Effects Of Vitamin D On Bone, Muscle, And Adipose Tissue In Obese Subjects
NCT Number: NCT06508242
Acronym: DON3
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Musculoskeletal Diseases|Inflammation|Sarcopenic Obesity
Interventions: DRUG: Cholecalciferol|OTHER: Placebo
Sponsor: Fondazione Policlinico Universitario Campus Bio-Medico
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 80
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: SUPPORTIVE_CARE
Start Date: 2023-04-28
Completion Date: 2025-12-31
Locations: Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Roma, RM, 00128, Italy

Summary:
Obesity has emerged as a risk factor in the onset of bone, muscle and adipose tissue impairments that are further aggravated by vitamin D deficiency. A link of an active bone-muscle-adipose axis is represented by Wnt pathway. This study will test the hypothesis that vitamin D improves bone, muscle, and adipose tissue health through a positive modulation of Wnt pathway. It will be carried out a double-blind, placebo-controlled study of cholecalciferol supplementation in vitamin D-deficient obese adults. Specific aims will be: 1) to test the direct effect of vitamin D on Wnt signaling in bone, muscle, and adipose tissue; 2) to evaluate muscle mass and strength; 3) to assess changes in vitamin D status across different administration strategy (weekly, fortnightly, monthly).

This study will provide not only insight of new mechanisms involved in the pathophysiology of obesity-related musculoskeletal impairments but also evidence for new treatment recommendations for vitamin D deficiency in obesity.

Primary Outcome Measures: WNT pathway regulation, Specifically, WNT10b, WNT5a, sFRP5, pGSK-3ß-Ser9 and total GSK-3ß expression will be evaluated and subsequently confirmed by RT-PCR and Western-blot analysis on adipose and muscle tissue. Serum sclerostin,DDK-1 and sFRP5 will be also evaluated by ELISA, from 6 to 30 months
Secondary Outcome Measures: Muscle strength and function, • Gene involved in myogenesis will be analyzed by RT-PCR (Relative Expression) and Western-blot (Relative Abundance)., from 0 to 32 months|Muscle strength and function, • RNAseq will be performed on muscle biopsies to address changes in the transcript profile and subsequent gene enrichment analysis related to vitamin D supplementation, from 0 to 32 months|Muscle strength and function, • Exosomal-miRNAs will be isolated from treated and untreated adipose tissue with Vitamin D, from 0 to 32 months|Muscle strength and function, Following tests will be performed:

• MRI and total body DXA to characterize muscle health status and muscle quality, from 0 to 32 months|Muscle strength and function, • Muscle quality will be assessed also by calculating the ratio of Lower extremity (LE) strength to LE lean body mass (by DXA, g/cm\^2), from 0 to 32 months|Muscle strength and function, • Handled dynamometer (to test muscle strength, Kg)., from 0 to 32 months|Muscle strength and function, • Physical performance evaluation by modified and gait-speed test (m/s)., from 0 to 32 months|Muscle strength and function, • Validated questionnaires for sarcopenia assessment such as SARC-F and MSRA (Units on a scale), from 0 to 32 months|Effects of inflammation and WNT pathway on adipose tissue, • Analysis of gene and protein expression of molecules related to Inflammation and the effects of WNT pathway on adipose tissue, from 0 to 32 months|Effects of inflammation and WNT pathway on adipose tissue, • RNA transcription will be performed as described above, as well as exosome analysis., from 0 to 32 months|Effects of inflammation and WNT pathway on bone tissue, • Analysis of gene expression of the genes related to WNT pathway, from 0 to 32 months|Effects of inflammation and WNT pathway on bone tissue, • An immunohistochemistry assay will be performed on the bone to analyze the number and localisation of Teff and Treg cells., from 0 to 32 months|Effects of inflammation and WNT pathway on bone tissue, • Synovial fluid: measurement of pro- and anti-inflammatory/metabolic molecules using the Luminex technology, from 0 to 32 months