Vitamin D Treatment, Pharmacogenetics and Glucose Metabolism

NCT ID: NCT01721915

Last Updated: 2018-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2017-10-12

Brief Summary

Background: Polycystic ovary syndrome (PCOS) is as common as 5-10% of all women in Austria. PCOS women frequently present with metabolic disturbances, hyperandrogenism and infertility. New therapy concepts are warranted. In our recent pilot study, vitamin D (vitD) supplementation significantly improved glucose metabolism and fertility. However, the efficacy of vitD administration shows individual variability indicating endogenous influences on pharmacological effects.

A recent genome-wide association study reported three loci (DHCR7, CYP2R1, and GC) associated with vitD insufficiency. Moreover, vitD receptor (VDR) gene variants have already been known to be associated with insulin resistance.

Aim: To test the hypothesis that vitD is efficient in changing metabolic parameters in PCOS and non-PCOS women longitudinally and to generate data on pharmacogenetic effects of vitD related genetic determinants adjusted for environmental factors.

Primary outcome: Change from baseline in AUCgluc after vitD treatment. Secondary outcome: To generate the hypothesis that changes in metabolic and endocrine parameters following vitD treatment are associated with vitD related gene variants.

Methods: 150 PCOS women with 25-hydroxyvitamin D (cholecalciferol, [25(OH)D]) levels <30 ng/ml will be treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled trial over 24 weeks and investigated for metabolic and endocrine parameters as well as vitD related genetic variants. In addition, 150 non-PCOS women with 25(OH)D <30 ng/ml will be treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled trial over 24 weeks and investigated for metabolic and endocrine parameters as well as vitD related genetic variants. The response to vitD supplementation in both groups will be analysed according to genotype profiles.

Significance: VitD might be a new therapeutic option without major side effects for PCOS patients. Exploring specific loci for pharmacogenetic vitD actions would open a new window for therapy modulation in PCOS and other metabolic diseases.

Conditions

Polycystic Ovary Syndrome; Healthy; Vitamin D Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vitamin D supplementation

The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)

Group Type: EXPERIMENTAL

Vitamin D supplementation

Intervention Type: DRUG

The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)

Placebo

the placebo group will receive oily drops without vitD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Vitamin D supplementation

The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

A11CC05 Colecalciferol

Eligibility Criteria

Inclusion Criteria

PCOS women:

• 25(OH)D levels below 30 ng/ml (measured at the baseline visit)
• Polycystic ovary syndrome defined by the Androgen Excess Society (AES) criteria
• Female, age of ≥ 18 and <45 years
• BMI status: 75 PCOS women with BMI ≤25 kg/m² and 75 PCOS women with BMI>25 kg/m²
• Written informed consent before study entry

Control women:

• 25(OH)D levels below 30 ng/ml (measured at the baseline visit)
• Female, age of ≥ 18 and <45 years
• BMI status: 75 nonPCOS women with BMI ≤25 kg/m² and 75 nonPCOS women with BMI>25 kg/m²
• Written informed consent before study entry

Exclusion Criteria

PCOS women:

• Hypercalcemia defined as a serum calcium > 2,7 mmol/L
• Pregnancy or lactating women
• Disorders associated with androgen excess and/or menstrual irregularities apart from PCOS (thyroid dysfunction, hyperprolactinemia, adrenal hyperplasia, androgen secreting tumors)
• Prevalent type 2 diabetes
• Regular intake of vitD supplements at any time before study entry
• Intake of medication influencing metabolic or endocrine parameters (insulin sensitizers, oral contraceptives, …) in the last 3 months before study entry

Control women:

• Hypercalcemia defined as a serum calcium > 2,7 mmol/L
• Established PCOS or any of the AES criteria 29 (hyperandrogenism (clinical and/or biochemical), oligo- or anovulation, or polycystic ovaries on ultrasound)
• Disorders associated with androgen excess and/or menstrual irregularities apart from PCOS (thyroid dysfunction, hyperprolactinemia, adrenal hyperplasia, androgen secreting tumors)
• Prevalent type 2 diabetes
• Pregnancy or lactating women
• Regular intake of vitD supplements at any time before study entry
• Intake of medication influencing metabolic or endocrine parameters (insulin sensitizers, oral contraceptives, …) in the last 3 months before study entry

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Austrian Science Fund (FWF)

OTHER

Sponsor Role: collaborator

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Lerchbaum Elisabeth, MD

A randomized, double-blind, placebo controlled trial to evaluate the effects of vitamin D

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elisabeth Lerchbaum, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Graz

Locations

Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Metabolism

Graz, , Austria

Countries

Austria

Other Identifiers

KLI 274

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

VitDPCOS1.0

Identifier Type: -

Identifier Source: org_study_id