Vitamin D and Type 2 Diabetes (Phoenix Site)

Last updated: June 4, 2015
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Overall Status: Active - Not Recruiting

Phase

3

Condition

Diabetes Mellitus, Type 2

Diabetes And Hypertension

Diabetes Mellitus Types I And Ii

Treatment

N/A

Clinical Study ID

NCT02015052
999914025
14-DK-N025
  • Ages > 30
  • Both
  • Accepts Healthy Volunteers

Study Summary

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.

Eligibility Criteria

Inclusion

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

--FPG 100-125 mg/dL, inclusive

  • 2hPG 140-199 mg/dL, inclusive

  • HbA1c 5.7-6.4%, inclusive

  1. -Age greater than or equal to 30 years. Age is a major risk factor for type 2diabetes; avoid contamination with type 1 Diabetes or Latent Autoimmune Diabetesof Adults, conditions that have a different pathophysiology; minimize loss tofollow-up due to social mobility; facilitate recruitment and increaseapplicability of findings

  2. -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

  3. -Provision of signed and dated written informed consent prior to any studyprocedures.

Exclusion

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 studyresults; (5) maximize participants adherence with study procedures.

  1. -Diabetes based on either of the following criteria:

  • History (past 1 year) of hypoglycemic pharmacotherapy (oral or injectablemedication 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 200mg/dL or HbA1c greater than or equal to 6.5%).

  1. -History (past 3 years) of hyperparathyroidism, nephrolithiasis orhypercalcemia.

  2. -Any medical condition (past 3 years) that in the opinion of the siteinvestigator may increase risk for nephrolithiasis or hypercalcemia during thetrial (e.g. sarcoidosis).

  3. -Use of tanning devices within 12 weeks of the baseline visit and unwilling tostop using tanning devices for the duration of the study interference withintervention Medications and Supplements:

  4. -Use of supplements containing vitamin D at total doses higher than 1000 IU/daywithin 12 weeks of the baseline visit initiating the protocol and unwillingnessto limit vitamin D supplementation dosage to no higher than 1000 IU/day for theduration of the study.

  5. -Use of supplements containing calcium at total doses higher than 600 mg/daywithin 1 week of the baseline visit initiating the protocol and unwillingness tolimit calcium supplementation dosage to no more than 600 mg/day for the durationof the study.

  6. -Current use of medications or conditions (e.g. untreated celiac disease) thatwould interfere with absorption or metabolism of vitamin D.

  7. -Current use of medications approved by the FDA for weight management.

  8. -Use of thiazide diuretics at a total dose greater than 37.5 mg/day.

  9. Use of anticonvulsant drug started within 6 months of screening. Stable regimenof anticonvulsants is allowed.

  10. -History of intolerance to vitamin D supplements. Other Medical History:

  11. -Severe symptomatic cardiovascular disease based on history and physicalexamination (unstable angina, dyspnea on exertion, paroxysmal nocturnal dyspnea,arrhythmia, congestive heart failure NYHA class II or higher, claudication).

  12. -History (past 1 year) of myocardial infarction, percutaneous coronaryintervention or coronary artery bypass graft.

  13. -History (past 1 year) of cerebrovascular disease (stroke, transient ischemicattack). 19-.-Any type of cancer (past 5 years) except for basal cell skincancer. Participants with prostate cancer (for men over age 55) orwell-differentiated thyroid cancer that are not expected to require treatment (except for suppression with thyroid hormone) over the next 4 years are notexcluded.

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

21.-History (past 1 year) of substance abuse or unstable psychiatric disorder that inthe opinion of the site investigator would impede competence or adherence with studyprocedures or hinder completion of the study or increase risk. Use of marijuana witha 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 weightstability (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 majorsurgery.

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

25.-Uncontrolled hypertension (systolic blood pressure > 160 mm Hg or diastolicblood 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 theclinical site s laboratory

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

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

30.-Chronic kidney disease, defined as estimated glomerular filtration rate GFR < 50mL/min, from creatinine measured at the clinical site s laboratory and GFR calculatedcentrally. Vitamin D homeostasis changes as GFR declines. These changes start when GFRfalls around 40-60 mL/min per 1.73 m(2). The planning committee selected 50 mL/min as theexclusion 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/minthroughout the protocol and associated documents.

31.-Hypercalcemia, defined as serum calcium concentration greater than or equal to theupper 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 afterscreening 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 adherencewith study procedures or hinder completion of the study or increase risk (e.g. use ofnon-approved or experimental drugs, inability to follow instructions or understand theinformed 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 tobecome pregnant in the next 4 years or unprotected intercourse. History of gestationaldiabetes is not an exclusion criterion.

37.-Currently breastfeeding.

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

Study Design

Total Participants: 300
Study Start date:
November 01, 2013
Estimated Completion Date:
December 31, 2017

Study 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.

Connect with a study center

  • NIDDK, Phoenix

    Phoenix, Arizona 85014
    United States

    Site Not Available

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