D Vitamin Intervention in VA

Study Overview
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Brief Summary
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This study will supplement African American male (AAM) veterans at risk for diabetes and newly diagnosed T2DM with vitamin D (low or higher dose) and evaluate whether vitamin D helps to improve early markers of diabetes. The study will be done at Veteran Administration Medical Center in Chicago.

Detailed Description
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The goal of this randomized clinical trial (RCT) is to determine vitamin D efficacy and safety for improving early markers of T2DM in African American male (AAM) veterans at risk for T2DM (n=205, duration 12 months). The primary outcome will be change in oral glucose insulin sensitivity (OGIS). The secondary outcomes will include various parameters of glucose metabolism and other biomarkers. Analysis based on primary and secondary goal as well as predetermined levels of A1C, OGTT and 25OHD at the end of the study.

Official Title
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Vitamin D Deficiency and Treatment in Male Veterans at Risk for Diabetes

Conditions
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Impaired Fasting Glucose, Impaired Glucose Tolerance, Vitamin D Insufficiency

Intervention / Treatment
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* Drug: Placebo
* Drug: 50K vitamin D2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veterans at Jesse Brown VA Medical Center (JBVAMC) only Male African American race Age 35-85 years BMI 28-39.9 kg/m2 Stable weight (+/- 10%) for at least 3 months prior to study entry FPG 95 - 125 mg/dl A1C 5.7 - 6.4% Circulating 25OHD 5.0 - 29.9 ng/ml Subjects who take ergocalciferol are allowed in the study after a washout period 1 3 month. Subjects who take vitamin D supplements other than ergocalciferol are allowed in the study as long as total dose is no more than 600 IU/day (including MVI and calcium plus D supplements). Non-diabetic subjects who are diagnosed with T2DM during screening (A1C 6.5-7%) or after randomization are allowed to continue if they follow lifestyle intervention and do not need to take anti-diabetic medications. Exclusion Criteria: Subjects with T2DM Weight gain or loss of more than 10% within 3 months prior to the study entry History of kidney stones, hyperparathyroidism, sarcoidosis or hypercalcemia A1C >7%. Very low 25OHD levels (<5 ng/ml) and/or the presence of a physical consequence of very low vitamin D levels (hypocalcemia, hypophosphatemia, proximal muscle weakness) Chronic kidney disease (CKD) stage 4 and 5 Problems that in the judgment of PI may be associated with the risk to the subject or non-compliance Subjects who take vitamin D supplements and not willing to go through washout period for ergocalciferol or to take no more than 600 IU/day of total vitamin D supplements History, clinical manifestations or medications of significant metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, psychiatric/ psychological disorders, or social circumstances which in the opinion of the investigator would be expected to interfere with the study or increase risk to the subject Non-diabetic subjects who are diagnosed with T2DM after randomization and need to take anti-diabetic medications are brought for the final visit

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1<br>Placebo: One capsule weekly | Drug: Placebo<br>* Supplement of vitamin D 400 units provided to all subjects, in addition Arm 1 will get placebo and Arm 2 will get D2 50K<br>|
| Experimental: Arm 2<br>50K vitamin D2: One capsule weekly | Drug: 50K vitamin D2<br>* Supplement of vitamin D 400 units provided to all subjects, in addition Arm 1 will get placebo and Arm 2 will get D2 50K<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral Glucose Insulin Sensitivity (OGIS) | Oral glucose insulin sensitivity = index of insulin sensitivity, higher index means higher insulin sensitivity. Low insulin sensitivity means high insulin resistance and high risk of type 2 diabetes mellitus. It is calculated by a special formula using insulin and glucose measured in Oral Glucose Tolerance test. The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from oral glucose tolerance test) after 12 months of treatment calculated as OGIS at 12-months minus OGIS baseline. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline at 12 Months |  | Baseline and 12 Months | 
| Insulin Sensitivity by Matsuda Composite | Insulin Sensitivity by Matsuda Composite - index of insulin sensitivity, higher index means higher insulin sensitivity. Low insulin sensitivity means high insulin resistance and high risk of type 2 diabetes mellitus. It is calculated by a special formula using insulin and glucose measured in Oral Glucose Tolerance test. The formula is different from a formula for OGIS. Matsuda composite calculated based on formula 10^4/Square Root of [(fasting glucose x fasting insulin) x (mean glucose x mean insulin)] (Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic glucose clamp. Diabetes Care. 1999;22:1462-1470) Unit of measure is 10000/√[(µU/mL)/(mg/dL)]x[(µU/mL)/(mg/dL)]. | 12 Months | 
| Insulinogenic Index-30 | Index of insulin secretion, higher index means higher insulin secretion. It is calculated by a special formula using insulin and glucose measured at 0 min and at 30 min (hence 30 in the name) in Oral Glucose Tolerance test. Insulin secretion was assessed based on formula Insulinogenic index-30 [(insulin at 30 min - fasting insulin)/(glucose at 30 min - fasting glucose)] (Kosaka K, Hagura R, Kuzuya T. Insulin responses in equivocal and definite diabetes, with special reference to subjects who had mild glucose intolerance but later developed definite diabetes. Diabetes. 1977;26:944-952) | 12 Month | 
| C-Peptidogenic Index-30 | Index of insulin secretion, higher index means higher insulin secretion. C-peptide circulates in blood in amounts equal to insulin because insulin and C-peptide are linked when first made by the pancreas. C-peptide is more stable in blood than insulin; therefore it can be reliably used to evaluate insulin secretion. It is calculated by a special formula using C-peptide and glucose measured at 0 min and at 30 min (hence 30 in the name) in Oral Glucose Tolerance test. Insulin secretion was assessed based on formula C-Peptidogenic index-30 [(C-Peptide at 30 min - fasting C-peptide)/(glucose at 30 min - fasting glucose)]Bergstrom RW, Wahl PW, Leonetti DL, Fujimoto WY. Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance. J Clin Endocrinol Metab. 1990;71:1447-1453.) | 12 Month | 
| Incident Diabetes |  | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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African American men, Vitamin D, Glucose intolerance