Vitamin D Supplementation on Surrogate Markers of Atherosclerosis

Study Overview
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Brief Summary
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For this study, our sample population is individuals with prediabetes, who are at an increased risk for atherosclerosis. In this proposed randomized placebo-controlled prospective trial, we would be enrolling 120 subjects with prediabetes having vitamin D deficiency. These subjects will be randomized into two groups; lifestyle modification counselling along with intervention with either vitamin D supplementation or placebo. Clinical and dietary profiles including sunlight exposure, anthropometry, glycemic and lipid profiles, fasting insulin, adiponectin, body composition (DEXA), skinfolds (4 sites), surrogate markers of atherosclerosis/inflammation (TNF-alpha, hs-CRP, Matrix Metalloproteinase-9, flow-mediated dilatation of brachial artery, pulse wave velocity, and carotid intima-mediated thickness) will be measured at week 0 and week.

Detailed Description
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Prediabetes is a substantial problem in India not only because it itself can be associated with morbidities such as coronary artery disease but also because it is a point of important for prevention of diabetes. It is not clear if vitamin D supplementation in Indian population associated with heightened tendency for prediabetes, metabolic syndrome, atherosclerosis and dys-metabolic state etc. could, besides lifestyle factors, be related to vitamin D deficiency, or interaction between the two. This study is based on the assumption that the supplementation of vitamin D may decrease Atherosclerosis in individuals with prediabetes. Supplementation of vitamin D is of major significance in terms of economic and health benefits to the individual and to the country. In addition, such simple and low-cost measures would help maintain a normal metabolic system. The proposed study would also lead to a community-based model of education regarding metabolic and cardiovascular disease. This study will help to develop slandered protocol for the prevention and treatment of non-communicable diseases (NCDs). In India, the prevalence of coronary heart disease (7%-13% in urban and 2%-7% in rural populations), as well as diabetes, is high. Positive results from this study may benefit a large number of individuals at risk for cardiovascular disease. In addition, If vitamin D supplementation leads to decreased atherosclerosis as indicated by surrogate markers of atherosclerosis, it may be a cost-effective and novel way to reduce or prevent atherosclerosis in the Indian population, which is at high risk for the development of atherosclerosis.

Official Title
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Effect of Vitamin D Supplementation on Surrogate Markers of Atherosclerosis in North Indian Individuals With Pre-diabetes and Low Vitamin D Levels: a Randomised Controlled Trial.

Conditions
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Atherosclerosis

Intervention / Treatment
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* Other: Vitamin D supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-diabetes: fasting blood glucose ≥100mg/dl and <125.99mg/dl, 2-h plasma glucose ≥140mg/dl and <200mg/dl (after ingestion of 75 g anhydrous oral glucose). Baseline level of 25 hydroxy vitamin D <30ng/dl and aged 20-60 years. Exclusion Criteria: Received Vitamin D and/or calcium supplementation in the previous six months, on any medication within the last one month which could potentially influence insulin secretion, insulin sensitivity, vitamin D or calcium metabolism (eg metformin, thiazolidione, steroids etc) and on any medication that activate steroid and xenobiotic receptor and drugs used in transplantation (e.g. steriods, calcitonin etc.) Severe end-organ damage, any malignancy, nephrotic syndrome, malabsorption etc, Known case of HIV infection, hyperparathyroidism, granulomatous disorders (e.g. sarcoidosis)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: A randomized open labelled placebo-controlled trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D supplementation<br>Appropriate diet and physical activity counselling Supplementation with Vitamin D and oral Calcium- Doses of cholecalciferol (commercial name, Calcirol) 60,000 international units (sachets, dissolved in half glass milk) once per week for eight weeks to intervention group and placebo (Lactose granules) to the placebo group according to the random numbers generated by the computer. After every 24 weeks blood 25 (OH) D levels will be assessed. If the subjects are found to be still deficient then supplementation of cholecalciferol 60,000 IU per week for eight weeks will be repeated. If the 25 (OH) D levels are normal, then cholecalciferol supplementation in doses of 200 international units per day will be given as a maintenance dose. | Other: Vitamin D supplementation<br>* Appropriate diet and physical activity counselling to both groups. Supplementation with Vitamin D and oral Calcium-Doses of cholecalciferol (commercial name, Calcirol) 60,000 IU (sachets, dissolved in half glass milk) once per week for eight weeks for the intervention group and placebo (Lactose granules) to the placebo group according to the random numbers generated by the computer. After every 24 weeks blood 25 (OH) D levels will be assessed. If the subjects are found to be still deficient then supplementation of cholecalciferol 60,000 IU per week for eight weeks will be repeated.If the 25 (OH) D levels are normal, then cholecalciferol supplementation in doses of 200 IU per day will be given as a maintenance dose. Equal doses of calcium carbonate (1gm per day, commercial name Calcal) will be given to both the groups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of vitamin D supplementation on structural of atherosclerosis | Carotid intima media thickness (CIMT) will be measured using a high resolution B-mode ultrasound machine equipped with an 11-MHz frequency linear probe, the procedure will be done by the same radiologist on the same ultrasound machine. All subjects (patients and control) will be examined in supine position, neck extended and chin facing the contralateral side, both common carotid arteries will be examined in both longitudinal and transverse scans, three consecutive measurements of intima media thickness will be taken from the far wall of both common carotid arteries, 1-2 cm proximal to the carotid bulb over the common carotid artery and in the proximal most portion of the internal carotid artery near its origin and the average of these 6 measurements from both sides will taken for final statistical analysis. | 2 .5 Years | 
| Effects of vitamin D supplementation on physiology of atherosclerosis | Brachial artery ultrasound study will be performed in a quiet, dark, temperature-controlled room, all the participants will be in supine position, resting for 10 min, and the measurements of brachial artery will be taken in longitudinal scan in the arm 5-10 cm above the antecubital fossa without permanent vascular access. The luminal diameter of the artery will be measured between the proximal and distal intima. | 2.5 Years | 
| Effects of vitamin D supplementation on biochemical profile of atherosclerosis | Biochemical: TNF-alpha, hs-CRP, Matrix Metalloproteinase-9. | 2.5 Years | 
| Effects of vitamin D supplementation on physiology of atherosclerosis | Pulse wave analysis: Using a Mobil-O-Graph (I.E.M., Stolberg, Germany), we will perform pulse wave analyses. The individuals will be performed during the time of pulse wave analysis four BP measurements. The determination of heart rate, peripheral and central pulse pressure, and arterial stiffness of Mobil-O-Graph PWV, also called oPWV, followed all Expert Consensus Document's recommendations on the measurement of Aortic Stiffness 2012. | 2.5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Prediabetes, Asian Indians