Type 2 Diabetes
Conditions
Brief summary
This research study in adults with established type 2 diabetes will test whether daily vitamin D supplementation affects how the body processes glucose (sugar).
Interventions
DRUGCholecalciferol
DRUGPlacebo
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Established type 2 diabetes, defined by one of the following two criteria: * Age ≥ 25 years and ≤ 75 years * BMI: 23 to 40 kg/m2 inclusive * Provision of signed and dated written informed consent prior to any study procedures. Major
Exclusion criteria
* Severe diabetes defined by one of the following criteria: * \- (a) Symptoms of hyperglycemia; * \- (b) Screening HbA1c ≥ 7.5 \[may indicate potential for rapid progression during the trial necessitating need to amplify diabetes-specific pharmacotherapy\] * History of nephrolithiasis or hypercalcemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disposition Index | 6 months | Disposition index by the insulin secretion sensitivity index-2 (ISSI-2). This is an calculated value which represents the ability of a person's pancreatic beta cells to lower blood glucose. A higher number means the pancreas is better able to secrete insulin and improve glucose levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change in Glycemia | 12 months | Change in glycemia (categorical variable, composite outcome) defined as \[1\] a decrease in diabetes medications or \[2\] a reduction of equal to or more than 0.4 HbA1c units from baseline without increasing medications. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Variability of Response to Vitamin D Supplementation in Subgroups. | Baseline and 12 months | Variability of response to vitamin D supplementation in subgroups defined by baseline characteristics: (1) race; (3) 25OHD concentration; (3) diabetes treatment. |
| Effect of Vitamin D Supplementation on Blood 25-hydroxyvitaminD Concentration | 12 months | — |
| Hemoglobin A1c | 12 months | — |
| Effect of Vitamin D Supplementation on Plasma Concentrations of Surrogate Biomarkers of Cholesterol Absorption (Campesterol and β-sitosterol) and Endogenous Synthesis (Lathosterol and Desmosterol) | 6 months | — |
| Cardiovascular Risk Factors | 6 and 12 months | Cardiovascular risk factors defined as blood pressure, lipid profile, C-reactive protein and urine albumin excretion |
| Change in Diabetes Medications | 6 and 12 months | — |
Countries
United States
Participant flow
Pre-assignment details
127 participants were enrolled because by the time the 124 needed was reached, 3 additional participants were eligible and wanted to be part of the trial.
Participants by arm
| Arm | Count |
|---|---|
| Placebo One placebo pill daily for 1 year
Placebo | 61 |
| Cholecalciferol One cholecalciferol pill daily for 1 year
Cholecalciferol | 66 |
| Total | 127 |
Baseline characteristics
| Characteristic | Placebo | Cholecalciferol | Total |
|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 8.5 | 60.1 years STANDARD_DEVIATION 8.4 | 60.2 years STANDARD_DEVIATION 8.4 |
| Body Mass Index (BMI) | 31.2 kg/ m2 STANDARD_DEVIATION 3.8 | 30.7 kg/ m2 STANDARD_DEVIATION 3.9 | 30.9 kg/ m2 STANDARD_DEVIATION 3.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 60 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 17 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 38 Participants | 41 Participants | 79 Participants |
| Sex: Female, Male Female | 21 Participants | 17 Participants | 38 Participants |
| Sex: Female, Male Male | 40 Participants | 49 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 66 |
| other Total, other adverse events | 24 / 61 | 17 / 66 |
| serious Total, serious adverse events | 6 / 61 | 7 / 66 |
Outcome results
Primary
Disposition Index
Disposition index by the insulin secretion sensitivity index-2 (ISSI-2). This is an calculated value which represents the ability of a person's pancreatic beta cells to lower blood glucose. A higher number means the pancreas is better able to secrete insulin and improve glucose levels.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Disposition Index | 0.023 index | Standard Error 0.057 |
| Cholecalciferol | Disposition Index | 0.149 index | Standard Error 0.056 |
Secondary
Number of Participants With Change in Glycemia
Change in glycemia (categorical variable, composite outcome) defined as \[1\] a decrease in diabetes medications or \[2\] a reduction of equal to or more than 0.4 HbA1c units from baseline without increasing medications.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Change in Glycemia | 53 Participants |
| Cholecalciferol | Number of Participants With Change in Glycemia | 52 Participants |
Other Pre-specified
Cardiovascular Risk Factors
Cardiovascular risk factors defined as blood pressure, lipid profile, C-reactive protein and urine albumin excretion
Time frame: 6 and 12 months
Other Pre-specified
Change in Diabetes Medications
Time frame: 6 and 12 months
Other Pre-specified
Effect of Vitamin D Supplementation on Blood 25-hydroxyvitaminD Concentration
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effect of Vitamin D Supplementation on Blood 25-hydroxyvitaminD Concentration | 27.5 ng/mL | Standard Deviation 12 |
| Cholecalciferol | Effect of Vitamin D Supplementation on Blood 25-hydroxyvitaminD Concentration | 25.8 ng/mL | Standard Deviation 10.3 |
Other Pre-specified
Effect of Vitamin D Supplementation on Plasma Concentrations of Surrogate Biomarkers of Cholesterol Absorption (Campesterol and β-sitosterol) and Endogenous Synthesis (Lathosterol and Desmosterol)
Time frame: 6 months
Other Pre-specified
Hemoglobin A1c
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Hemoglobin A1c | 0.2 percentage | Standard Error 0.07 |
| Cholecalciferol | Hemoglobin A1c | 0.2 percentage | Standard Error 0.06 |
Other Pre-specified
Variability of Response to Vitamin D Supplementation in Subgroups.
Variability of response to vitamin D supplementation in subgroups defined by baseline characteristics: (1) race; (3) 25OHD concentration; (3) diabetes treatment.
Time frame: Baseline and 12 months