Vitamin D for the Treatment of Women With Polycystic Ovary Syndrome (PCOS)

Vitamin D Supplementation in Polycystic Ovary Syndrome: a Randomized Controlled Trial.

The purpose of this study is to determine if vitamin D will improve insulin resistance, inflammation, and overall well-being in women with PCOS.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Dietary supplement: Vitamin D; Drug: Placebo

Detailed Description

As many cells throughout the body possess the vitamin D receptor, adequate vitamin D levels may be essential for multiple physiologic functions. In recent years, vitamin D insufficiency has been linked to insulin resistance, inflammation, poor psychological health, obesity, type 2 diabetes, and cardiovascular disease - these are also commonly found in women with Polycystic Ovary syndrome (PCOS). We believe that vitamin D insufficiency contributes to insulin resistance, inflammation, and psychological distress in women with PCOS. These adverse effects may ultimately increase the risk for serious long-term complications in PCOS, including type 2 diabetes and cardiovascular disease. The key objectives of this research study are to determine the effects of vitamin D supplementation on insulin resistance, inflammation, mood and overall well-being in women with PCOS.

The protocol has been modified by adding the following specific aim: To compare vascular function in healthy age and BMI similar matched women to PCOS women pre-treatment. Our hypothesis is that PCOS women will have greater attenuations in retinal vascular reactivity compared to healthy control women, demonstrating poorer endothelial function. We are currently recruiting healthy women who are age and BMI similar to the PCOS women and measure their retinal vascular reactivity for comparisons to the PCOS women's pre-treatment vascular reactivity. These healthy women will only have a baseline visit in which retinal vascular reactivity will be measured. They will not be enrolled in the placebo or Vitamin D randomization process as described above.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine, Penn State Milton S Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diagnosis of PCOS based on:

  • Eight or fewer menstrual periods per year or spontaneous intermenstrual periods of greater than or equal to 45 days, and
  • Elevated testosterone levels

Exclusion Criteria:

• Current Pregnancy or Nursing
• Elevated calcium
• Kidney Stones or kidney disease
• Current use of vitamin D (other than a multivitamin)
• Use of metformin or other insulin sensitizing drugs in the last 3 months
• Elevated prolactin or untreated thyroid disease
• Diabetes, Liver disease, Heart disease, or other serious medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo by mouth once daily for 12 weeks
Experimental: Vitamin D	Dietary supplement: Vitamin D; Vitamin D 300 mcg by mouth once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Quantitative Insulin Sensitivity Check Index (QUICKI)	Quantitative insulin sensitivity check index (QUICKI) is a validated measure of insulin sensitivity based on fasting insulin and glucose. Quantitative insulin sensitivity check index (QUICKI) = 1/[log(I(0)) + log(G(0))]).	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean High Sensitive C-reactive Protein (hsCRP)	High sensitive C-reactive protein (hsCRP) was assessed as a measure of inflammation.	Baseline and 12 weeks
Change From Baseline in Mean Systolic Blood Pressure	Blood pressure was measured in the right arm in the sitting position after a 15-minute rest.	Baseline and 12 weeks
Change From Baseline in Mean Diastolic Blood Pressure	Blood pressure was measured in the right arm in the sitting position after a 15-minute rest.	Baseline and 12 weeks
Change From Baseline in Mean Fasting Glucose	Glucose was assessed after 12 hours of fasting.	Baseline and 12 weeks
Change From Baseline in Mean Fasting Insulin	Insulin was assessed after 12 hours of fasting.	Baseline and 12 weeks
Change From Baseline in Mean 2-hour Glucose	Participants underwent a 75-gram oral glucose tolerance test, in which blood samples for glucose and insulin were obtained at 0 and 2 hours and used to calculate the insulin sensitivity index (ISI 0,120).	Baseline and 12 weeks
Change From Baseline in Mean 2-hour Insulin	Participants underwent a 75-gram oral glucose tolerance test, in which blood samples for glucose and insulin were obtained at 0 and 2 hours and used to calculate the insulin sensitivity index (ISI 0,120).	Baseline and 12 weeks
Change From Baseline in Mean Insulin Sensitivity Index (ISI 0,120)	Participants underwent a 75-g oral glucose tolerance test, in which blood samples for glucose and insulin were obtained at 0 and 120 minutes and used to calculate the insulin sensitivity index (ISI0,120). The ISI 0,120 = the glucose uptake rate divided by the mean plasma glucose divided by the log(mean serum insulin).	Baseline and 12 weeks
Change From Baseline in Mean Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is a validated measure of insulin resistance based on fasting insulin and glucose. HOMA-IR is calculated as the product of fasting glucose and insulin divided by 22.5.	Baseline and 12 weeks
Change From Baseline in Mean Total Cholesterol	Lipid profile was assessed after 12 hours of fasting.	Baseline and 12 weeks
Change From Baseline in Mean HDL Cholesterol	Lipid profile was assessed after 12 hours of fasting.	Baseline and 12 weeks
Change From Baseline in Mean LDL Cholesterol	Lipid profile was assessed after 12 hours of fasting.	Baseline and 12 weeks
Change From Baseline in Mean Triglycerides	Lipid profile was assessed after 12 hours of fasting.	Baseline and 12 weeks
Change From Baseline in Mean Total Testosterone	Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.	Baseline and 12 weeks
Change From Baseline in Mean Free Testosterone	Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.	Baseline and 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 25-hydroxyvitamin D	Total 25-hydroxyvitamin D was assayed by the Immunodiagnostic Systems radioimmunoassay.	Baseline and 12 weeks
Change From Baseline in Mean Vitamin D Binding Protein	Vitamin D binding protein levels were assessed as it has been linked with insulin resistance and type 2 diabetes.	Baseline and 12 weeks
Change From Baseline in Mean Intact Parathyroid Hormone (i-PTH)	Intact parathyroid hormone levels were assessed as they have been linked with obesity and insulin resistance.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Nazia Raja-Khan, M.D., Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Publications and helpful links

General Publications

• Raja-Khan N, Shah J, Stetter CM, Lott ME, Kunselman AR, Dodson WC, Legro RS. High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial. Fertil Steril. 2014 Jun;101(6):1740-6. doi: 10.1016/j.fertnstert.2014.02.021. Epub 2014 Mar 14.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: May 21, 2009
• First Submitted That Met QC Criteria: May 21, 2009
• First Posted (Estimate): May 22, 2009

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: November 20, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Inflammation; Vitamin D; Insulin resistance; Polycystic Ovary Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: 29714