Clinical trial NCT05394207: Evaluation Of The Effect Of L. Casei DG® On Vitamin D Absorption In Patients Under Vitamin D Supplementation.
Official title: Evaluation Of The Effect Of L. Casei DG® (L. Paracasei CNCM I1572) On Vitamin D Absorption In Patients Under Vitamin D Supplementation. Double-Blind, Exploratory, Randomized, Controlled Clinical Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Vitamin D Deficiency
Keywords: 25-hydroxyvitamin D- 25(OH) D
ENTEROLACTIS
food supplement
Lactobacillus paracasei CNCM I-1572
probiotic
Lead sponsor: SOFAR S.p.A.
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-Blind, Exploratory, Randomized, Controlled
Primary purpose: TREATMENT

Brief summary: Vitamin D deficiency is one of the most underdiagnosed and undertreated medical condition worldwide . The microbiome and vitamin D deeply influence each other and the immune system in many different ways. It is evident that the immune system and the microbiome are interconnected, and that vitamin D is a critical intermediary player in this dynamic .

Probiotics were shown to increase vitamin D intestinal absorption and increase vitamin D receptor protein expression and transcriptional activity . Likewise, vitamin D receptor status seems to be crucial in regulating the mechanisms of action of probiotics and modulating their anti-inflammatory, immunomodulatory and anti-infective benefits, suggesting a two-sided pathway . The objective of this study is to assess the different absorption of Vitamin D (Vit. D) between patients treated with Vit. D supplementation combined to a probiotic containing L. casei DG® and patients treated with Vitamin D supplementation and placebo

Detailed description: The present study is a monocentric, exploratory, randomized, double-blind, controlled study to evaluate the effects of daily intake of L. Casei DG® (L. Paracasei CNCM I1572) on vitamin D absorption in adult patients with Vitamin D (Vit. D) deficiency, defined as a blood level of 25(OH) D ≤ 20 ng/ml.

The investigational product is ENTEROLACTIS®, a food supplement resulting from SOFAR research (listed in the Food Supplement Registry of the United Arab Emirates Ministry of Health \& Prevention with the code #12235-13911-2) available as drinkable vials of 10 ml, containing 8 billion of live cells of L. casei DG The comparator product is an identical drinkable vial of placebo. Vit. D will be provided by the sponsor as oral drops of 10. 000 U.I./mL 16 drops of Vit. D must be dissolved in the Investigational Product/placebo vial and then this has to be reconstituted and drunk immediately.

The patients will be involved in 10 on site visits: V-1 (Screening)- within 7 days before baseline visit, V0 (Baseline) at the start of therapy, V1- 1 week after the start of therapy, 6 visits (V2-V7) every two weeks and V8- follow up visit, 4 weeks after the end of treatment (EOT-V7).

Investigational Product/comparator treatment will start at V0 and will end at V7, for a duration of 12 weeks. After the End of Treatment visit (EOT-V7), patients will enter in a 4 weeks Follow Up (FU) period, for a total duration of the study of 16 weeks (12 weeks of treatment + 4 weeks of FUP). If a patient reaches normal levels of Vitamin D before EOT visit, study treatment will be interrupted, and patient will enter the FU period.

Eligibility criteria: Inclusion Criteria:

1. Male and female adults aged ≥ 18 and ≤ 60 years;
2. Middle East Area residency;
3. Serum levels of Vit. D≤ 20 ng/ml at screening, for which a course of Vitamin D at a dose of 4.000 U.I. daily has been prescribed as per clinical practice;
4. Body Mass Index (BMI) between 18,50 and 29,99;
5. Acceptance of the study by the patient and written informed consent to participate in the study provided.

Exclusion Criteria:

1. Serum level of Vit. D \> 20ng/ml;
2. Documented malabsorption of Vit. D and/or other oligoelements and vitamins;
3. BMI ≤ 18.5 and ≥29,99;
4. Hypersensitivity to cholecalciferol or to any of the excipients of the prescribed drug;
5. Contraindications to Vit. D supplementation (e.g. hypercalcemia, hypercalciuria, renal failure);
6. Vit. D therapy or prophylaxis within 30 days before the enrolment in this study;
7. History of administration of systemic antibiotics or antibiotics at bowel action (es: rifaximin) within 30 days before the enrolment in this study;
8. History of administration of probiotics, prebiotics, (including probiotic/prebiotic enriched foods) within 30 days before the enrolment in this study;
9. Present treatment with Proton Pump Inhibitors (PPIs) and aluminium-containing antacids;
10. Present treatment with drugs interfering on the absorption of Vit. D, as barbiturates, antiepileptics (i.e. phenobarbital, phenytoin, carbamazepine), corticosteroids, antimycotics (i.e. ketoconazole, fluconazole), anti-retroviral agents, cholestyramine, colestipol, orlistat;
11. Patients with certain or suspected diagnosis of chronic inflammatory bowel diseases, cystic fibrosis or mucoviscidosis;
12. Patients with hepatic impairment (Alanine transaminase (ALT) or Aspartate aminotransferase (AST)\>3 times the upper limit of normal);
13. Patients with nephrolithiasis or nephrocalcinosis;
14. Infective gastro-intestinal syndromes in active phase or gastro-intestinal infectious residue which can alter the bowel absorption on the judgement of the investigator;
15. Episodes of viral or bacterial enteritis within 2 months before the enrolment in the study;
16. History or presence of gastric and/or duodenal ulcers;
17. Psychiatric syndromes and/or psychological disturbances;
18. Any severe pathology which could interfere with the study treatment;
19. Presence of any relevant severe condition or clinically relevant abnormal laboratory parameters that in the opinion of the investigator may interfere with the participation to the study;
20. Poor reliability or presence of conditions leading to a poor compliance/adherence to the protocol by the patient;
21. Active malignancy of any type, or history of a malignancy (patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before study enrolment are also acceptable);
22. Pregnancy and/or breastfeeding\*;
23. Existence of mental illness or any mental condition potentially interfering with appropriate compliance with protocol procedures;
24. Patients without self-judgement ability;
25. Participation in another investigational study or treatment with any investigational drug within the previous 30 days;
26. Recent history or suspicion of alcohol abuse or drug addiction;
27. Patients not compliant with the procedures of the protocol.

Primary outcomes:
measure: Serum levels of vitamin D (25-hydroxyvitamin D- 25(OH) D) measured in ng/mL
timeFrame: week 12
Secondary outcomes:
measure: Time to reach normal serum levels of Vit. D.
timeFrame: week 12
measure: Presence of L. casei DG® strain in faeces
timeFrame: week 12
measure: Modification from baseline of faecal microbiota in terms of indices of microbial α diversity
timeFrame: week 12
measure: Modification from baseline of faecal microbiota in terms of indices of microbial β diversity
timeFrame: week 12
measure: Modification from baseline of faecal microbiota in terms of indices of microbial relative taxonomic abundance
timeFrame: week 12
measure: Modification from baseline of faecal short-chain fatty acid (SCFAs);
timeFrame: week 12
measure: Modification of serum levels of Interleukin 6 (IL-6), Interleukin 8 (IL-8), Interleukin 10 (IL-10)
timeFrame: week 12
measure: Modification of serum levels of C reactive protein (CRP)
timeFrame: week 12
measure: Modification of serum levels of zonulin
timeFrame: week 12
measure: Modification of serum levels of total cholesterol, LDL, HDL and triglycerides
timeFrame: week 12
measure: Evaluate the overall patient satisfaction with treatment
timeFrame: week 12
Other outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: week 16
Locations:
city: Dubai
country: United Arab Emirates
facility: Rashid Hospital
Study officials:
References: