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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  
Name  Address 
NIL  NIL 
 
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  
Status 
Not Applicable 
 
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. 

 
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