Effect of Vitamin D3 Supplementation on Insulin Resistance- The DIR Study

Insulin Resistance Clinical Trial

Official title:

Effect of Vitamin D3 Supplementation on Insulin Resistance and Cardiovascular Risk Factors in People at High Risk of Type 2 Diabetes and Cardiovascular Disease (The DIR Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01889810
• Other study ID #: QUB: B12/35; HSC: 12117MMcK-AS
• Status: Completed
• Phase: N/A
• Start date: August 2013
• Est. completion date: June 2016

Study information

• Verified date: June 2022
• Source: Queen's University, Belfast
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Insulin resistance is a state where the body does not respond as it should to the insulin it produces. Individuals who are insulin resistant are at increased risk of both heart disease and type 2 diabetes; importantly, diabetes more than doubles the risk of heart disease, independent of other recognised risk factors. Interventions that prevent or reverse insulin resistance may help to attenuate risk of heart disease and diabetes. A number of randomised controlled trials provide proof of concept evidence regarding a beneficial effect of vitamin D on insulin resistance and other cardiovascular risk markers but experts have stated that further studies are required. Importantly, these studies should use appropriate endpoints, provide a high enough dose of vitamin D to optimise vitamin D status, and they should be conducted in clearly defined populations, The vitamin D trial we propose addresses these issues and aims to evaluate a potentially straightforward and low cost health care intervention for populations at highrisk of heart disease and diabetes. Specifically, this study would provide clinically relevant information on the metabolic effects of optimising vitamin D status in these high risk patients. This has clear economic and social implications given the current, and projected, burden of heart disease and diabetes. This study will investigate the effect of vitamin D3 supplementation on insulin resistance and cardiovascular risk factors in people at high risk of type 2 diabetes and cardiovascular disease using the gold standard euglycaemic hyperinsulinaemic clamp method.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Impaired glucose tolerance (Fasting glucose <7.0 mmol/L (126mg/dl) and 2hr post-glucose load 7.8-11.0 mmol/L (140-199 mg/dl) or Impaired fasting glucose 5.6-6.9 mmol/L (100-125mg/dL) defined according to American Diabetes Association
• Sub-optimal vitamin D status (<50nmol/L)

Exclusion Criteria:

• Diabetes mellitus
• Established cardiovascular disease
• Psychiatric problems
• Pregnant or lactating
• Medical conditions or dietary restrictions that would substantially limit ability to complete the study requirements
• Excessive alcohol consumption (>28 Units/week men or >21 Units/week women)
• Already taking vitamin D supplements > 10 µg/d
• Medical conditions or medications that could influence vitamin D metabolism
• History of kidney stones
• Hypercalcaemia
• Hyperparathyroidism
• Significant liver and renal disease (liver function tests >3x upper limit of normal and glomerular filtration rate <30ml/min)

Related Conditions & MeSH terms

• Glucose Intolerance
• Insulin Resistance
• Pre-diabetes
• Prediabetic State
• Sub-optimal Vitamin D Status

Intervention

Dietary Supplement:
• Vitamin D3 supplementation
3000IU (75µg) vitamin D3 will be given daily for a period of 26 weeks to the group who receive the active comparator. The efficacy of vitamin D3 supplementation on insulin resistance will be compared to the placebo group.

Locations

Country	Name	City	State
United Kingdom	Queen's University, Belfast	Belfast	N. Ireland

Sponsors (4)

Lead Sponsor	Collaborator
Queen's University, Belfast	HSC Research & Development Division, Public Health Agency, Northern Ireland, Northern Ireland Chest Heart and Stroke, The Metabolic Unit Research Fund, The Royal Hospitals, Belfast, Northern Ireland

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Wallace HJ, Holmes L, Ennis CN, Cardwell CR, Woodside JV, Young IS, Bell PM, Hunter SJ, McKinley MC. Effect of vitamin D3 supplementation on insulin resistance and beta-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2019 Nov 1;110(5):1138-1147. doi: 10.1093/ajcn/nqz171. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Insulin Resistance	Insulin resistance will be measured using the gold standard euglycaemic-hyperinsulinaemic clamp method (note - it is anticipated that a total of 60 volunteers will complete the primary endpoint assessment).	Measured at baseline and after 6 months
Secondary	Change in Vitamin D Status	Change in vitamin D status will be measured using the gold standard Ultra performance liquid chromatography followed by tandem mass spectrometry	Measured at baseline and after 6 months
Secondary	Change in Markers of Cardiovascular Risk	Measurements of seated and 24-hour ambulatory blood pressure, lipids, homeostasis model assessment (HOMA), HbA1c, and inflammatory and immune function markers including tumour necrosis factor-alpha and high sensitivity c-reactive protein	Measured at baseline and after 6 months
Secondary	Change in Carotid-femoral Pulse Wave Velocity (PWV)	Assessed by sequential tonometry with ECG gating using the SphygmoCor PWV System	Measured at baseline and after 6 months
Secondary	Change in Hand Grip Strength	Assessed using hand held dynamometer	Measured at baseline and after 6 months
Secondary	Health Status	SF-36 Questionnaire	Measured at baseline and after 6 months