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Completed

NCT Number: NCT02112721

Can Vitamin D Supplementation Prevent Type 2 Diabetes?

The aim of this study is to determine whether vitamin D supplementation in overweight/obese individuals with vitamin D deficiency can improve insulin secretion and/or insulin resistance by decreasing subclinical inflammation.

Results of the present study may help to identify new strategies to prevent type 2 diabetes in high-risk groups (i.e. overweight and obese individuals, and individuals with a strong family history of diabetes).

Hypothesis: That increasing plasma 25(OH)D concentrations in healthy individuals at risk for type 2 diabetes with low vitamin D levels through vitamin D supplementation, will improve insulin sensitivity and also insulin secretion by reducing the underlying sub-clinical chronic inflammation.

Aims: To establish whether 16-week vitamin D supplementation given to healthy individuals with low vitamin D levels will:

1. improve insulin sensitivity (in vivo and tissue) and/or insulin secretory function 2. determine whether this relationship is mediated by a reduced chronic inflammation

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Key information

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Monash Centre for Health Research and Implementation

Melbourne, Victoria, 3168, Australia

About this study

Numerous studies documented that low vitamin D levels are a serious health risk. Despite the sunny climate in Australia, low vitamin D status is becoming increasingly prevalent and people with vitamin deficiency represent more than 30% of the healthy Australian population. Although sun exposure can maintain good vitamin D levels, often sun exposure is limited as people work long hours indoors, and use sunscreen or protective clothing to reduce skin cancer risk when outdoors. Moreover, it is difficult to obtain sufficient vitamin D from food alone; few foods are naturally rich in vitamin D and in Australia, few foods are fortified.

While the importance of vitamin D for bone mineralization is well known, it is less clear how vitamin D protects against type 2 diabetes and cardiovascular disease. Every day in Australia around 275 adults develop diabetes and its prevalence continues to rise.

We are therefore arguing for a well-designed intervention trial to define the preventive potential and physiological mechanisms of the effects of vitamin D supplementation. In addition, we plan to explore the mechanisms underlying the relationship between vitamin D deficiency and the risk for type 2 diabetes, via its influence on chronic inflammation. Our clinical trial will focus on healthy adults with low vitamin D status and will examine the effects on insulin sensitivity and secretion measured by 'gold standard' methodology when vitamin D is restored to optimum levels. It is in particularly important to determine whether vitamin D affects both or only one of these defects because there is evidence from observational studies that there is a relationship between vitamin D levels and both insulin sensitivity and secretion.

The proposed intervention study will potentially supply important evidence on how restoring vitamin D levels may protect against type 2 diabetes. Such findings could have direct relevance for novel approaches to diabetes prevention.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age >18 or <60 years,
  • 25(OH)D < 50 nmol/L
  • Weight change < 5 kg in last 12 months
  • BMI >25kg/m2 but weight <159kg due to DEXA scan restrictions
  • Non-diabetic, no allergy, non-smoker, no high alcohol use
  • No current intake of medications including vitamin supplements
  • No kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine or central nervous system disease, as well as no psychiatric disorders, no active cancer within the last five years; no presence of acute inflammation (by history, physical or laboratory examination)
  • Not menopausal, pregnanct or lactating

Exclusion criteria

  • Age <18 or > 60 years
  • 25(OH)D > 50 nmol/L
  • Weight change > 5 kg in last 12 months
  • Diabetes (diagnosed or oral glucose tolerance test (OGTT), hypercalcaemia, allergy
  • Current smoking habit, high alcohol use
  • Current intake of medications including vitamin supplements
  • Kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine or central nervous system disease, as well as psychiatric disorder, active cancer within the last five years; presence of acute inflammation (by history, physical or laboratory examination)
  • Menopause, pregnancy or lactation

Treatment and study plan

Vitamin D

Dietary Supplement

Other names: Ostellin

Placebo

Dietary Supplement

Primary outcomes

  1. Initial Insulin Sensitivity Measure using Euglycaemic glucose clamp

    Time frame: Week 1

    The clamp will be used to measure insulin sensitivity. The clamp is initiated by an intravenous bolus injection of insulin (9milliUnit/kg). Insulin is then constantly infused at a rate of 40 milliUnit.m-2.min-1 for 120 min into an arm vein, whilst glucose is variably infused to maintain euglycaemia. Plasma glucose values will be monitored every 5 minutes during the clamp and the variable infusion rate of glucose is adjusted to maintain blood glucose at a constant value of 5mmol/L.

  2. Follow up Insulin Sensitivity Measure using Euglycaemic glucose clamp

    Time frame: Week 17

    The clamp will be used to measure insulin sensitivity. The clamp is initiated by an intravenous bolus injection of insulin (9milliUnit/kg). Insulin is then constantly infused at a rate of 40 milliUnit.m-2.min-1 for 120 min into an arm vein, whilst glucose is variably infused to maintain euglycaemia. Plasma glucose values will be monitored every 5 minutes during the clamp and the variable infusion rate of glucose is adjusted to maintain blood glucose at a constant value of 5mmol/L.

Secondary outcomes

  1. Initial measurement of inflammatory markers

    Time frame: Week 1

    Plasma inflammatory markers (interleukin 1β, 6, 8 and 10, TNFα, macrophage migration inhibitory factor, monocyte chemotactic protein-1) will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA) (interassay Coefficients of Variation: 7.2%, 10.2%, 5.8%, respectively). Plasma C- reactive protein (hsCRP) via a high sensitivity assay (BN-II nephelometer; Dade Behring Diagnostics, NSW).

  2. Follow Up Measurement of inflammatory markers

    Time frame: Week 17

    Plasma inflammatory markers (interleukin 1β, 6, 8 and 10, TNFα, macrophage migration inhibitory factor, monocyte chemotactic protein-1) will be measured by quantitative sandwich enzyme immunoassays (R & D Systems Inc, USA) (interassay Coefficients of Variation: 7.2%, 10.2%, 5.8%, respectively). Plasma C- reactive protein (hsCRP) via a high sensitivity assay (BN-II nephelometer; Dade Behring Diagnostics, NSW).

  3. Initial Measure of Adiposity (DEXA)

    Time frame: Week 1

    body composition by dual energy x-ray absorptiometry (DEXA), which is a non-invasive assessment of soft tissue composition by region with a precision of 4-5%; central adiposity assessed in duplicate using a constant-tension tape for taking waist, and hip circumference. Bioimpedance measurement will be also collected for validation purposes.

  4. Follow Up Measure of Adiposity (DEXA)

    Time frame: Week 17

    body composition by dual energy x-ray absorptiometry (DEXA), which is a non-invasive assessment of soft tissue composition by region with a precision of 4-5%; central adiposity assessed in duplicate using a constant-tension tape for taking waist, and hip circumference. Bioimpedance measurement will be also collected for validation purposes.

  5. Initial Oral Glucose Tolerance Test - OGTT

    Time frame: Week 1

    After a 10-12 h overnight fast, participants will ingest 75g of glucose over 2 mins. Blood samples will be drawn at 0, 30, 60, 90 and 120 min for plasma glucose and insulin concentrations. We will evaluate the area under the curve.

  6. Follow Up Oral Glucose Tolerance Test -OGTT

    Time frame: Week 17

    After a 10-12 h overnight fast, participants will ingest 75g of glucose over 2 mins. Blood samples will be drawn at 0, 30, 60, 90 and 120 min for plasma glucose and insulin concentrations. We will evaluate the area under the curve.

  7. Initial Acute Insulin Secretory Response - Intravenous Glucose Tolerance Test

    Time frame: Week 1

    This will be measured in response to 25g intravenous glucose and calculated as the average incremental plasma insulin level from the third to the fifth minute after the glucose bolus.

  8. Follow up Acute Insulin Secretory Response- Intravenous Glucose Tolerance Test

    Time frame: Week 17

    This will be measured in response to 25g intravenous glucose and calculated as the average incremental plasma insulin level from the third to the fifth minute after the glucose bolus.

Other outcomes

  1. Initial - Other Tissue Analyses

    Time frame: Week 1

    We will measure changes in the expression and activation of important insulin signalling proteins, including the insulin receptor,and we will measure inflammation markers in skeletal, muscle and adipose tissue.

  2. Follow Up- Other Tissue Analyses

    Time frame: Week 17

    We will measure changes in the expression and activation of important insulin signalling proteins, including the insulin receptor,and we will measure inflammation markers in skeletal, muscle and adipose tissue.

  3. Resting systolic and diastolic blood pressure

    Time frame: Week 1

    Resting systolic and diastolic blood pressure and pulse rate will be measured using an automated oscillometric measurement system (Dinamap, USA) after a 30 minute rest.

  4. Follow up Resting systolic and diastolic blood pressure

    Time frame: Week 17

    Resting systolic and diastolic blood pressure and pulse rate will be measured using an automated oscillometric measurement system (Dinamap, USA) after a 30 minute rest.

  5. Initial Arterial waveform measurement

    Time frame: Week 1

    This is done with the BP+ device (Uscom, Australia). This is a device for non-invasive measurement of central blood pressure and augmentation index using an oscillometric method.

  6. Follow up Arterial waveform measurement

    Time frame: Week 17

    This is done with the BP+ device (Uscom, Australia). This is a device for non-invasive measurement of central blood pressure and augmentation index using an oscillometric method.

  7. Initial Beck Depression Inventory

    Time frame: Week 1

    The Beck Depression Inventory (BDI), created by Dr. Aaron T. Beck, is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. It is designed for individuals aged 13 and over, and is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex.

  8. Follow Up Beck Depression Inventory

    Time frame: Week 17

    The Beck Depression Inventory (BDI), created by Dr. Aaron T. Beck, is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. It is designed for individuals aged 13 and over, and is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex.

  9. Initial Pain Impact Questionnaire (PIQ-6 questionnaire)

    Time frame: Week 1

    PIQ-6 measures the severity of pain and its impact on work and leisure activities, as well as on emotional well-being within a variety of diseases and general populations. This survey is intended for adults 18 years of age and older.

  10. Follow Up Pain Impact Questionnaire (PIQ-6 questionnaire)

    Time frame: Week 17

    PIQ-6 measures the severity of pain and its impact on work and leisure activities, as well as on emotional well-being within a variety of diseases and general populations. This survey is intended for adults 18 years of age and older.

Sponsors and collaborators

Lead sponsor

Monash University

Other

Collaborators

  • University of Auckland, New Zealand
  • University of Victoria

Registry information

Official study title

Can Vitamin D Supplementation Prevent Type 2 Diabetes by Improving Insulin Sensitivity and Secretion in Overweight Humans?

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Apr 14, 2014
Registry last updated
Dec 8, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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