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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Tan Tock Seng Hospital
Sponsor:
Collaborators:
Duke-NUS Graduate Medical School
National Healthcare Group, Singapore
Information provided by (Responsible Party):
Rinkoo Dalan, Tan Tock Seng Hospital
ClinicalTrials.gov Identifier:
NCT01741181
First received: November 30, 2012
Last updated: December 4, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus Type 2
Vitamin D Deficiency
Drug: Vitamin D supplementation
Drug: Placebo Pill
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Tan Tock Seng Hospital:

Primary Outcome Measures:
  • Endothelial function as assessed by the reactive hyperemia index and endothelial progenitor cells [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Markers of endothelial cell activation and thrombogenesis [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Biomarkers measured include hsCRP, e-selectin,von-willebrand factor(vWF)

  • No. of circulating endothelial cells and endothelial microparticles [ Time Frame: 16-20 weeks ] [ Designated as safety issue: No ]
    The no. of circulating endothelial cells and endothelial microparticles will be estimated before and after intervention.


Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vitamin D supplementation
Vitamin D3 tablets (cholecalciferol)
Drug: Vitamin D supplementation
Vitamin D3 marketed by oneNine57
Other Name: Vitamin D3-Cholecalciferol 1000units per tablet.
Placebo Comparator: Placebo pill
Placebo pill
Drug: Placebo Pill
Placebo pill supplied by oneNine 57 imported to Singapore with approval and import licence from HSA.
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01741181

Contacts
Contact: Rinkoo Dalan, MBBS,FRCP 81263176 rinkoo_dalan@ttsh.com.sg

Locations
Singapore
Tan Tock Seng Hospital Recruiting
Singapore, Singapore, 308433
Contact: Rinkoo Dalan, MBBS,FRCP    65-81263176    rinkoo_dalan@ttsh.com.sg   
Principal Investigator: Rinkoo Dalan, MBBS,FRCP         
Sponsors and Collaborators
Tan Tock Seng Hospital
Duke-NUS Graduate Medical School
National Healthcare Group, Singapore
Investigators
Principal Investigator: Rinkoo Dalan, MBBS, FRCP Tan Tock Seng Hospital
  More Information

No publications provided

Responsible Party: Rinkoo Dalan, Consultant, Tan Tock Seng Hospital
ClinicalTrials.gov Identifier: NCT01741181     History of Changes
Other Study ID Numbers: DIMENSION-03
Study First Received: November 30, 2012
Last Updated: December 4, 2012
Health Authority: Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority
Singapore: Institutional Review Board
Singapore: Singapore Clinical Research Institute

Keywords provided by Tan Tock Seng Hospital:
25(OH)Vitamin D
Diabetes mellitus
Endothelial Function

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Vitamin D Deficiency
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 20, 2014