COLECALCIFEROL for Obesity | Vitamin D deficiency

Inclusion criteria

• {"criterion_text":"- Obtaining written informed consent\n- Willingness to adhere to the procedures foreseen by the study, as reported in the informed consent\n- Post-menopausal women between the ages of 55 and 75 and men of the same age for whom hip or knee replacement surgery has been scheduled\n- BMI >= 30 kg/m2\n- 25(OH)D levels < 20 ng/ml"}

Exclusion criteria

• {"criterion_text":"- eGFR < 40 ml/min./1.72 m2 estimated via EPI formula\n- Osteoporosis (femoral or vertebral t-score > -2.5)\n- Pathologies at the site of surgery\n- Participation in interventional clinical trials in the previous 3 months\n- Hypersensitivity to cholecalciferol or to any of the excipients\n- Hypercalcemia (>10.5 mg/dL)\n- Nephrolithiasis known by medical history\n- 4.\tConditions that can alter the metabolism of calcium and vitamin D (primary hyperparathyroidism, hyperthyroidism, chronic renal failure, liver failure, hypercortisolism, malabsorption, HIV)\n- 5.\tUse of drugs that can alter bone metabolism (estrogens, raloxifene, tamoxifen, bisphosphonates, denosumab, teriparatide, GnRH analogues, use of at least 5 mg per day of glucocorticoids for ≥ 3 months, anabolic steroids, dilantin, antiretrovirals, radiation therapy)\n- Immobilized patients\n- Alcohol and/or tobacco abuse\n- Clinical history of bone metastases or neoplastic bone diseases\n- Paget's disease"}

Primary endpoints

• {"endpoint_text":"- Serum: Changes in the pro-inflammatory cytokine TNF-alpha will be evaluated via ELISA assay.","definition_or_measurement_approach":"Changes in TNF-alpha measured in serum using ELISA assay."}

Secondary endpoints

• {"endpoint_text":"- Muscle tissue: Nuclear magnetic resonance imaging of the ilio-psoas muscle (MRN). Using RT-PCR, the gene expression of inflammatory cytokines (IL-6; IL-8; IL-10; TNF-; MCP-1) and adiponectin, myogenic proteins (myogenin, myo-D, MHC-2, MYH1/2, mTORC1, STAT3 and myostatin) as well as the expression of WNT pathway genes such as: WNT10b, WNT5a, GSK-3beta and sFRP5","definition_or_measurement_approach":"MRI (MRN) for ilio-psoas muscle imaging; RT-PCR for gene expression of listed cytokines, myogenic proteins and WNT pathway genes."}
• {"endpoint_text":"- Adipose tissue: Gene and protein expression analysis of IL-6 cytokines; IL-8; IL-10; TNF-alpha; IGF-1, adiponectin, markers inherent to the WNT pathway such as WNT5a, WNT10b, sFRP5 and GSK-3beta and the differentiation factor PPAR-gamma via RT-PCR and Western-Blot, respectively. RNA transcription will be performed as previously described, as will analysis of exosomes. Adipocytes will be isolated and the supernatant collected for pro- and anti-inflammatory cytokine testing using Luminex technolog","definition_or_measurement_approach":"RT-PCR for gene expression, Western-Blot for protein expression, exosome analysis, adipocyte isolation and supernatant tested for cytokines using Luminex technology."}
• {"endpoint_text":"- Bone tissue: RT-PCR will be used to evaluate the expression of the following genes: WNT5a, WNT10b, GSK-3beta, SOST, DKK-1 RUNX2, IGF-1 and osteocalcin. An immunohistochemical analysis will be performed on the bone to analyze the number and location of Teff and Treg cells. Skeletal tissues will be fixed and decalcified to stain slides with specific monoclonal antibodies, such as anti-CD4 and anti-FOXP3, to identify Teff and Treg cells.","definition_or_measurement_approach":"RT-PCR for listed genes; immunohistochemistry on decalcified bone using monoclonal antibodies (e.g., anti-CD4, anti-FOXP3) to identify Teff and Treg cells."}
• {"endpoint_text":"- Synovial fluid: Measurement of pro- and anti-inflammatory/metabolic molecules using the Luminex assay as previously described.","definition_or_measurement_approach":"Luminex assay measurement of pro- and anti-inflammatory/metabolic molecules in synovial fluid."}
• {"endpoint_text":"- Serum: The following cytokines and adipokines will be evaluated by ELISA assays: IL-6; IL-8; IL-10 and adiponectin as well as bone turnover markers: CTX, P1NP, active and inactive osteocalcin, BSAP. The serum concentration of 25-hydroxy-vitamin D will be evaluated using radioimmunoassays. Biomarkers of the WNT pathway such as: serum sclerostin, DKK-1 and sFRP will be evaluated using ELISA assays.","definition_or_measurement_approach":"ELISA assays for listed cytokines/adipokines and WNT biomarkers; radioimmunoassay for 25-hydroxy-vitamin D; assays for bone turnover markers as listed."}
• {"endpoint_text":"- In order to monitor the safety of cholecalciferol supplementation, the patient's blood calcium level will also be measured at each time point of the study.","definition_or_measurement_approach":"Serial blood calcium (calcemia) measurements at each study time point to monitor safety."}
• {"endpoint_text":"- PBMCs: Thanks to the execution of venous sampling, it will be possible to extract PMBCs to evaluate the frequency and phenotype of T cells. They will be evaluated by multiparametric flow cytometry to study CD4+, CD8+, Treg and TR3-56 T cells. A combination of the following fluorochrome-conjugated monoclonal antibodies will be used: anti-CD45, -CD3, -CD4, -CD8, -CD56, -CD25, -FoxP3, -CD45RA, -CCR7, -PD-1, -CTLA4. Dead cells detected by a viability dye will be excluded.","definition_or_measurement_approach":"Multiparametric flow cytometry on PBMCs using listed fluorochrome-conjugated monoclonal antibodies to evaluate frequency and phenotype of T-cell subsets; viability dye to exclude dead cells."}
• {"endpoint_text":"- PBMCs will be used to separate the two main subsets of T lymphocytes such as CD4+ and CD8+ T cells using a magnetic bead kit. The isolated cells will be cultured and stimulated or not via the TCR receptor; Cell supernatant will be analyzed via Luminex as previously described to measure both pro- and anti-inflammatory cytokines.","definition_or_measurement_approach":"Magnetic bead separation of CD4+/CD8+ T cells, in vitro culture and stimulation via TCR, and analysis of cell supernatants by Luminex for cytokine measurement."}
• {"endpoint_text":"- Intramedullary fat: The quantification of intramedullary fat will take place via magnetic resonance spectroscopic (MRS)","definition_or_measurement_approach":"Magnetic resonance spectroscopy (MRS) to quantify intramedullary fat."}

Italy

Earliest CTIS Part Ii Submission Date

29-01-2025

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

422

Number Of Sites

1

Number Of Participants

80

Primary sponsor

Full Name

Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Italian Ministry of Health PNRR-MCNT2-2023-12378489","duties_or_roles":"Monetary support","organisation_type":""}