Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin D intervention group | Active Comparator | 50.000 IU of oral cholecalciferol/week |
|
| Placebo group | Placebo Comparator | Placebo treatment/week |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cholecalciferol | Drug | cholecalciferol |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nicola Napoli, PhD | Contact | +3906225419151 | N.Napoli@policlinicocampus.it | |
| Flavia Tramontana, PhD | Contact | +3906225419152 | f.tramontana@unicampus.it |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fondazione Policlinico Universitario Campus Bio-Medico di Roma | Recruiting | Roma | RM | 00128 | Italy |
Not provided
| ID | Term |
|---|---|
| D009140 | Musculoskeletal Diseases |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
double-blind
| Placebo |
| Other |
placebo |
|
• 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 |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |