Vitamin D Treatment, Pharmacogenetics and Glucose Metabolism

NCT01721915 | Completed Phase 4

• 2 other identifiers: VitDPCOS1.0KLI 274
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

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

Keywords

Polycystic Ovary Syndrome (PCOS); glucose metabolism; Vitamin D deficiency; vitamin D supplementation; pharmakogenetics; women

Outcome Measures

Primary Outcomes (1)

• Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc

  Change from Baseline in AUC gluc at 24 weeks

Secondary Outcomes (8)

• Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR)

  Change from Baseline in insulin resistance at 24 weeks

• Lipid levels (total cholesterol)

  Change from Baseline in total cholesterol at 24 weeks

• HbA1c

  Change from Baseline in HbA1c at 24 weeks

• Testosterone

  Change from Baseline in testosterone at 24 weeks

• Menstrual frequency

  Change from Baseline in menstrual frequency at 24 weeks

Study Arms (2)

Vitamin D supplementation

EXPERIMENTAL

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)

Drug: Vitamin D supplementation

Placebo

PLACEBO COMPARATOR

the placebo group will receive oily drops without vitD

Drug: Placebo

Interventions

Vitamin D supplementation 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)

Also known as: A11CC05 Colecalciferol

Vitamin D supplementation

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• PCOS women:
• (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:
• (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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Graz: lead
• Austrian Science Fund (FWF): collaborator

Study Sites (1)

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

Graz, 8036, Austria

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Vitamin D Deficiency

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Elisabeth Lerchbaum, MD

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A randomized, double-blind, placebo controlled trial to evaluate the effects of vitamin D

Study Record Dates

• First Submitted: October 31, 2012
• First Posted: November 6, 2012
• Study Start: October 1, 2012
• Primary Completion: October 12, 2017
• Study Completion: October 12, 2017
• Last Updated: March 20, 2018

Record last verified: 2018-03

Locations

AU (1)