Back to resultsVitamin D and Type 2 Diabetes Study (D2d)
Primary Purpose
Prediabetes, Type 2 Diabetes
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vitamin D (Cholecalciferol)
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Prediabetes focused on measuring Prediabetes, Vitamin D
Eligibility Criteria
Inclusion Criteria:
Pre-diabetes ("at increased risk for diabetes") defined by meeting 2-out-of-3 of the following glycemic criteria at the baseline visit:
- Fasting plasma glucose (FPG) 100-125 mg/dL
- 2-hour plasma glucose (2hPG) 140-199 mg/dL
- Hemoglobin A1c (HbA1c) 5.7-6.4%
- Age ≥ 30 years .(≥25 years for people of the following races: American-Indian, Alaska Native, Native Hawaiian or Other Pacific Islander).
- Body Mass Index ≥ 24.0 (22.5 for Asians) and ≤ 42.0 kg/m2
- Provision of signed and dated written informed consent prior to any study procedures.
Major Exclusion Criteria:
Diabetes based on either of the following criteria:
- History (past 1 year) of hypoglycemic pharmacotherapy (oral or injectable medication approved by the FDA for type 2 diabetes), used for any condition (e.g. pre-diabetes, diabetes, polycystic ovarian syndrome.
- Meeting the diagnosis criteria for diabetes
- History (past 3 years) of hyperparathyroidism, nephrolithiasis or hypercalcemia.
- Pregnancy (past 1 year by report or positive pregnancy test at screening), intent to become pregnant in the next 4 years or unprotected intercourse. History of gestational diabetes is not an exclusion criterion.
- Currently breastfeeding.
Sites / Locations
- Southwest American Indian Center
- University of Southern California
- Stanford University
- University of Colorado, Denver
- Orlando VA Medical Center
- Florida Hospital Translational Research Institute
- Atlanta VA Medical Center
- Northwestern University
- University of Kansas Medical Center
- Pennington Biomedical Research Center
- Tulane University Health Sciences
- Maine Medical Center
- MedStar Community Clinical Research Center
- Tufts Medical Center
- Health Partners Riverside Clinic
- Omaha VA Medical Center
- University of Nebraska Medical Center
- Beth Israel Medical Center
- Duke University
- Cleveland Clinic
- Kaiser Permanente Center for Health Research
- Medical University of South Carolina
- University of Tennessee Health Science Center
- University of Texas Southwestern Medical Center
- Baylor College of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
Vitamin D (Cholecalciferol)
Arm Description
One pill daily
One vitamin D pill daily
Outcomes
Primary Outcome Measures
Time to Development of Diabetes
New-onset diabetes was based on annual glycemic testing of fasting plasma glucose, glycated hemoglobin, and 2-hour post-load plasma glucose and semiannual testing of fasting plasma glucose and glycated hemoglobin. If two or three of the glycemic measures met the 2010 ADA thresholds for diabetes, the participant was considered to have met the diabetes outcome. When only the measure for fasting plasma glucose or glycated hemoglobin met the threshold, confirmatory testing was performed for the positive measure within 8 weeks. If only the measure for 2-hour post-load plasma glucose met the threshold, then a 75-g oral glucose tolerance test to reassess all three glycemic measures was repeated. If the repeat measure was positive or both fasting plasma glucose and glycated hemoglobin were positive (in the case of a repeat oral glucose tolerance test), than the participant was considered to have met the diabetes outcome.
Secondary Outcome Measures
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 25OHD Concentration
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation)
Race and ethnic group were reporting by the participant. The category "other" includes American Indian or Alaska Native; Native Hawaiian or other Pacific Islander; and other race. Ethnic group includes any race.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria)
Participants met at least two of three glycemic criteria for prediabetes: fasting plasma glucose level, 100 to 125 mg per deciliter (5.6 to 6.9 mmol per liter); plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter (7.8 to 11.0 mmol per liter) (impaired glucose tolerance); and glycated hemoglobin level, 5.7 to 6.4% (39 to 47 mmol per mole).
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure)
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements
Blood Plasma 25OHD Concentration.
Number of Participants With Adverse Events.
Change in Blood Pressure as a Continuous Variable.
Number of Participants Who Discontinue Study Pills.
Change in FPG as a Continuous Variable.
Change in 2hPG as a Continuous Variable.
Change in HbA1c as a Continuous Variable.
Measurement of Insulin Resistance (Derived From the OGTT).
Measurement of Beta Cell Secretion (Derived From the OGTT)
Identification of Characteristics Associated With the Variability in Achieved 25OHD Concentration.
Full Information
NCT ID
NCT01942694
First Posted
August 9, 2013
Last Updated
July 22, 2022
Sponsor
Tufts Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Office of Dietary Supplements (ODS), American Diabetes Association
1. Study Identification
Unique Protocol Identification Number
NCT01942694
Brief Title
Vitamin D and Type 2 Diabetes Study
Acronym
D2d
Official Title
Vitamin D and Type 2 Diabetes Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
November 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Office of Dietary Supplements (ODS), American Diabetes Association
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The goal of the Vitamin D and type 2 diabetes (D2d) study is to determine if vitamin D supplementation works to delay the onset of type 2 diabetes in people at risk for the disease and to gain a better understand how vitamin D affects glucose (sugar) metabolism.
Detailed Description
The goal of the Vitamin D and type 2 diabetes (D2d) study is to determine if vitamin D supplementation works to delay the onset of type 2 diabetes in people at risk for the disease and to gain a better understand how vitamin D affects glucose (sugar) metabolism. Researchers at US sites will enroll people with pre-diabetes (people who have higher than normal blood glucose level but not high enough to meet the diagnosis of diabetes). The study will enroll participants over approximately 2 years and participants will be followed for approximately 3 years. Participants will receive either Vitamin D or a placebo by chance. Participants will take 1 pill a day for the duration of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prediabetes, Type 2 Diabetes
Keywords
Prediabetes, Vitamin D
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2423 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One pill daily
Arm Title
Vitamin D (Cholecalciferol)
Arm Type
Active Comparator
Arm Description
One vitamin D pill daily
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D (Cholecalciferol)
Intervention Description
Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Administered as one soft-gel pill daily by mouth
Primary Outcome Measure Information:
Title
Time to Development of Diabetes
Description
New-onset diabetes was based on annual glycemic testing of fasting plasma glucose, glycated hemoglobin, and 2-hour post-load plasma glucose and semiannual testing of fasting plasma glucose and glycated hemoglobin. If two or three of the glycemic measures met the 2010 ADA thresholds for diabetes, the participant was considered to have met the diabetes outcome. When only the measure for fasting plasma glucose or glycated hemoglobin met the threshold, confirmatory testing was performed for the positive measure within 8 weeks. If only the measure for 2-hour post-load plasma glucose met the threshold, then a 75-g oral glucose tolerance test to reassess all three glycemic measures was repeated. If the repeat measure was positive or both fasting plasma glucose and glycated hemoglobin were positive (in the case of a repeat oral glucose tolerance test), than the participant was considered to have met the diabetes outcome.
Time Frame
Approximately 48 months
Secondary Outcome Measure Information:
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 25OHD Concentration
Time Frame
Approximately 48 months
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation)
Description
Race and ethnic group were reporting by the participant. The category "other" includes American Indian or Alaska Native; Native Hawaiian or other Pacific Islander; and other race. Ethnic group includes any race.
Time Frame
Approximately 48 months
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria)
Description
Participants met at least two of three glycemic criteria for prediabetes: fasting plasma glucose level, 100 to 125 mg per deciliter (5.6 to 6.9 mmol per liter); plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter (7.8 to 11.0 mmol per liter) (impaired glucose tolerance); and glycated hemoglobin level, 5.7 to 6.4% (39 to 47 mmol per mole).
Time Frame
Approximately 48 months
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI
Time Frame
Approximately 48 months
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference
Time Frame
Approximately 48 months
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age
Time Frame
Approximately 48 months
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure)
Time Frame
Approximately 48 months
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements
Time Frame
Approximately 48 months
Title
Blood Plasma 25OHD Concentration.
Time Frame
Approximately 48 months
Title
Number of Participants With Adverse Events.
Time Frame
Approximately 48 months
Title
Change in Blood Pressure as a Continuous Variable.
Time Frame
Approximately 48 months
Title
Number of Participants Who Discontinue Study Pills.
Time Frame
Approximately 48 months
Title
Change in FPG as a Continuous Variable.
Time Frame
Every 12 months for approximately 48 months
Title
Change in 2hPG as a Continuous Variable.
Time Frame
Every 12 months for approximately 48 months.
Title
Change in HbA1c as a Continuous Variable.
Time Frame
Every 6 months for approximately 48 months
Title
Measurement of Insulin Resistance (Derived From the OGTT).
Time Frame
Every 12 months for approximately 48 months
Title
Measurement of Beta Cell Secretion (Derived From the OGTT)
Time Frame
Every 12 months for approximately 48 months
Title
Identification of Characteristics Associated With the Variability in Achieved 25OHD Concentration.
Time Frame
Every 12 months for approximately 48 months
Other Pre-specified Outcome Measures:
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Sex
Time Frame
Approximately 48 months.
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Ethnicity
Time Frame
Approximately 48 months.
Title
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 2 Hour Plasma Glucose
Time Frame
Approximately 48 months
Title
Time to Development of Cancer.
Time Frame
Approximately 48 months.
Title
Time to Development of Cardiovascular Event.
Time Frame
Approximately 48 months.
Title
Incidence of Cancer in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria.
Time Frame
Approximately 48 months.
Title
Incidence of Cardiovascular Disease in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria.
Time Frame
Approximately 48 months.
Title
Quality of Life and Mood Scores in Pre-diabetes Population Using a Validated Instrument (PROMIS-29 Profile v2.0 and a General Question on Perception of Overall Health From the PROMIS Scale 1.2).
Time Frame
One time assessment at the month 24 visit.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pre-diabetes ("at increased risk for diabetes") defined by meeting 2-out-of-3 of the following glycemic criteria at the baseline visit:
Fasting plasma glucose (FPG) 100-125 mg/dL
2-hour plasma glucose (2hPG) 140-199 mg/dL
Hemoglobin A1c (HbA1c) 5.7-6.4%
Age ≥ 30 years .(≥25 years for people of the following races: American-Indian, Alaska Native, Native Hawaiian or Other Pacific Islander).
Body Mass Index ≥ 24.0 (22.5 for Asians) and ≤ 42.0 kg/m2
Provision of signed and dated written informed consent prior to any study procedures.
Major Exclusion Criteria:
Diabetes based on either of the following criteria:
History (past 1 year) of hypoglycemic pharmacotherapy (oral or injectable medication approved by the FDA for type 2 diabetes), used for any condition (e.g. pre-diabetes, diabetes, polycystic ovarian syndrome.
Meeting the diagnosis criteria for diabetes
History (past 3 years) of hyperparathyroidism, nephrolithiasis or hypercalcemia.
Pregnancy (past 1 year by report or positive pregnancy test at screening), intent to become pregnant in the next 4 years or unprotected intercourse. History of gestational diabetes is not an exclusion criterion.
Currently breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anastassios Pittas, MD, MS
Organizational Affiliation
Tufts Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest American Indian Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Colorado, Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Orlando VA Medical Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Florida Hospital Translational Research Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Atlanta VA Medical Center
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Pennington Biomedical Research Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Tulane University Health Sciences
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Maine Medical Center
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
MedStar Community Clinical Research Center
City
Hyattsville
State/Province
Maryland
ZIP/Postal Code
20782
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Health Partners Riverside Clinic
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Facility Name
Omaha VA Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68105
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Beth Israel Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27704
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Kaiser Permanente Center for Health Research
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Tennessee Health Science Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35753926
Citation
Desouza C, Chatterjee R, Vickery EM, Nelson J, Johnson KC, Kashyap SR, Lewis MR, Margolis K, Pratley R, Rasouli N, Sheehan PR, Pittas AG; D2d Research Group. Electronic address: d2d@tuftsmedicalcenter.org. The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study. J Diabetes Complications. 2022 Aug;36(8):108230. doi: 10.1016/j.jdiacomp.2022.108230. Epub 2022 Jun 12.
Results Reference
derived
PubMed Identifier
35140313
Citation
Johnson KC, Pittas AG, Margolis KL, Peters AL, Phillips LS, Vickery EM, Nelson J, Sheehan PR, Reboussin D, Malozowski S, Chatterjee R; D2d research group. Safety and tolerability of high-dose daily vitamin D3 supplementation in the vitamin D and type 2 diabetes (D2d) study-a randomized trial in persons with prediabetes. Eur J Clin Nutr. 2022 Aug;76(8):1117-1124. doi: 10.1038/s41430-022-01068-8. Epub 2022 Feb 9. Erratum In: Eur J Clin Nutr. 2022 Apr 13;:
Results Reference
derived
PubMed Identifier
33693713
Citation
Chatterjee R, Fuss P, Vickery EM, LeBlanc ES, Sheehan PR, Lewis MR, Dolor RJ, Johnson KC, Kashyap SR, Nelson J, Pittas AG; D2d Research Group. Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study. J Clin Endocrinol Metab. 2021 Aug 18;106(9):2767-2778. doi: 10.1210/clinem/dgab153.
Results Reference
derived
PubMed Identifier
31965161
Citation
Hsia DS, Rasouli N, Pittas AG, Lary CW, Peters A, Lewis MR, Kashyap SR, Johnson KC, LeBlanc ES, Phillips LS, Hempe JM, Desouza CV; D2d Research Group. Implications of the Hemoglobin Glycation Index on the Diagnosis of Prediabetes and Diabetes. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e130-8. doi: 10.1210/clinem/dgaa029.
Results Reference
derived
PubMed Identifier
31173679
Citation
Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O'Neil P, Park J, Peters A, Phillips LS, Pratley R, Raskin P, Rasouli N, Robbins D, Rosen C, Vickery EM, Staten M; D2d Research Group. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med. 2019 Aug 8;381(6):520-530. doi: 10.1056/NEJMoa1900906. Epub 2019 Jun 7.
Results Reference
derived
PubMed Identifier
31007049
Citation
Aroda VR, Sheehan PR, Vickery EM, Staten MA, LeBlanc ES, Phillips LS, Brodsky IG, Chadha C, Chatterjee R, Ouellette MG, Desouza C, Pittas AG; D2d Research Group. Establishing an electronic health record-supported approach for outreach to and recruitment of persons at high risk of type 2 diabetes in clinical trials: The vitamin D and type 2 diabetes (D2d) study experience. Clin Trials. 2019 Jun;16(3):306-315. doi: 10.1177/1740774519839062. Epub 2019 Apr 22.
Results Reference
derived
PubMed Identifier
29941495
Citation
LeBlanc ES, Pratley RE, Dawson-Hughes B, Staten MA, Sheehan PR, Lewis MR, Peters A, Kim SH, Chatterjee R, Aroda VR, Chadha C, Neff LM, Brodsky IG, Rosen C, Desouza CV, Foreyt JP, Hsia DS, Johnson KC, Raskin P, Kashyap SR, O'Neil P, Phillips LS, Rasouli N, Liao EP, Robbins DC, Pittas AG; D2d Research Group. Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts. Diabetes Care. 2018 Aug;41(8):1590-1599. doi: 10.2337/dc18-0240. Epub 2018 Jun 25. Erratum In: Diabetes Care. 2019 Dec;42(12):2347.
Results Reference
derived
PubMed Identifier
27899488
Citation
Lewis MR, Macauley RC, Sheehan PR, Staten MA, Phillips LS, Rasouli N, Pittas AG; D2d Research Group. Management of Hemoglobin Variants Detected Incidentally in HbA1c Testing: A Common Problem Currently Lacking a Standard Approach. Diabetes Care. 2017 Feb;40(2):e8-e9. doi: 10.2337/dc16-1667. Epub 2016 Nov 29. No abstract available.
Results Reference
derived
PubMed Identifier
25205139
Citation
Pittas AG, Dawson-Hughes B, Sheehan PR, Rosen CJ, Ware JH, Knowler WC, Staten MA; D2d Research Group. Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial. Diabetes Care. 2014 Dec;37(12):3227-34. doi: 10.2337/dc14-1005. Epub 2014 Sep 9.
Results Reference
derived
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Vitamin D and Type 2 Diabetes Study
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