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

• ClinicalTrials.gov Identifier: NCT00907153
• Recruitment Status: Completed
• First Posted: May 22, 2009
• Results First Posted: December 19, 2017
• Last Update Posted: December 19, 2017
• Sponsor: Milton S. Hershey Medical Center
• Information provided by (Responsible Party): Nazia Raja-Khan, Milton S. Hershey Medical Center

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Polycystic Ovary Syndrome	Dietary Supplement: Vitamin D; Drug: Placebo	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Vitamin D Supplementation in Polycystic Ovary Syndrome: a Randomized Controlled Trial.
• Study Start Date: May 2009
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: September 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vitamin D	Dietary Supplement: Vitamin D; Vitamin D 300 mcg by mouth once daily for 12 weeks
Placebo Comparator: Placebo	Drug: Placebo; Placebo by mouth once daily for 12 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Mean Quantitative Insulin Sensitivity Check Index (QUICKI) [ Time Frame: Baseline and 12 weeks ]
   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))]).

Secondary Outcome Measures :

1. Change From Baseline in Mean High Sensitive C-reactive Protein (hsCRP) [ Time Frame: Baseline and 12 weeks ]
   High sensitive C-reactive protein (hsCRP) was assessed as a measure of inflammation.
2. Change From Baseline in Mean Systolic Blood Pressure [ Time Frame: Baseline and 12 weeks ]
   Blood pressure was measured in the right arm in the sitting position after a 15-minute rest.
3. Change From Baseline in Mean Diastolic Blood Pressure [ Time Frame: Baseline and 12 weeks ]
   Blood pressure was measured in the right arm in the sitting position after a 15-minute rest.
4. Change From Baseline in Mean Fasting Glucose [ Time Frame: Baseline and 12 weeks ]
   Glucose was assessed after 12 hours of fasting.
5. Change From Baseline in Mean Fasting Insulin [ Time Frame: Baseline and 12 weeks ]
   Insulin was assessed after 12 hours of fasting.
6. Change From Baseline in Mean 2-hour Glucose [ Time Frame: Baseline and 12 weeks ]
   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).
7. Change From Baseline in Mean 2-hour Insulin [ Time Frame: Baseline and 12 weeks ]
   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).
8. Change From Baseline in Mean Insulin Sensitivity Index (ISI 0,120) [ Time Frame: Baseline and 12 weeks ]
   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).
9. Change From Baseline in Mean Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Baseline and 12 weeks ]
   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.
10. Change From Baseline in Mean Total Cholesterol [ Time Frame: Baseline and 12 weeks ]
    Lipid profile was assessed after 12 hours of fasting.
11. Change From Baseline in Mean HDL Cholesterol [ Time Frame: Baseline and 12 weeks ]
    Lipid profile was assessed after 12 hours of fasting.
12. Change From Baseline in Mean LDL Cholesterol [ Time Frame: Baseline and 12 weeks ]
    Lipid profile was assessed after 12 hours of fasting.
13. Change From Baseline in Mean Triglycerides [ Time Frame: Baseline and 12 weeks ]
    Lipid profile was assessed after 12 hours of fasting.
14. Change From Baseline in Mean Total Testosterone [ Time Frame: Baseline and 12 weeks ]
    Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.
15. Change From Baseline in Mean Free Testosterone [ Time Frame: Baseline and 12 weeks ]
    Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Pennsylvania

Penn State College of Medicine, Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States, 17033

Sponsors and Collaborators

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

More Information

Publications of Results:

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.

• Responsible Party: Nazia Raja-Khan, M.D., Assistant Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT00907153
• Other Study ID Numbers: 29714
• First Posted: May 22, 2009
• Results First Posted: December 19, 2017
• Last Update Posted: December 19, 2017
• Last Verified: November 2017

Keywords provided by Nazia Raja-Khan, Milton S. Hershey Medical Center:

Polycystic Ovary Syndrome; Vitamin D; Insulin resistance; Inflammation

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Syndrome; Disease; Pathologic Processes; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases; Vitamin D; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents