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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

November 9, 2012
April 7, 2014
October 2012
December 2015   (final data collection date for primary outcome measure)
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.
Change in 2 hour PC glucose [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
Change from baseline in plasma glucose concentration 2 hours after consuming 75g oral glucose.
Complete list of historical versions of study NCT01726777 on ClinicalTrials.gov Archive Site
  • 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.
  • Change in 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 as 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 [ 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 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 AUC [ 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(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.
  • 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
  • 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 LDL cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change from baseline in fasting serum calculated LDL cholesterol
  • Change in serum 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 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 AST [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Change from baseline in fasting serum aspartate aminotransferase
  • Change in serum 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
 
Effect of Vitamin D Supplementation on Glucose Tolerance in Subjects at Risk for Diabetes With Low Vitamin D.
Effect of Vitamin D Supplementation on Oral Glucose Tolerance in Subjects Exhibiting Marginal Vitamin D Status and an Increased Risk of Developing Diabetes.

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Type 2 Diabetes Mellitus
  • Vitamin D Deficiency
  • Dietary Supplement: Control
    Normal cheddar cheese
  • Dietary Supplement: Vitamin D
    Vitamin D3 supplemented cheddar cheese
    Other Name: Vitamin D3
  • Placebo Comparator: Control
    30g normal cheddar cheese once per week
    Intervention: Dietary Supplement: Control
  • Experimental: Vitamin D
    30g cheddar cheese containing 28,000IU vitamin D once per week
    Intervention: Dietary Supplement: Vitamin D
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
December 2015
December 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact: Tracy S Moreira-Lucas, MSc 416-861-0506 ext 210 tracy.moreira@mail.utoronto.ca
Canada
 
NCT01726777
UTRS-27546
No
Thomas Wolever, University of Toronto
University of Toronto
  • Dairy Farmers of Canada
  • Public Health Agency of Canada (PHAC)
Principal Investigator: Thomas MS Wolever, DM, PhD University of Toronto
University of Toronto
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP