Clinical trial NCT01942694: Vitamin D and Type 2 Diabetes Study
Official title: Vitamin D and Type 2 Diabetes Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetes
Type 2 Diabetes
Keywords: Prediabetes
Vitamin D
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Office of Dietary Supplements (ODS)
name: American Diabetes Association
First posted: 2013-09-16
Enrollment: 2423
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Pre-diabetes ("at increased risk for diabetes") defined by meeting 2-out-of-3 of the following glycemic criteria at the baseline visit:

   1. Fasting plasma glucose (FPG) 100-125 mg/dL
   2. 2-hour plasma glucose (2hPG) 140-199 mg/dL
   3. Hemoglobin A1c (HbA1c) 5.7-6.4%
2. Age ≥ 30 years .(≥25 years for people of the following races: American-Indian, Alaska Native, Native Hawaiian or Other Pacific Islander).
3. Body Mass Index ≥ 24.0 (22.5 for Asians) and ≤ 42.0 kg/m2
4. Provision of signed and dated written informed consent prior to any study procedures.

Major Exclusion Criteria:

1. Diabetes based on either of the following criteria:

   1. 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.
   2. Meeting the diagnosis criteria for diabetes
2. History (past 3 years) of hyperparathyroidism, nephrolithiasis or hypercalcemia.
3. 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.
4. Currently breastfeeding.

Primary outcomes:
measure: Time to Development of Diabetes
timeFrame: Approximately 48 months
Secondary outcomes:
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 25OHD Concentration
timeFrame: Approximately 48 months
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation)
timeFrame: Approximately 48 months
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria)
timeFrame: Approximately 48 months
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI
timeFrame: Approximately 48 months
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference
timeFrame: Approximately 48 months
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age
timeFrame: Approximately 48 months
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure)
timeFrame: Approximately 48 months
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements
timeFrame: Approximately 48 months
measure: Blood Plasma 25OHD Concentration.
timeFrame: Approximately 48 months
measure: Number of Participants With Adverse Events.
timeFrame: Approximately 48 months
measure: Change in Blood Pressure as a Continuous Variable.
timeFrame: Approximately 48 months
measure: Number of Participants Who Discontinue Study Pills.
timeFrame: Approximately 48 months
measure: Change in FPG as a Continuous Variable.
timeFrame: Every 12 months for approximately 48 months
measure: Change in 2hPG as a Continuous Variable.
timeFrame: Every 12 months for approximately 48 months.
measure: Change in HbA1c as a Continuous Variable.
timeFrame: Every 6 months for approximately 48 months
measure: Measurement of Insulin Resistance (Derived From the OGTT).
timeFrame: Every 12 months for approximately 48 months
measure: Measurement of Beta Cell Secretion (Derived From the OGTT)
timeFrame: Every 12 months for approximately 48 months
measure: Identification of Characteristics Associated With the Variability in Achieved 25OHD Concentration.
timeFrame: Every 12 months for approximately 48 months
Other outcomes:
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Sex
timeFrame: Approximately 48 months.
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Ethnicity
timeFrame: Approximately 48 months.
measure: Variability of Response to Vitamin D Supplementation by Baseline Characteristic: 2 Hour Plasma Glucose
timeFrame: Approximately 48 months
measure: Time to Development of Cancer.
timeFrame: Approximately 48 months.
measure: Time to Development of Cardiovascular Event.
timeFrame: Approximately 48 months.
measure: Incidence of Cancer in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria.
timeFrame: Approximately 48 months.
measure: Incidence of Cardiovascular Disease in a Pre-diabetes Population Defined by the Modern American Diabetes Association Criteria.
timeFrame: Approximately 48 months.
measure: 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).
timeFrame: One time assessment at the month 24 visit.
Locations:
city: Phoenix
country: United States
facility: Southwest American Indian Center
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Orlando
country: United States
facility: Orlando VA Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Translational Research Institute
state: Florida
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences
state: Louisiana
city: Scarborough
country: United States
facility: Maine Medical Center
state: Maine
city: Hyattsville
country: United States
facility: MedStar Community Clinical Research Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Health Partners Riverside Clinic
state: Minnesota
city: Omaha
country: United States
facility: Omaha VA Medical Center
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente Center for Health Research
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Tufts Medical Center
name: Anastassios Pittas, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.