Effect of Vitamin D Supplementation on Glucose Tolerance in Subjects at Risk for Diabetes With Low Vitamin D. (EVIDENCE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Toronto
Sponsor:
Collaborators:
Dairy Farmers of Canada
Public Health Agency of Canada (PHAC)
Information provided by (Responsible Party):
Thomas Wolever, University of Toronto
ClinicalTrials.gov Identifier:
NCT01726777
First received: November 9, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

Type 2 diabetes (T2D) is an increasingly common and serious condition. Studies show that low vitamin D levels are associated with increased diabetes risk and that vitamin D may protect against diabetes by reducing chronic inflammation and improving insulin sensitivity and insulin secretion. However, no studies have been able to show that vitamin D actually reduces post-prandial blood glucose levels, the most clinically relevant marker of diabetes. Previously the investigators have shown that cheddar cheese and low-fat cheese can be fortified with high levels of vitamin D and that this cheese is at least as a effective as vitamin D supplements in raising blood vitamin D levels.

The main purpose of this study is to see whether vitamin D enriched cheese can improve oral glucose tolerance (reduce blood glucose 2 hours after consuming a drink containing 75g sugar) in people who have low vitamin D levels and are at risk for developing T2D.

Other aims are to determine the effect of vitamin D may on insulin sensitivity, insulin secretion, markers of inflammation, blood cholesterol levels, and safety markers such as urinary calcium excretion.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Vitamin D Deficiency
Dietary Supplement: Control
Dietary Supplement: Vitamin D
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Vitamin D Supplementation on Oral Glucose Tolerance in Subjects Exhibiting Marginal Vitamin D Status and an Increased Risk of Developing Diabetes.

Resource links provided by NLM:


Further study details as provided by University of Toronto:

Primary Outcome Measures:
  • Change in plasma glucose concentration 2 hours after consuming 75g oral glucose (2 hour PC glucose, or 2hrPC glucose) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Change from baseline in plasma glucose concentration 2 hours after consuming 75g oral glucose.


Secondary Outcome Measures:
  • Change in insulin resistance assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR) which is G*I/22.5 where G is fasting plasma glucose (mmol/L) and I is fasting plasma insulin (uU/mL).

  • Change in Matsuda insulin sensitivity index [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in Matsuda insulin sensitivity index which is (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]).

  • Change in insulin secretion assessed using the homeostasis model assessment of beta-cell function (HOMA-B) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in homeostasis model assessment of beta-cell function (HOMA-B) which is 20*I/(G-3.5) where I is fasting plasma insulin (uU/mL) and G is fasting plasma glucose (mmol/L).

  • Change in insulinogenic index [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in insulinogenic index which is dI0-30/dG0-30, where dI0-30 is the change in plasma insulin between fasting and 30min and dG0-30 is the change in plasma glucose between fasting and 30min after 75g oral glucose.

  • Change in disposition index derived from HOMA-IR and HOMA-B [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in disposition index which is HOMA-B/HOMA-IR, which have been defined above.

  • Change in disposition index based on oral glucose tolerance test (OGTT) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in ISSI-2 index which is AUCi/AUCg x Matsuda insulin sensitivity index, where AUCi and AUCg, respectively, are the total areas under the plasma insulin and glucose response curves after 75g oral glucose and Matsuda insulin sensitivity index has been defined above.

  • Change in fasting plasma glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting plasma glucose

  • Change in glucose area under the curve [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in incremental area under the glucose response curve after 75g oral glucose

  • Change in glycated hemoglobin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in glycated hemoglobin (HbA1c)

  • Correlation between changes in serum 25-hydroxy-vitamin D concentration (25(OH)D) and changes in 2 hour PC glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Correlation between change from baseline in serum 25-hydroxy-vitamin D concentration and change from baseline in plasma glucose 2 hours after 75g oral glucose.


Other Outcome Measures:
  • Fasting serum 25(OH)D [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Absolute concentration of serum 25-hydroxy-vitamin D3

  • Change in serum 25(OH)D [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in serum 25-hydroxy-vitamin D3

  • Change in serum total cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum total cholesterol

  • Change in serum low-density lipoprotein (LDL) cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum calculated LDL cholesterol

  • Change in serum high-density lipoprotein (HDL) cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum HDL cholesterol

  • Change in serum triglycerides [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum triglycerides

  • Change in serum apolipoprotein B (apoB) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum apolipoprotein B

  • Change in serum c-reactive protein (CRP) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum c-reactive protein

  • Change in serum orosomucoid [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum orosomucoid

  • Change in serum haptoglobin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum haptoglobin

  • Change in serum alpha-1-antitrypsin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum alpha-1-antitrypsin

  • Change in serum aspartate aminotransferase (AST) [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Change from baseline in fasting serum aspartate aminotransferase

  • Change in serum alanine aminotransferase (ALT) [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Change from baseline in fasting serum alanine aminotransferase

  • Serum calcium [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Absolute concentration of serum calcium

  • Urinary calcium:creatinine ratio [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Urinary calcium:creatinine ratio


Estimated Enrollment: 160
Study Start Date: October 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
30g normal cheddar cheese once per week
Dietary Supplement: Control
Normal cheddar cheese
Experimental: Vitamin D
30g cheddar cheese containing 28,000IU vitamin D once per week
Dietary Supplement: Vitamin D
Vitamin D3 supplemented cheddar cheese
Other Name: Vitamin D3

Detailed Description:

Type 2 diabetes (T2D) is an increasingly prevalent and serious condition whose risk appears to be increased by low serum vitamin D concentrations. Epidemiological studies show an association between increased diabetes risk and low serum vitamin D and studies suggest that vitamin D may protect against diabetes by reducing chronic inflammation and improving insulin sensitivity and insulin secretion. Although clinical studies show some of these effects, no studies have been able to show that vitamin D supplementation reduces post-prandial blood glucose, the most clinically relevant marker of diabetes and dysglycemia. Previously, the investigators showed that cheddar cheese and low-fat cheese can be fortified with high levels of vitamin D3 (28,000IU/ 30g portion) and that, in this form, it is at least as a effective as vitamin D3 supplements in raising serum vitamin D concentrations. Since post-prandial glucose is most sensitive to changes in insulin sensitivity the main purpose of this study is to determine the effect of vitamin D supplementation on oral glucose tolerance (ie. serum glucose 2h after 75g oral glucose) in individuals who are at risk for developing T2D. Secondary objective are to determine the effect of vitamin D supplementation on insulin sensitivity, insulin secretion, inflammatory markers, blood lipids and markers of safety including serum parathyroid hormone levels and urinary calcium excretion.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male or non-pregnant, non-lactating females, aged 18-75
  • volunteered to participate by signing the consent form
  • BMI <40kg/ m2
  • vitamin D insufficient, defined as: serum 25(OH) vitamin D3 (25(OH)D) concentration ≤65nmol/ L
  • increased risk for diabetes, defined as: FINDRISC score >10 for Caucasians or >6 for non-Caucasians OR presence of metabolic syndrome
  • dysglycemia, defined as:fasting serum glucose 5.6 to 6.9 mmol/L, inclusive OR HbA1c 0.054 to 0.064, inclusive
  • systolic blood pressure ≤150/95 mmHg if not being treated for hypertension or ≤140/90 mmHg if on treatment for hypertension.
  • taking no prescription drugs, or stable (for at least 6 weeks) dose of birth control pill, or drug(s) used to treat hypertension, hyperlipidemia, depression or other mental illness or hypothyroid.
  • taking no supplements, or stable (for at least 6 weeks) dose of supplement(s).

Exclusion Criteria:

  • subjects not meeting all inclusion criteria
  • history of renal failure or liver disease
  • serum creatinine >1.8 times upper limit of normal (ULN)
  • serum aspartate or alanine transaminase (AST,ALT) >3 times ULN
  • current use of drug or drugs to treat diabetes or use of steroids or pancreatic enzymes
  • within 6 weeks of randomization, change in dose of supplements or drug(s) used to treat hypertension, hyperlipidemia, depression or other mental illness or hypothyroid.
  • use of antibiotics within 3 months.
  • medical or surgical event requiring hospitalization within 3 months of randomization
  • presence of any condition affecting nutrient absorption
  • intolerance to cheese
  • plan to travel outside Canada for more than 14 consecutive days during the trial
  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: NCT01726777

Contacts
Contact: Tracy S Moreira-Lucas, MSc 416-861-0506 ext 210 tracy.moreira@mail.utoronto.ca

Locations
Canada, Ontario
University of Guelph Recruiting
Guelph, Ontario, Canada, N1G 2W1
Contact: Alison M Duncan, R.D., Ph.D    519-824-4120 ext 53416    amduncan@uoguelph.ca   
Principal Investigator: Alison M Duncan, R.D., PhD         
Glycemic Index Laboratories Recruiting
Toronto, Ontario, Canada, M5C 2N8
Contact: Tracy Moreira-Lucas, MSc    416-861-0506 ext 210    tracy.moreira@mail.utoronto.ca   
Principal Investigator: Thomas MS Wolever, PhD, DM         
Canada, Quebec
Institut de recherches cliniques de Montréal Recruiting
Montreal, Quebec, Canada, H2W 1R7
Contact: Diane Mignault       diane.mignault@ircm.qc.ca   
Principal Investigator: Remi Rebasa-Lhoret, MD         
Sponsors and Collaborators
University of Toronto
Dairy Farmers of Canada
Public Health Agency of Canada (PHAC)
Investigators
Principal Investigator: Thomas MS Wolever, DM, PhD University of Toronto
  More Information

No publications provided

Responsible Party: Thomas Wolever, Professor, University of Toronto
ClinicalTrials.gov Identifier: NCT01726777     History of Changes
Other Study ID Numbers: UTRS-27546
Study First Received: November 9, 2012
Last Updated: April 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of Toronto:
Randomized controlled clinical trial
Diabetes
Vitamin D
Oral glucose tolerance
Blood glucose
Insulin resistance

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

ClinicalTrials.gov processed this record on September 18, 2014