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

• Sponsor: Milton S. Hershey Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00907153
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2
• Duration (Months): 64
• Patients Per Site Per Month: 0.6

Study Details

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
• 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 1, 2009
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Sep 1, 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) [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) [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 [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 [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 [Baseline and 12 weeks]

   Glucose was assessed after 12 hours of fasting.

5. Change From Baseline in Mean Fasting Insulin [Baseline and 12 weeks]

   Insulin was assessed after 12 hours of fasting.

6. Change From Baseline in Mean 2-hour Glucose [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 [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) [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) [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 [Baseline and 12 weeks]

    Lipid profile was assessed after 12 hours of fasting.

11. Change From Baseline in Mean HDL Cholesterol [Baseline and 12 weeks]

    Lipid profile was assessed after 12 hours of fasting.

12. Change From Baseline in Mean LDL Cholesterol [Baseline and 12 weeks]

    Lipid profile was assessed after 12 hours of fasting.

13. Change From Baseline in Mean Triglycerides [Baseline and 12 weeks]

    Lipid profile was assessed after 12 hours of fasting.

14. Change From Baseline in Mean Total Testosterone [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 [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 [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 [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) [Baseline and 12 weeks]

   Intact parathyroid hormone levels were assessed as they have been linked with obesity and insulin resistance.

Eligibility Criteria

Criteria

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

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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
• Last Update Posted: Dec 19, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Nazia Raja-Khan, M.D., Assistant Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Milton S. Hershey Medical Center: Polycystic Ovary Syndrome; Vitamin D; Insulin resistance; Inflammation
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Syndrome; Vitamin D

Study Results

Participant Flow

Recruitment Details	36 patients were screened for eligibility between July 2009 and November 2010 at Medicine and Obstetrics and Gynecology clinics at an academic medical center in Hershey, PA.
Pre-assignment Detail	28 of 36 participants were randomized. Of those not randomized, 3 did not meet inclusion criteria, 3 declined to participate, and 2 were not randomized for other reasons.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Period Title: Overall Study
STARTED	13	15
COMPLETED	11	11
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Vitamin D	Placebo	Total
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks	Total of all reporting groups
Overall Participants	13	15	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.2 (5.2)	28.7 (5.6)	28.5 (5.3)
Sex: Female, Male (Count of Participants)
Female	13 100%	15 100%	28 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 7.7%	0 0%	1 3.6%
White	10 76.9%	14 93.3%	24 85.7%
More than one race	1 7.7%	0 0%	1 3.6%
Unknown or Not Reported	1 7.7%	1 6.7%	2 7.1%
Region of Enrollment (participants) [Number]
United States	13 100%	15 100%	28 100%
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	37.20 (4.53)	35.09 (9.81)	36.1 (7.8)
Systolic blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	117.46 (10.00)	113.91 (10.21)	115.56 (10.11)
Diastolic blood pressure (mm hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm hg]	79.08 (8.28)	74.88 (7.72)	76.83 (7.98)
25-hydroxyvitamin D (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	19.95 (9.47)	22.20 (6.86)	21.15 (8.10)
Vitamin D binding protein (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	30.46 (8.53)	31.95 (7.54)	31.34 (8.04)
Intact parathyroid hormone (i-PTH) (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	40.81 (27.34)	33.17 (17.73)	36.72 (22.19)
Fasting glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	84.92 (9.46)	83.73 (9.33)	84.29 (9.23)
Fasting insulin (uU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [uU/mL]	26.31 (9.60)	27.13 (15.79)	26.75 (13.05)
2-hour glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	122.08 (36.29)	110.07 (23.68)	115.64 (30.22)
2-hour insulin (uU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [uU/mL]	214.69 (146.41)	107.07 (55.20)	157.04 (118.72)
Insulin sensitivity index 0,120 (mg·l^2/mmol·mU·min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg·l^2/mmol·mU·min]	55.55 (23.26)	63.56 (16.37)	59.84 (19.57)
Quantitative Insulin Sensitivity Check Index (QUICKI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.302 (0.014)	0.307 (0.029)	0.305 (0.022)
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.47 (1.82)	5.80 (3.90)	5.65 (2.93)
Total cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	172.00 (42.70)	184.27 (32.52)	178.57 (37.38)
HDL cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	45.54 (17.60)	37.00 (10.83)	40.96 (14.74)
LDL cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	98.62 (36.96)	117.33 (28.56)	108.64 (33.47)
Triglyecrides (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	139.08 (71.61)	149.47 (85.46)	144.64 (78.07)
High sensitive C-reactive protein (hsCRP) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	7.95 (5.24)	4.42 (4.34)	6.1 (5.0)
Total testosterone (ng/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/dL]	54.23 (28.16)	41.27 (17.29)	48.48 (23.03)
Free testosterone (ng/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/dL]	19.08 (15.79)	14.00 (10.88)	16.89 (13.33)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [units on a scale]	-0.008	0.009

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.017
	Confidence Interval	(2-Sided) 95%; -0.034 to -0.000
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Mean High Sensitive C-reactive Protein (hsCRP)
Description	High sensitive C-reactive protein (hsCRP) was assessed as a measure of inflammation.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/L]	0.90	2.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.14
	Confidence Interval	(2-Sided) 95%; -5.89 to 3.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Mean Systolic Blood Pressure
Description	Blood pressure was measured in the right arm in the sitting position after a 15-minute rest.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mm Hg]	0.64	4.29

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.65
	Confidence Interval	(2-Sided) 95%; -14.32 to 7.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Mean Diastolic Blood Pressure
Description	Blood pressure was measured in the right arm in the sitting position after a 15-minute rest.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mm Hg]	-0.91	5.60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.51
	Confidence Interval	(2-Sided) 95%; -12.07 to -0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Mean Fasting Glucose
Description	Glucose was assessed after 12 hours of fasting.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/dL]	-0.70	-6.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.28
	Confidence Interval	(2-Sided) 95%; -3.97 to 16.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Mean Fasting Insulin
Description	Insulin was assessed after 12 hours of fasting.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [uU/mL]	13.04	-0.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	13.84
	Confidence Interval	(2-Sided) 95%; -210.29 to 37.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Mean 2-hour Glucose
Description	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).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/dL]	-11.66	1.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.80
	Confidence Interval	(2-Sided) 95%; -42.94 to 17.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Mean 2-hour Insulin
Description	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).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [uU/mL]	-62.02	13.06

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-75.08
	Confidence Interval	(2-Sided) 95%; -161.9 to 11.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Mean Insulin Sensitivity Index (ISI 0,120)
Description	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).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg·l^2/mmol·mU·min]	6.67	5.94

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; -32.59 to 34.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Mean Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Description	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.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [units on a scale]	2.57	-0.51

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.08
	Confidence Interval	(2-Sided) 95%; -1.84 to 7.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Mean Total Cholesterol
Description	Lipid profile was assessed after 12 hours of fasting.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/dL]	-1.69	-1.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -24.43 to 24.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Mean HDL Cholesterol
Description	Lipid profile was assessed after 12 hours of fasting.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/dL]	-0.70	1.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.93
	Confidence Interval	(2-Sided) 95%; -10.12 to 6.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in Mean LDL Cholesterol
Description	Lipid profile was assessed after 12 hours of fasting.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/dL]	-0.12	-0.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -20.29 to 20.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in Mean Triglycerides
Description	Lipid profile was assessed after 12 hours of fasting.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/dL]	-2.21	-12.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	10.24
	Confidence Interval	(2-Sided) 95%; -34.61 to 55.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change From Baseline in Mean Total Testosterone
Description	Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [ng/dL]	3.01	10.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; -22.81 to 8.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change From Baseline in Mean Free Testosterone
Description	Total and free testosterone levels were assessed from blood samples to evaluate effects on hyperandrogenemia in PCOS.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [ng/dL]	2.67	5.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.15
	Confidence Interval	(2-Sided) 95%; -8.70 to 2.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Other Pre-specified Outcome

Title	Change From Baseline in Mean 25-hydroxyvitamin D
Description	Total 25-hydroxyvitamin D was assayed by the Immunodiagnostic Systems radioimmunoassay.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [ng/mL]	45.63	1.32

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	44.31
	Confidence Interval	(2-Sided) 95%; 27.13 to 61.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Other Pre-specified Outcome

Title	Change From Baseline in Mean Vitamin D Binding Protein
Description	Vitamin D binding protein levels were assessed as it has been linked with insulin resistance and type 2 diabetes.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [mg/dL]	1.01	-0.55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95%; -2.08 to 5.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Other Pre-specified Outcome

Title	Change From Baseline in Mean Intact Parathyroid Hormone (i-PTH)
Description	Intact parathyroid hormone levels were assessed as they have been linked with obesity and insulin resistance.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

All analyses were by intention to treat. All randomized participants received and ingested the treatment that they were randomly assigned to.

Arm/Group Title	Vitamin D	Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks	Placebo: Placebo by mouth once daily for 12 weeks
Measure Participants	13	15
Mean (95% Confidence Interval) [pg/mL]	-24.28	-16.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments
	Method	Regression, Linear
	Comments	Model-based differences adjusted for oral contraceptive use and season.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.84
	Confidence Interval	(2-Sided) 95%; -29.34 to 13.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Twelve weeks.
Arm/Group Title	Vitamin D		Placebo
Arm/Group Description	Vitamin D: Vitamin D 300 mcg by mouth once daily for 12 weeks		Placebo: Placebo by mouth once daily for 12 weeks
All Cause Mortality
	Vitamin D		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vitamin D		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.