Inflammation, Musculoskeletal Diseases, Sarcopenic Obesity
Conditions
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.
Interventions
DRUGCholecalciferol
cholecalciferol
OTHERPlacebo
placebo
Sponsors
Fondazione Policlinico Universitario Campus Bio-Medico
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Muscle strength and function | from 0 to 32 months | • Gene involved in myogenesis will be analyzed by RT-PCR (Relative Expression) and Western-blot (Relative Abundance). |
| Effects of inflammation and WNT pathway on adipose tissue | from 0 to 32 months | • Analysis of gene and protein expression of molecules related to Inflammation and the effects of WNT pathway on adipose tissue |
| Effects of inflammation and WNT pathway on bone tissue | from 0 to 32 months | • Analysis of gene expression of the genes related to WNT pathway |
Countries
Italy
Contacts
Primary ContactNicola Napoli, PhD
Backup ContactFlavia Tramontana, PhD
Outcome results
None listed