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Vitamin D and Type 2 Diabetes (Phoenix Site)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier:
NCT02015052
First received: December 13, 2013
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

Objectives:

People with low levels of vitamin D are at increased risk of developing type 2 diabetes. Supplementation with vitamin D may improve insulin sensitivity and insulin secretion, especially in those with prediabetes. However, no large clinical trial has demonstrated the ability of vitamin D supplementation to prevent or delay the onset of diabetes. The objective of the Vitamin D and type 2 diabetes study (D2d) is to determine whether vitamin D3 supplementation will decrease the risk of type 2 diabetes. D2d will evaluate, in 2382 people study-wide (150 at the Phoenix site), whether supplementation with vitamin D3 will prevent progression to type 2 diabetes in a high-risk population, compared with placebo.

Study Population:

American Indians are at a disproportionate risk for developing type 2 diabetes and carry a disproportionate burden of disease as a result. The Phoenix site of D2d will recruit American Indian participants exclusively, to ensure representation by this population. Potential participants will be eligible if they do not have diabetes, have a BMI at least 25 kg/m2, and meet at least two out of three criteria for pre-diabetes (fasting plasma glucose 100-125 mg/dl, 2-hour plasma glucose 140-199 mg/dl, and HbA1c 5.7-6.4%). Exclusion criteria include any condition that would increase the risk of complications due to vitamin D3 supplementation (e.g., history of kidney stones, hypercalcemia, or intolerance to vitamin D3 supplements).

Design:

Participants eligible for D2d will be randomly assigned to either vitamin D3 supplementation (4,000 international units daily by mouth) or placebo. Participants and staff will be blinded to treatment assignment. Both intervention groups will be offered education on lifestyle changes to prevent diabetes.

Participants will be followed every 6 months at a formal clinic visit at which blood will be drawn for fasting glucose and HbA1c. At annual visits a 75-gm 2-hour oral glucose tolerance test will also be done.

Outcome Parameters:

The primary outcome of the study will be time to onset of type 2 diabetes. Diabetes will be diagnosed if a participant has a fasting plasma glucose of at least 126 mg/dl, a 2-hour glucose of at least 200 mg/dl, or a HbA1c of at least 6.5%, confirmed. Secondary outcomes will include variability in response to vitamin D3 supplementation by baseline characteristics and by adherence to the intervention.


Condition Intervention Phase
Type 2 Diabetes
Dietary Supplement: Vitamin D3 Supplementation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin D and Type 2 Diabetes (Phoenix Site)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Time to development of type 2 diabetes in those who receive vs did not receive vitamin D3 supplementation [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Variability of response to vitamin D3 supplementation by baseline characteristics: race/ethnicity, BMI, age, geographic location, dietary calcium intake, baseline 250OD concentration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Variability of response to vitamin D3 supplementation by adherence based on pill counts and by acheived 25OHD concentration. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: November 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active Vitamin D Dietary Supplement: Vitamin D3 Supplementation
N/A

Detailed Description:

Objectives:

People with low levels of vitamin D are at increased risk of developing type 2 diabetes. Supplementation with vitamin D may improve insulin sensitivity and insulin secretion, especially in those with prediabetes. However, no large clinical trial has demonstrated the ability of vitamin D supplementation to prevent or delay the onset of diabetes. The objective of the Vitamin D and type 2 diabetes study (D2d) is to determine whether vitamin D3 supplementation will decrease the risk of type 2 diabetes. D2d will evaluate, in 2382 people study-wide (150 at the Phoenix site), whether supplementation with vitamin D3 will prevent progression to type 2 diabetes in a high-risk population, compared with placebo.

Study Population:

American Indians are at a disproportionate risk for developing type 2 diabetes and carry a disproportionate burden of disease as a result. The Phoenix site of D2d will recruit American Indian participants exclusively, to ensure representation by this population. Potential participants will be eligible if they do not have diabetes, have a BMI at least 25 kg/m2, and meet at least two out of three criteria for pre-diabetes (fasting plasma glucose 100-125 mg/dl, 2-hour plasma glucose 140-199 mg/dl, and HbA1c 5.7-6.4%). Exclusion criteria include any condition that would increase the risk of complications due to vitamin D3 supplementation (e.g., history of kidney stones, hypercalcemia, or intolerance to vitamin D3 supplements).

Design:

Participants eligible for D2d will be randomly assigned to either vitamin D3 supplementation (4,000 international units daily by mouth) or placebo. Participants and staff will be blinded to treatment assignment. Both intervention groups will be offered education on lifestyle changes to prevent diabetes.

Participants will be followed every 6 months at a formal clinic visit at which blood will be drawn for fasting glucose and HbA1c. At annual visits a 75-gm 2-hour oral glucose tolerance test will also be done.

Outcome Parameters:

The primary outcome of the study will be time to onset of type 2 diabetes. Secondary outcomes will include variability in response to vitamin D3 supplementation by baseline characteristics and by adherence to the intervention.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

    1. -Pre-diabetes (at increased risk for diabetes) defined by meeting 2-out-of-3 of the following glycemic criteria, established by the ADA in the 2010 clinical practice guidelines, at the baseline visit:

      --FPG 100-125 mg/dL, inclusive

      • 2hPG 140-199 mg/dL, inclusive
      • HbA1c 5.7-6.4%, inclusive
    2. -Age greater than or equal to 30 years. Age is a major risk factor for type 2 diabetes; avoid contamination with type 1 Diabetes or Latent Autoimmune Diabetes of Adults, conditions that have a different pathophysiology; minimize loss to follow-up due to social mobility; facilitate recruitment and increase applicability of findings
    3. -BMI greater than or equal to 25.0 (23.0 for Asians) and less than or equal to 40.0 kg/m(2). Overweight/obesity is a major risk factor for type 2 diabetes; those with severe obesity require higher doses of vitamin D
    4. -Provision of signed and dated written informed consent prior to any study procedures.

      EXCLUSION CRITERIA:

      Exclusion Criteria were selected to: (1) ensure participants safety; (2) avoid conditions that would affect the outcomes (i.e. minimize competing risk); (3) make recruitment targets realistic; (4) amplify generalizability of study results; (5) maximize participants adherence with study procedures.

    5. -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 glycemic criteria for diabetes, as defined by the ADA guidelines (FPG greater than or equal to 126 mg/dL, 2hPG greater than or equal to 200 mg/dL or HbA1c greater than or equal to 6.5%).
    6. -History (past 3 years) of hyperparathyroidism, nephrolithiasis or hypercalcemia.
    7. -Any medical condition (past 3 years) that in the opinion of the site investigator may increase risk for nephrolithiasis or hypercalcemia during the trial (e.g. sarcoidosis).
    8. -Use of tanning devices within 12 weeks of the baseline visit and unwilling to stop using tanning devices for the duration of the study interference with intervention

      Medications and Supplements:

    9. -Use of supplements containing vitamin D at total doses higher than 1000 IU/day within 12 weeks of the baseline visit initiating the protocol and unwillingness to limit vitamin D supplementation dosage to no higher than 1000 IU/day for the duration of the study.
    10. -Use of supplements containing calcium at total doses higher than 600 mg/day within 1 week of the baseline visit initiating the protocol and unwillingness to limit calcium supplementation dosage to no more than 600 mg/day for the duration of the study.
    11. -Current use of medications or conditions (e.g. untreated celiac disease) that would interfere with absorption or metabolism of vitamin D.
    12. -Current use of medications approved by the FDA for weight management.
    13. -Use of thiazide diuretics at a total dose greater than 37.5 mg/day.
    14. Use of anticonvulsant drug started within 6 months of screening. Stable regimen of anticonvulsants is allowed.
    15. -History of intolerance to vitamin D supplements.

      Other Medical History:

    16. -Severe symptomatic cardiovascular disease based on history and physical examination (unstable angina, dyspnea on exertion, paroxysmal nocturnal dyspnea, arrhythmia, congestive heart failure NYHA class II or higher, claudication).
    17. -History (past 1 year) of myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft.
    18. -History (past 1 year) of cerebrovascular disease (stroke, transient ischemic attack). 19-.-Any type of cancer (past 5 years) except for basal cell skin cancer. Participants with prostate cancer (for men over age 55) or well-differentiated thyroid cancer that are not expected to require treatment (except for suppression with thyroid hormone) over the next 4 years are not excluded.

    20.-History (past 6 months) of treatment with oral (for > 7 days) or intravenous glucocorticoids or disease likely to require oral or intravenous glucocorticoid therapy during the study (inhaled glucocorticoids are not excluded). Interference with outcome assessment

    21.-History (past 1 year) of substance abuse or unstable psychiatric disorder that in the opinion of the site investigator would impede competence or adherence with study procedures or hinder completion of the study or increase risk. Use of marijuana with a medical prescription is permitted.

    22.-History of bariatric surgery or planned bariatric surgery in the next 4 years. Participants with gastric banding more than 2 years ago with self-reported weight stability (defined as weight change no greater than 3 kg during the prior 6 months) are not excluded. Interfere with vitamin D absorption.

    23.-A life-threatening event within 30 days of screening or currently planned major surgery.

    24.-Any other unstable active medical condition (including but not limited to liver disease, wasting illness, AIDS, tuberculosis, oxygen-dependent chronic obstructive pulmonary disease, organ transplant, Cushing s syndrome) that in the opinion of the site investigators would impede competence or adherence with study procedures or increase risk.Aadherence, plasma 25OHD may decrease as an acute-phase response. Such conditions will be assessed based on self-report and/or review of medical records (if available).

    25.-Uncontrolled hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg).

    26.-Poor venous access.

Laboratory Evaluation:

27.-Serum liver transaminase (ALT or AST) higher than 3 times the normal range for the clinical site s laboratory

28.-Anemia (hematocrit < 32 for women, < 36 for men), whole blood transfusion (within 6 months of screening) or chronic requirement, whole blood donation (within 3 months of screening) or other condition (hemolysis, hemoglobinopathy) rendering HbA1c results unreliable as indicator of chronic glycemia. Interference with outcome assessment. Participants who donate platelets are not excluded. Whole blood transfusion or donation does not exclude participant, but screening and study visits need to be timed appropriately.

29.-Low platelet count (< 50,000). Safety for blood draws

30.-Chronic kidney disease, defined as estimated glomerular filtration rate GFR < 50 mL/min, from creatinine measured at the clinical site s laboratory and GFR calculated centrally. Vitamin D homeostasis changes as GFR declines. These changes start when GFR falls around 40-60 mL/min per 1.73 m(2). The planning committee selected 50 mL/min as the exclusion cutoff to ensure that participants maintain GFR > 40 mL/min during the study. Please note: to prevent potential confusion, GFR units will be denoted as mL/min throughout the protocol and associated documents.

31.-Hypercalcemia, defined as serum calcium concentration greater than or equal to the upper limit of normal, measured at the clinical site s laboratory.

Hypercalciuria, defined as spot urine (morning void) calcium-creatinine ratio > 0.275.

Other

33.-Participation (within 30 days of screening) in another interventional research study.

34.-Previous randomization in the D2d study. Participants who did not qualify after screening may be screened again if the prior reason for exclusion has been addressed (e.g. high blood pressure is treated).

35.-Any other reason that in the opinion of the site investigator would impede adherence with study procedures or hinder completion of the study or increase risk (e.g. use of non-approved or experimental drugs, inability to follow instructions or understand the informed consent, dementia, unable to remain in the program for the duration of the study, inability to comply with the study protocol for any reason).

Women only

36.-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.

37.-Currently breastfeeding.

38.-Use of oral contraceptives or menopausal hormone therapy started within 3 months of baseline. Stable regimen of oral contraceptives or any other hormonal method of contraception (e.g. implantable) is allowed.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02015052

Contacts
Contact: Jennifer Weil, M.D. Not Listed
Contact: William C Knowler, M.D. (602) 200-5206 wknowler@phx.niddk.nih.gov

Locations
United States, Arizona
NIDDK, Phoenix Not yet recruiting
Phoenix, Arizona, United States, 85014
Sponsors and Collaborators
Investigators
Principal Investigator: William C Knowler, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier: NCT02015052     History of Changes
Other Study ID Numbers: 999914025, 14-DK-N025
Study First Received: December 13, 2013
Last Updated: August 29, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Type 2 Diabetes Mellitus
Vitamin D
Prevention

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014