| CTRI Number |
CTRI/2017/12/010785 [Registered on: 06/12/2017] Trial Registered Prospectively |
| Last Modified On: |
18/11/2022 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Effect of Vitamin D3 on Functions of Kidney and Blood Vessels in Vitamin D Deficient Patients with Type 2 Diabetes Mellitus |
|
Scientific Title of Study
|
A Randomized Double-Blind Placebo-Controlled Trial Evaluating the Efficacy of Oral Vitamin D3 in Improving Renal and Vascular Functions in Vitamin D Deficient Patients with Type 2 Diabetes Mellitus |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Saibal Das |
| Designation |
Senior Resident |
| Affiliation |
​Jawaharlal Institute of Postgraduate Medical Education and Research |
| Address |
​Department of Clinical Pharmacology ​Jawaharlal Institute of Postgraduate Medical Education and Research Pondicherry PONDICHERRY 605006 India |
| Phone |
9433429401 |
| Fax |
|
| Email |
saibaldas123@gmail.com |
|
Details of Contact Person Scientific Query
|
| Name |
Dr Sandhiya Selvarajan |
| Designation |
Associate Professor |
| Affiliation |
Jawaharlal Institute of Postgraduate Medical Education and Research |
| Address |
​Department of Clinical Pharmacology ​Jawaharlal Institute of Postgraduate Medical Education and Research Pondicherry PONDICHERRY 605006 India |
| Phone |
9443492922 |
| Fax |
|
| Email |
sandhiyaselvarajan@gmail.com |
|
Details of Contact Person Public Query
|
| Name |
Dr Sadish Kumar Kamalanathan |
| Designation |
Additional Professor and Head |
| Affiliation |
Jawaharlal Institute of Postgraduate Medical Education and Research |
| Address |
​Department of Endocrinology ​Jawaharlal Institute of Postgraduate Medical Education and Research Pondicherry PONDICHERRY 605006 India |
| Phone |
9629528518 |
| Fax |
|
| Email |
sadishkk@gmail.com |
|
|
Source of Monetary or Material Support
|
| Intramural fund, Jawaharlal Institute of Postgraduate Medical Education and Research, ​​​​Puducherry |
|
|
Primary Sponsor
|
| Name |
Intramural fund |
| Address |
​Jawaharlal Institute of Postgraduate Medical Education and Research,
​​​​Puducherry |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Saibal Das |
​​​​Jawaharlal Institute of Postgraduate Medical Education and Research |
Senior Resident Room, Department of Clinical Pharmacology,
​​​​Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Puducherry: 605 006 Pondicherry PONDICHERRY |
9433429401
saibaldas123@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee (Human Studies), ​Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Vitamin D deficient patients with type 2 diabetes mellitus, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Group 1 |
Oral vitamin D3 (cholecalciferol) 60,000 IU weekly for 8 weeks |
| Comparator Agent |
Group 2 |
Oral similar looking placebo weekly for 8 weeks |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Patients of either gender aged between 18 and 65 years with type 2 diabetes mellitus with or without hypertension and has stable clinical profile and receiving treatment ≥ 3 months.
2. Serum 25-hydroxy vitamin D level < 20 ng/ml.
3. Estimated GFR (eGFR) between 30 and 60 mL/min/1.73m2. |
|
| ExclusionCriteria |
| Details |
1. Patient on vitamin D-based therapy within 6 months prior to screening.
2. Patients with symptomatic vitamin D deficiency
3. Patient with a history of allergy or sensitivity to vitamin D or its analogues.
4. Patient with blood pressure ≥ 160/100 mm Hg or < 80/60 mm Hg.
5. Patient with uncontrolled diabetes: fasting blood glucose > 200 mg/dL or post prandial blood glucose > 350 mg/dL or HBA1C > 10.5%
6. Patients with coexisting diseases, such as, chronic gastrointestinal disease, myocardial infarction, cerebrovascular accident, congestive heart failure, cardiomyopathies, peripheral vascular diseases, malignancies and renal stones.
7. Patient with history of any drug or alcohol abuse ≤ 6 months prior to the screening.
8. Patient has received any investigational drug ≤ 3 months prior to this study.
9. Patient on any drugs modulating calcium metabolism and homeostasis. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
1. Urinary albumin creatinine ratio
2. Carotid-femoral pulse wave velocity |
a) At baseline
b) At end of treatment (end of 8 weeks)
c) At end of follow-up (end of 24 weeks) |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. Estimated glomerular filtration rate (eGFR)
2. Inflammatory markers (hs-CRP, TNF-alpha, IL-6 and IL-10)
3. Parameters of vascular functions (blood pressure, brachial-ankle pulse wave velocity, arterial stiffness index, aortic pressures and augmentation index)
4. Patient-related adverse drug reactions |
a) At baseline
b) At end of treatment (end of 8 weeks)
c) At end of follow-up (end of 24 weeks) |
|
|
Target Sample Size
|
Total Sample Size="100" Sample Size from India="100"
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="100" |
|
Phase of Trial
|
Phase 4 |
|
Date of First Enrollment (India)
|
01/05/2018 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="2" Months="0" Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
None yet. |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
The prevalence of chronic kidney disease (CKD) estimated to be 8–16% globally and is showing a progressively increasing trend. This is substantially contributed by growing global population of patients with diabetes. Diabetic patients develop diabetic nephropathy (DN), which along with co-existing hypertension leads to progressive impairment in renal function. Albuminuria in diabetes is associated with linear decline in glomerular filtration rate, progression to end stage renal disease and cardiovascular mortality. Drugs reducing the extent of proteinuria are considered to be a promising approach for preventing the progression of DN. Diabetic patients with early CKD tend to have multiple cardiovascular comorbidities mainly due to inflammation and endothelial dysfunction. Microalbuminuria, manifested in DN is considered to be an atherosclerotic risk factor and has been implicated as an independent risk factor for cardiovascular and cerebrovascular disease and premature cardiovascular mortality for patients with diabetes. Patients with CKD are profoundly deficient in both serum 25(OH)D3 and 1,25(OH)2D3, with 50-80% of patients at the initiation of chronic hemodialysis showing serum 25-hydroxy vitamin D levels below the lower limits of normal. They often have co-existing hypertension, which leads to increased mortality, cardiovascular complications and renal disease progression. Observational studies have demonstrated that CKD patients treated with vitamin D analogues have a significant better renal outcome as compared to untreated patients. It has been demonstrated that vitamin D deficiency has a negative effect on albuminuria in DN while vitamin D supplementation has a beneficial effect on the risk factors of diabetes, such as, hyperlipidemia, hypertension and hyperglycemia. A recent Indian study has shown that diabetics with vitamin D deficiency may be also at higher risk of vascular complications including coronary artery disease. A recent study from our centre has exhibited that oral vitamin D3 supplementation of 60,000 IU per week for 8 weeks significantly improves vascular functions and reduces oxidative stress in type 2 diabetic patients with vitamin D deficiency. Available evidence from low-to-moderate quality observational studies and fewer randomized control trials (RCTs) suggests that vitamin D supplementation improves biochemical endpoints, renal and vascular functions in diabetic kidney disease. However, whether such improvements in the early or intermediate stage of CKD in diabetes can translate into clinically significant outcomes, such as, slowing the progression of CKD or improving vascular functions on a long term basis is yet to be determined. If this study comes with a positive outcome, vitamin D supplementation might be warranted to prevent progression of renal dysfunction and also to improve vascular functions in patients with type 2 diabetes mellitus. |