Vitamin D Treatment, Pharmacogenetics and Glucose Metabolism

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Medical University of Graz
Sponsor:
Collaborator:
Austrian Science Fund (FWF)
Information provided by (Responsible Party):
Lerchbaum Elisabeth, MD, Medical University of Graz
ClinicalTrials.gov Identifier:
NCT01721915
First received: October 31, 2012
Last updated: May 26, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Polycystic Ovary Syndrome
Healthy
Vitamin D Deficiency
Drug: Vitamin D supplementation
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double‐Blind, Placebo Controlled Trial to Evaluate the Effects of Vitamin D Supplementation on Metabolic and Fertility Parameters in PCOS Women

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc [ Time Frame: Change from Baseline in AUC gluc at 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR) [ Time Frame: Change from Baseline in insulin resistance at 24 weeks ] [ Designated as safety issue: No ]
  • Lipid levels (total cholesterol) [ Time Frame: Change from Baseline in total cholesterol at 24 weeks ] [ Designated as safety issue: No ]
  • HbA1c [ Time Frame: Change from Baseline in HbA1c at 24 weeks ] [ Designated as safety issue: No ]
  • Testosterone [ Time Frame: Change from Baseline in testosterone at 24 weeks ] [ Designated as safety issue: No ]
  • Menstrual frequency [ Time Frame: Change from Baseline in menstrual frequency at 24 weeks ] [ Designated as safety issue: No ]
  • Insulin sensitivity assessed by Quantitative Insulin-sensitivity Check Index (QUICKI) [ Time Frame: Change from baseline in QUICKI at 24 weeks ] [ Designated as safety issue: No ]
  • Free testosterone (FT) [ Time Frame: Change from Baseline in FT at 4 weeks ] [ Designated as safety issue: No ]
  • Triglycerides [ Time Frame: Change from Baseline in triglycerides at 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: October 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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)
Drug: 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)
Other Name: A11CC05 Colecalciferol
Placebo Comparator: Placebo
the placebo group will receive oily drops without vitD
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 44 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  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: NCT01721915

Contacts
Contact: Elisabeth Lerchbaum, MD 0043-316-385-81144 elisabeth.lerchbaum@medunigraz.at

Locations
Austria
Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Metabolism Recruiting
Graz, Austria, 8036
Contact: Elisabeth Lerchbaum, MD    0043-316-385-81144    elisabeth.lerchbaum@medunigraz.at   
Principal Investigator: Elisabeth Lerchbaum, MD         
Sponsors and Collaborators
Medical University of Graz
Austrian Science Fund (FWF)
Investigators
Principal Investigator: Elisabeth Lerchbaum, MD Medical University of Graz
  More Information

No publications provided

Responsible Party: Lerchbaum Elisabeth, MD, A randomized, double‐blind, placebo controlled trial to evaluate the effects of vitamin D, Medical University of Graz
ClinicalTrials.gov Identifier: NCT01721915     History of Changes
Other Study ID Numbers: VitDPCOS1.0, KLI 274
Study First Received: October 31, 2012
Last Updated: May 26, 2014
Health Authority: Austria: Federal Office for Safety in Health Care

Keywords provided by Medical University of Graz:
Polycystic Ovary Syndrome (PCOS)
glucose metabolism
Vitamin D deficiency
vitamin D supplementation
pharmakogenetics
women

Additional relevant MeSH terms:
Vitamin D Deficiency
Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 28, 2014