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

Primary Purpose

Type 2 Diabetes Mellitus, Vitamin D Deficiency

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Control
Vitamin D
Sponsored by
University of Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Randomized controlled clinical trial, Diabetes, Vitamin D, Oral glucose tolerance, Blood glucose, Insulin resistance

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Guelph
  • Glycemic Index Laboratories
  • Institut de recherches cliniques de Montréal

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Control

Vitamin D

Arm Description

30g normal cheddar cheese once per week

30g cheddar cheese containing 28,000IU vitamin D once per week

Outcomes

Primary Outcome Measures

Change in plasma glucose concentration 2 hours after consuming 75g oral glucose (2 hour PC glucose, or 2hrPC glucose)
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)
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
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)
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
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
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)
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
Change from baseline in fasting plasma glucose
Change in glucose area under the curve
Change from baseline in incremental area under the glucose response curve after 75g oral glucose
Change in glycated hemoglobin
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
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.

Full Information

First Posted
November 9, 2012
Last Updated
September 15, 2015
Sponsor
University of Toronto
Collaborators
Dairy Farmers of Canada, Public Health Agency of Canada (PHAC)
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1. Study Identification

Unique Protocol Identification Number
NCT01726777
Brief Title
Effect of Vitamin D Supplementation on Glucose Tolerance in Subjects at Risk for Diabetes With Low Vitamin D.
Acronym
EVIDENCE
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.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Toronto
Collaborators
Dairy Farmers of Canada, Public Health Agency of Canada (PHAC)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus, Vitamin D Deficiency
Keywords
Randomized controlled clinical trial, Diabetes, Vitamin D, Oral glucose tolerance, Blood glucose, Insulin resistance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
30g normal cheddar cheese once per week
Arm Title
Vitamin D
Arm Type
Experimental
Arm Description
30g cheddar cheese containing 28,000IU vitamin D once per week
Intervention Type
Dietary Supplement
Intervention Name(s)
Control
Intervention Description
Normal cheddar cheese
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D
Other Intervention Name(s)
Vitamin D3
Intervention Description
Vitamin D3 supplemented cheddar cheese
Primary Outcome Measure Information:
Title
Change in plasma glucose concentration 2 hours after consuming 75g oral glucose (2 hour PC glucose, or 2hrPC glucose)
Description
Change from baseline in plasma glucose concentration 2 hours after consuming 75g oral glucose.
Time Frame
24 Weeks
Secondary Outcome Measure Information:
Title
Change in insulin resistance assessed using the homeostasis model assessment of insulin resistance (HOMA-IR)
Description
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).
Time Frame
24 weeks
Title
Change in Matsuda insulin sensitivity index
Description
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]).
Time Frame
24 weeks
Title
Change in insulin secretion assessed using the homeostasis model assessment of beta-cell function (HOMA-B)
Description
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).
Time Frame
24 weeks
Title
Change in insulinogenic index
Description
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.
Time Frame
24 weeks
Title
Change in disposition index derived from HOMA-IR and HOMA-B
Description
Change from baseline in disposition index which is HOMA-B/HOMA-IR, which have been defined above.
Time Frame
24 weeks
Title
Change in disposition index based on oral glucose tolerance test (OGTT)
Description
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.
Time Frame
24 weeks
Title
Change in fasting plasma glucose
Description
Change from baseline in fasting plasma glucose
Time Frame
24 weeks
Title
Change in glucose area under the curve
Description
Change from baseline in incremental area under the glucose response curve after 75g oral glucose
Time Frame
24 weeks
Title
Change in glycated hemoglobin
Description
Change from baseline in glycated hemoglobin (HbA1c)
Time Frame
24 weeks
Title
Correlation between changes in serum 25-hydroxy-vitamin D concentration (25(OH)D) and changes in 2 hour PC glucose
Description
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.
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Fasting serum 25(OH)D
Description
Absolute concentration of serum 25-hydroxy-vitamin D3
Time Frame
24 weeks
Title
Change in serum 25(OH)D
Description
Change from baseline in serum 25-hydroxy-vitamin D3
Time Frame
24 weeks
Title
Change in serum total cholesterol
Description
Change from baseline in fasting serum total cholesterol
Time Frame
24 weeks
Title
Change in serum low-density lipoprotein (LDL) cholesterol
Description
Change from baseline in fasting serum calculated LDL cholesterol
Time Frame
24 weeks
Title
Change in serum high-density lipoprotein (HDL) cholesterol
Description
Change from baseline in fasting serum HDL cholesterol
Time Frame
24 weeks
Title
Change in serum triglycerides
Description
Change from baseline in fasting serum triglycerides
Time Frame
24 weeks
Title
Change in serum apolipoprotein B (apoB)
Description
Change from baseline in fasting serum apolipoprotein B
Time Frame
24 weeks
Title
Change in serum c-reactive protein (CRP)
Description
Change from baseline in fasting serum c-reactive protein
Time Frame
24 weeks
Title
Change in serum orosomucoid
Description
Change from baseline in fasting serum orosomucoid
Time Frame
24 weeks
Title
Change in serum haptoglobin
Description
Change from baseline in fasting serum haptoglobin
Time Frame
24 weeks
Title
Change in serum alpha-1-antitrypsin
Description
Change from baseline in fasting serum alpha-1-antitrypsin
Time Frame
24 weeks
Title
Change in serum aspartate aminotransferase (AST)
Description
Change from baseline in fasting serum aspartate aminotransferase
Time Frame
24 weeks
Title
Change in serum alanine aminotransferase (ALT)
Description
Change from baseline in fasting serum alanine aminotransferase
Time Frame
24 weeks
Title
Serum calcium
Description
Absolute concentration of serum calcium
Time Frame
24 weeks
Title
Urinary calcium:creatinine ratio
Description
Urinary calcium:creatinine ratio
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas MS Wolever, DM, PhD
Organizational Affiliation
University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Guelph
City
Guelph
State/Province
Ontario
ZIP/Postal Code
N1G 2W1
Country
Canada
Facility Name
Glycemic Index Laboratories
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5C 2N8
Country
Canada
Facility Name
Institut de recherches cliniques de Montréal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada

12. IPD Sharing Statement

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

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