Vitamin D Replacement in Insulin Resistant South Asians

NCT01385345 | Terminated DMC

• 1 other identifier: 0166
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the hypothesis that 6 months of periodic high dose Vitamin D3 replacement (200,000 and 100,000 units cholecalciferol, oral liquid drops at 6 to 8 week intervals) followed in-between by daily 1000 units, decreases insulin resistance by HOMA2-IR ≥ 0.36, in comparison to control, standard dose Vitamin D3 1000IU/ day for 6 months, in south Asians with both Vitamin D deficiency (defined as 25 Hydroxy vitamin D \< 25nmol/l) and insulin resistance (defined as HOMA1 -IR≥ 1.93). The hypothesis formed suggests that insulin resistance developed in South Asians is explained, at least in part, by the presence of Vitamin D Deficiency (VDD). Therefore if the VDD is reversed/ 'normalised into target range' using Vitamin D therapy in individuals at risk of diabetes, then markers of insulin resistance should reduce from baseline values. However, current UK recommended doses of Vitamin D do not adequately replenish severe VDD, common in South Asians, back into the target range and therefore will not reduce insulin resistance markers. Therefore only higher pharmacological doses are able to replace severe Vitamin D deficiency adequately and improve insulin resistance markers.

Conditions

Vitamin D Deficiency; Insulin Resistance

Keywords

Vitamin D deficiency; Insulin resistance

Outcome Measures

Primary Outcomes (1)

• HOMA2-IR (homeostatic model assessment of insulin resistance)

  This study will test the hypothesis that 6 months of periodic high dose Vitamin D3 replacement (200,000 and 100,000 units cholecalciferol, oral liquid drops at 6 to 8 week intervals) followed in-between by daily 1000 units, decreases insulin resistance by HOMA2-IR ≥ 0.36, in comparison to control, standard dose Vitamin D3 1000IU/ day for 6 months, in south Asians with both Vitamin D deficiency (defined as 25 Hydroxy vitamin D \< 25nmol/l) and insulin resistance (defined as HOMA1 -IR≥ 1.93).

  6 months

Secondary Outcomes (4)

• fasting plasma glucose

  6 months

• HbA1c

  6 months

• two hour plasma glucose

  6 months

• Tolerability of high dose Vitamin D3 treatment regime

  6 months

Study Arms (2)

Vitamin D3 high dose

ACTIVE COMPARATOR

200,000 units (time 0) followed by (100,000 units) at months 1.5, 3 and 5. Participants will also have daily 1,000 units per day to mirror the control arm and maintain double blinding.

Drug: Vitamin D3 cholecalciferol

Vitamin D3

PLACEBO COMPARATOR

Participants will have a placebo liquid (to mirror the active arm high dose Vitamin D3) and also have daily 1,000 units Vitamin D3.

Drug: Vitamin D3 cholecalciferol

Interventions

Vitamin D3 cholecalciferol DRUG

High dose Vitamin D3 (200,000 units followed by 100,000 units x 3 over 6 months) plus daily 1,000 units Vitamin D3 per day vs only daily 1,000 units Vitamin D3 per day

Vitamin D3; Vitamin D3 high dose

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• We will include the following people if they meet all criteria:
• year old south Asian (Bangladeshi, Indian or Pakistani) men or women.
• A low vitamin D level (defined by a specific marker, 25(OH)VitD \<25 nmol/L)
• Insulin resistance, defined as homeostatic model assessment of Insulin resistance (HOMA1-IR) ≥ 1.93.

You may not qualify if:

• We will exclude people if they have any one of the following:
• Those who have been told by a doctor they have diabetes (Type 1 or 2).
• Those who developed new diabetes (World Health Organisation (WHO) 1999 guidelines) detected on the Screening Visit fasting glucose test (such participants will be offered a confirmatory test to determine if they have diabetes with an oral glucose tolerance test) or the oral glucose tolerance test at Baseline Visit. Any individual with new diabetes will have follow up arranged with a doctor. If the confirmatory test does not show new diabetes, the participant will is eligible to re-enter the study.
• HbA1c ≥ 7.0% which is suggestive of diabetes.
• Pre-existing calcium and/or Vitamin D tablets (D2 ergocalciferol or D3 cholecalciferol) / therapy (e.g. intramuscular injections, oral liquid preparations) or previous adverse reaction to Vitamin D (D2 or D3). Any individual who has previously been on these therapy must have been off Vitamin D/ Calcium for at least six months.
• Pregnancy or breast feeding females, or actively trying/ intending to become pregnant during the planned six month trial.
• A history of known or newly detected hypercalcaemia or hypocalcaemia, hyperparathyroidism (that induce high calcium levels), kidney stones or other kidney problems/ low kidney function (estimated glomerular filtration rate \<60 = Chronic kidney disease stage 3, 4 or 5) or known history of liver problems/ disorders.
• A history of known bone diseases (e.g. osteoporosis, osteomalacia, osteopetrosis) or muscle diseases.
• Any participant discovered to have new kidney/ liver/ bone or other health problems discovered during Screening or Baseline visit. Such individuals will have appropriate follow up organised. A raised Parathyroid Hormone (PTH) will be considered in the clinical context of symptoms, Alkaline Phosphatase (ALP) and Vitamin D level (i.e. may or may not be excluded).
• Terminal illness, malignancy or physical inability to give consent (not language barriers).
• Taking medications which may interfere with Vitamin D metabolism (phenytoin, carbamazepine, primidone and barbiturates) or potentially leading to other problems (bendroflumethiazide, digoxin).
• Participants unable to commit time for the six month study (e.g. holiday abroad, work commitments).
• Actively taking part in another interventional study (e.g. medication, lifestyle Randomised controlled trials); observational and cross sectional studies are still permitted.

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

Leicester Diabetes Centre, University Hospitals of Leicester

Leicester, Leicestershire, LE5 4PW, United Kingdom

Location

MeSH Terms

Conditions

Vitamin D Deficiency; Insulin Resistance

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Melanie J Davies, MD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 30, 2011
• Study Start: August 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 30, 2020

Record last verified: 2013-01

Locations

GB (1)