Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
80
Countries
1
Sites
1
obese elderly people with vitamin D deficiency
To evaluate the effect of cholecalciferol supplementation on inflammation in obese patients with vitamin D deficiency
Key facts
- Sponsor
- Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
- Participant type
- Patients
- Age range
- 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
- Trial duration
- 31 Jan 2025 → ongoing
- Decision date (initial)
- 2025-01-31
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Italian Ministry of Health PNRR-MCNT2-2023-12378489
External identifiers
- EU CT number
- 2025-520869-52-00
- EudraCT number
- 2019-003907-37
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To evaluate the effect of cholecalciferol supplementation on inflammation in obese patients with vitamin D deficiency
Secondary objectives 4
- Evaluate the inflammatory processes of muscle and adipose tissue following supplementation with cholecalciferol
- To evaluate the effects of cholecalciferol supplementation on the modulation of the WNT pathway in bone, muscle and adipose tissue in obese subjects
- Evaluate the safety of cholecalciferol supplementation
- For exploratory purposes, it will also be evaluated whether cholecalciferol supplementation is able to reduce bone marrow fat.
Conditions and MedDRA coding
obese elderly people with vitamin D deficiency
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10029885 | Obesity unspecified | 10027433 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Single-center, non-profit, phase IV, randomized, double-blind study Both groups will take treatment until surgery scheduled 12 weeks from baseline
|
Randomised Controlled | Double | [{"id":174199,"code":2,"name":"Investigator"},{"id":174198,"code":1,"name":"Subject"}] | Group A: 50,000 IU of cholecalciferol Group B: Placebo |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Obtaining written informed consent
- Willingness to adhere to the procedures foreseen by the study, as reported in the informed consent
- 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
- BMI >= 30 kg/m2
- 25(OH)D levels < 20 ng/ml
Exclusion criteria 13
- eGFR < 40 ml/min./1.72 m2 estimated via EPI formula
- Hypercalcemia (>10.5 mg/dL)
- Nephrolithiasis known by medical history
- 4. Conditions that can alter the metabolism of calcium and vitamin D (primary hyperparathyroidism, hyperthyroidism, chronic renal failure, liver failure, hypercortisolism, malabsorption, HIV)
- 5. Use 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)
- Immobilized patients
- Alcohol and/or tobacco abuse
- Clinical history of bone metastases or neoplastic bone diseases
- Paget's disease
- Osteoporosis (femoral or vertebral t-score > -2.5)
- Pathologies at the site of surgery
- Participation in interventional clinical trials in the previous 3 months
- Hypersensitivity to cholecalciferol or to any of the excipients
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Serum: Changes in the pro-inflammatory cytokine TNF-alpha will be evaluated via ELISA assay.
Secondary endpoints 9
- 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
- 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
- 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.
- Synovial fluid: Measurement of pro- and anti-inflammatory/metabolic molecules using the Luminex assay as previously described.
- 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.
- 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.
- 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.
- 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.
- Intramedullary fat: The quantification of intramedullary fat will take place via magnetic resonance spectroscopic (MRS)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP102627814 · ATC
- Active substance
- Colecalciferol
- Substance synonyms
- CHOLECALCIFEROL, VITAMIN D3, COLECALCIPHEROL
- Route of administration
- ORAL USE
- Max daily dose
- 7000 IU international unit(s)
- Max total dose
- 50000 IU international unit(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- A11CC05 — COLECALCIFEROL
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 2
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
- Sponsor organisation
- Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
- Address
- Via Alvaro Del Portillo N 200
- City
- Rome
- Postcode
- 00128
- Country
- Italy
Scientific contact point
- Organisation
- Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
- Contact name
- Prof. Nicola Napoli
Public contact point
- Organisation
- Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
- Contact name
- Prof. Nicola Napoli
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 80 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2025-01-31 | 2025-02-28 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 11 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2025-520869-52-00 _english_clean_FP | 5 |
| Protocol (for publication) | D1_Protocol 2025-520869-52-00_ita_CLEAN_NfP | 6 |
| Protocol (for publication) | D1_Protocol_2025-520869-52-00_FP | 6 |
| Recruitment arrangements (for publication) | Recruitment procedures | 1.0 |
| Subject information and informed consent form (for publication) | L1_ICF Privacy_FP | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_FP | 5.0 |
| Subject information and informed consent form (for publication) | L2_Other Subject Information_GPL_FP | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Cholecalciferol | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis IT_2025-520869-52-00 | 4.0 |
| Synopsis of the protocol (for publication) | D4_Patient facing documents | 1 |
| Synopsis of the protocol (for publication) | Summary of Changes SM-1 RFI-002 | 2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-30 | Italy | Acceptable with conditions 2025-01-30
|
2025-01-31 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-12-11 | Italy | Acceptable 2026-03-26
|
2026-03-27 |