reduction of triceps skinfold thickness
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in prevalence of aphtous stomatitis
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in chinolinic acid, serotonin, ghrelin levels in blood
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in complete cell blood count
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in total cholesterol levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in HDL cholesterol levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in LDL cholesterol levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in triglycerides levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in Apolipoprotein A1 levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in Apolipoprotein B levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in fasting glucose levels
Time frame: T0 T1 (+4 months)
Changes in fasting insulin levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in auto-antibody anti endomisium titer
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in auto-antibody anti-transglutaminase titer
Time frame: Time point 0: day 0 Time point 1: after 4 months
Changes in fecal calprotectin levels
Time frame: Time point 0: day 0 Time point 1: after 4 months
Prevalence of wildtype allele of MTHFR gene by gene sequencing
Time frame: Time point 0: day 0 (at the enrollement)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2021.
- Individual participant dataSharing planned: No
Related trials for Celiac Disease
Active, not recruitingEarly Phase 1
VTP-1000 in Adults With Celiac Disease
Celiac Disease
RecruitingObservational study
Impact of Mediterranean Diet and Processed Food Consumption on Gastrointestinal Symptoms in Coeliac Patients on a Gluten-Free Diet
Celiac Disease, Gluten-free Diet
Recruiting
GF-NOURISH (Gluten Free Nutrition Optimization Through Ultra-processed Food Reduction and Improved Strategies for Health)
Celiac Disease in Children, Nutrition Disorder, Child
RecruitingObservational study
Celiac Disease Genomic Environmental Microbiome and Metabolomic Study
Celiac Disease
RecruitingObservational study
Pathogenic Study of Adult Immune Enteropathies
Celiac Disease, Autoimmune Enteropathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Probiotic Vivomixx and Gluten free diet in people with Celiac Disease, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in vitamin B6, folic acid, vitamin B12 and 25'OH vitamin D levels in blood (time frame: Time point 0: day 0 Time point 1: after 4 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2021.