Vitamin D Supplementation in Patients With Diabetes Mellitus Type 2 (DIMENSION)

November 17, 2014 updated by: Rinkoo Dalan, Tan Tock Seng Hospital

Vitamin D Supplementation in Patients With Diabetes Mellitus Type 2 and Low 25(OH)D Concentrations: Does it Help to Improve Endothelial Function-The DIMENSION TRIAL

Background and Objectives :

The presence of vitamin D deficiency in patients with type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD). We aim to see whether supplementation of vitamin D in these patients helps to improve the endothelial function (EF) a surrogate marker of CVD risk.

Hypothesis: Vitamin D supplementation in patients with T2DM and low serum 25(OH) D concentrations (<30ng/ml) will improve EF as measured by the Endo-PAT machine by 0.4 units (30% improvement over baseline) and/or will result in a increase of EPCs (CD133+/KDR+) and CD45dim CD34+/KDR.

The investigators will test this hypothesis by comparing 2 groups of T2DM patients randomized to placebo or vitamin D3 for 16 weeks.

Methods:

This is a 16 weeks trial in which 120 T2DM patients will be screened with the aim to recruit 60 T2DM patients with vitamin D deficiency or insufficiency. Out of these 60 patients , 30 patients will be started on vitamin D supplementation and 30 patients will be given a matched placebo. Endothelial function (EF) will be checked before and after supplementation to see a change in EF.

Significance of Project:

If this study shows a significant improvement of EF, it would justify larger scale studies to show that vitamin D supplementation in patients with T2DM mitigates CVD risk and vitamin D supplementation in patients with T2DM and vitamin D deficiency to improve CVD risk.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Overall Aims: Type 2 Diabetes Mellitus (T2DM) is increasingly more prevalent in Singapore and is a high cardiovascular diseases (CVD) risk factor (1,2). The presence of low serum 25(OH)D concentrations (<30ng/ml) has also been classified as an independent predictor of CVD(3,4) and has been seen to be more prevalent in T2DM (5-7). We aim to see whether replacement with vitamin D in these patients helps to mitigate CVD risk. Since endothelial dysfunction is one of the earliest manifestations of CVD and is a very robust surrogate marker, we aim to measure the endothelial function (EF) before and after vitamin D supplementation to evaluate for beneficial impact on this endpoint.

Specific Aims: Although, there are some small scale studies done with a single high dose replacement of vitamin D2/D3, no studies have been done using regular daily supplementation with vitamin D3 and with measurement of EF using the Endo-PAT machine or measurement of endothelial progenitor cells (EPCs).We are doing this pilot study to see whether replacement with vitamin D results in an improvement of EF as measured using the Endo-PAT and estimation of EPCs and some biomarkers as independent established surrogate markers of CVD risk. The estimation of endothelial progenitor cells has been proposed as a surrogate marker of vascular dysfunction and is known to be reduced in patients with cardiovascular risk factors (8). The no. of circulating endothelial cells (CECs) and endothelial microparticles have been seen to be elevated in patients with cardiovascular risk factors and DM and has also been proposed as a effective surrogate marker. We aim to quantify the no. of endothelial progenitor cells (EPCs) staining positive for CD133+/KDR (kinase insert domain-containing receptor),CD34+/KDR and CD45dim CD34+/KDR , CECs (CD 146+/CD45- ) and EMPs derived from endothelial progenitors (CD45-/CD146+/CD34+/CD117+) and from mature endothelial cells (CD45-/CD146+/CD34+/CD117-).using flow cytometry.

Primary Hypothesis:

Vitamin D supplementation in patients with T2DM and low serum 25(OH) D concentrations (<30ng/ml) will improve EF as measured by the Endo-PAT machine by 0.4 units (30% improvement over baseline) and/or will result in a increase of EPCs (CD133+/KDR+) and CD45dim CD34+/KDR. The investigators will test this hypothesis by comparing 2 groups of T2DM patients randomized to placebo or vitamin D3 for 16 weeks.

Secondary Objectives:

To explore the prevalence of low serum 25(OH) D concentrations (<30ng/ml) in T2DM patients and evaluate the difference in the EF in the two groups. To see whether vitamin D supplementation helps to further improve other parameters such as biomarkers, blood pressure, BMI, urine albumin-to-creatinine ratio (ACR), lipid profile of T2DM patients.

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore, 308433
        • Tan Tock Seng Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects with Type 2 Diabetes Mellitus
  • HbA1c : 6.0-10.0%
  • Male of female aged 21-80 years
  • Stable Diabetes, blood pressure and hyperlipidemia medications (a 25% dose adjustment is allowed) in the last three months
  • Baseline serum 25(0H)D concentration <30ng/ml for randomisation

Exclusion Criteria:

  • Baseline serum 25(OH)D concentration >30ng/ml
  • Baseline HbA1c>10.1%
  • Baseline hypercalcemia (Ca>2.58 mmol/L)
  • Known case of Primary Hyperparathyroidism
  • Known to be on bisphosphonates
  • Known to be on Vitamin D supplementation of 1000 units daily or more in the last one year.
  • Chronic renal failure with eGFR<30ml/min
  • Known to have cirrhosis of the liver or transaminitis with ALT/AST >3X ULN
  • Patients with h/o sarcoidosis, renal calculi or any malignancy
  • Patients on current treatment for tuberculosis
  • Pregnancy and Lactation
  • Women of childbearing potential not taking effective contraceptive measures.
  • Patients on long term glucocorticoids or anti-retroviral drugs
  • Patients on orlistat or other over the counter preparations that claim to block fat absorption.
  • A change in the type of medications for hypertension, diabetes mellitus and hyperlipidemia in the last three months
  • Patients who have undergone any form of bariatric surgery
  • Patients known to have any malabsorption disorders
  • Patients known to have osteoporosis or of baseline BMD scan shows osteoporosis as T score <-2.5SD (for randomisation)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo pill
Drug: Placebo Pill
Placebo pill supplied by oneNine 57 imported to Singapore with approval and import licence from HSA.
Other Names:
  • Placebo
Active Comparator: Vitamin D supplementation
Vitamin D3 tablets (cholecalciferol)
Drug: Vitamin D supplementation
Vitamin D3 marketed by oneNine57
Other Names:
  • Vitamin D3-Cholecalciferol 1000units per tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial function as assessed by the reactive hyperemia index and endothelial progenitor cells
Time Frame: 16 weeks
Endothelial function will be tested by using the EndoPAT machine which measures the reactive hyperemia index and by estimating the no. of endothelial progenitor cells in the peripheral blood by flow cytometry.
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Markers of endothelial cell activation and thrombogenesis
Time Frame: 16 weeks
Biomarkers measured include hsCRP, e-selectin,von-willebrand factor(vWF)
16 weeks
No. of circulating endothelial cells and endothelial microparticles
Time Frame: 16-20 weeks
The no. of circulating endothelial cells and endothelial microparticles will be estimated before and after intervention.
16-20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tan Tock Seng Hospital

Collaborators

National Healthcare Group, Singapore
Duke-NUS Graduate Medical School

Investigators

  • Principal Investigator: Rinkoo Dalan, MBBS, FRCP, Tan Tock Seng Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

November 30, 2012

First Submitted That Met QC Criteria

November 30, 2012

First Posted (Estimate)

December 4, 2012

Study Record Updates

Last Update Posted (Estimate)

November 18, 2014

Last Update Submitted That Met QC Criteria

November 17, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DIMENSION-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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