Vitamin D Treatment, Pharmacogenetics and Glucose Metabolism
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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 |
- 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 ]
- 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 |
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| Contact: Elisabeth Lerchbaum, MD | 0043-316-385-81144 | elisabeth.lerchbaum@medunigraz.at |
| 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 | |
| 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: | June 3, 2013 |
| 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:
|
Polycystic Ovary Syndrome Vitamin D Deficiency 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 Bone Density Conservation Agents Physiological Effects of Drugs Pharmacologic Actions Micronutrients Growth Substances |
ClinicalTrials.gov processed this record on June 18, 2013