evaluation of the effect of l. casei dg® on vitamin d absorption in patients under vitamin d supplementation.

Conditions: Vitamin D Deficiency

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

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.

Keywords: 25-hydroxyvitamin d- 25(oh) d enterolactis food supplement lactobacillus paracasei cncm i-1572 probiotic