Effects Of Vitamin D On Bone, Muscle, And Adipose Tissue In Obese Subjects

Phase 4

Recruiting

• Conditions: Inflammation; Musculoskeletal Diseases; Sarcopenic Obesity
• Interventions: Drug: Cholecalciferol; Other: Placebo

• Registration Number: NCT06508242
• Lead Sponsor: Fondazione Policlinico Universitario Campus Bio-Medico

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-04-28
• Status Verified: 2024-03
• Study First Submitted: 2024-03-25
• Study First Submitted QC: 2024-07-17
• Last Update Submitted: 2024-07-17
• Study First Posted: 2024-07-18
• Last Update Posted: 2024-07-18
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Ambulatory willing and able to provide informed consent;
• post-menopausal women (55-75 y.o.) and age-matched men;
• BMI 30 >= kg/m2;
• serum 25OHD < 20 ng/ml
• hip replacement surgery due to osteoarthritis according to orthopedic clinical decision

Exclusion Criteria

• eGFR <40 ml/min/1.72 m2 by EPI formula (21);
• hypercalcemia (>10.5 mg/dL);
• osteoporosis (hip or vertebral t-score >-2.5);
• conditions affecting bone
• vitamin D and/or calcium metabolism (chronic liver disease, renal failure, malabsorption, hypercortisolism);
• medications altering bone metabolism (e.g. denosumab, bisphosphonates, teriparatide, glucocorticoids, aromatase inhibitors, estrogen);
• enrollment in an interventional clinical trial in the previous 3 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Vitamin D intervention group	Cholecalciferol	50.000 IU of oral cholecalciferol/week
Placebo group	Placebo	Placebo treatment/week

Primary Outcome Measures

Name	Time	Method
WNT pathway regulation	from 6 to 30 months	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

Secondary Outcome Measures

Name	Time	Method
Effects of inflammation and WNT pathway on adipose tissue	from 0 to 32 months	• RNA transcription will be performed as described above, as well as exosome analysis.
Effects of inflammation and WNT pathway on bone tissue	from 0 to 32 months	• Synovial fluid: measurement of pro- and anti-inflammatory/metabolic molecules using the Luminex technology
Muscle strength and function	from 0 to 32 months	• Validated questionnaires for sarcopenia assessment such as SARC-F and MSRA (Units on a scale)

Trial Locations

Locations (1)

Fondazione Policlinico Universitario Campus Bio-Medico di Roma; 🇮🇹 Roma, RM, Italy