Health Benefits of Vitamin D and Calcium in Women With PCOS (Polycystic Ovarian Syndrome)

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00743574
• Collaborator: National Center for Research Resources (NCRR) (NIH)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 54
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The investigators conducted a prospective un-blinded pilot study of Vitamin D plus Calcium (Ca) supplementation in overweight (BMI > 27) premenopausal women diagnosed with Polycystic Ovarian Syndrome (PCOS), as defined by the Rotterdam Criteria, 2003, and who were deficient in vitamin D as reflected by serum 25-hydroxy (25-OH) vitamin D (serum levels < 20 ng/mL).

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovarian Syndrome; Vitamin D Deficiency	Dietary Supplement: Vitamin D2 (Ergocalciferol); Drug: Medroxyprogesterone (Provera); Dietary Supplement: Vitamin D3 (Cholecalciferol); Dietary Supplement: Elemental Calcium	N/A

Detailed Description

We had hypothesized that in women with PCOS, administering optimal daily doses of vitamin D3, as recommended by the National Academy of Sciences, 2000IU Cholecalciferol and 1000mg of calcium, both per oral (PO), over a three month period will improve their metabolic picture, and possibly hormone profile.

Over the course of the trial, after the first 5 subjects had completed 3 month intervention,we observed that daily 2000IU D3 dosing regime was inadequate in normalizing vitamin D status in the study population; the dosing regimen was therefore modified to include weekly supplementation with 50,000IU D2 in addition to daily dosing with 2000IU D3.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Health Benefits of Vitamin D and Calcium in Women With PCOS (Polycystic Ovarian Syndrome)
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Vitamin D plus Calcium (Ca) supplementation

Dietary Supplement: Vitamin D2 (Ergocalciferol); 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months); Drug: Medroxyprogesterone (Provera); 10mg, PO, daily for ten days; Dietary Supplement: Vitamin D3 (Cholecalciferol); 2,000IU (or 2 tablets), PO, daily (supplements taken for three months); Dietary Supplement: Elemental Calcium; 1,000mg (or 2 tablets), PO, daily (supplements taken for three months)

Outcome Measures

Primary Outcome Measures

1. Serum HbA1C at 3 Months [Completion]

   Fasting HbA1C levels at study completion after 3 month treatment

2. Fasting Insulin Levels at Study Completion After 3 Month Treatment [3 months intervention]

   Fasting insulin levels at study completion after 3 month treatment

3. Fasting Glucose Levels at Completion of Treatment, at 3 Months [3 months]

   Fasting glucose levels drawn after 3 months completion during oral GTT

4. AUC (Area Under a Curve at 0, 0.5, 1, 1.5 and 2 Hours) Insulin During 2 Hour GTT at Completion, at 3 Months [3 months]

   Following 3 months intervention, AUC insulin was determined during 2 hour oral GTT

5. AUC (Area Under the Curve at 0, 0.5, 1, 1.5 and 2 Hours) During Oral GTT at Completion, at 3 Months [3 months]

   AUC (Area under the curve at 0, 0.5, 1, 1.5 and 2 hours)for glucose was determined at completion of 3 months intervention for 2 hour oral GTT

Secondary Outcome Measures

1. Serum Levels of C-reactive Protein at Completion of 3 Months Treatment [3 months]

   Serum levels of C-reactive protein upon completion, at 3 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Premenopausal women (ages 18-40 years) with normal thyroid function and prolactin levels.

• PCOS diagnosis based on Rotterdam criteria: presence of at least 2 of the following criteria:

• oligomenorrhea-menstrual cycles > 35 day intervals

• hyperandrogenemia (elevated serum testosterone [free or total] &/or androstenedione levels) or features of hyperandrogenism i.e. acne or hirsuitism [Ferriman-Gallaway score > 3]

• polycystic ovaries on vaginal ultrasound as defined by ESHRE/ASRM criteria (ovarian volume ≥ 10mL or ≥ 12 follicles of diameter between 2-9mm in at least one ovary)

• Overweight (BMI ≥ 27 Kg/m2)

• Biochemical evidence of Vitamin D insufficiency (i.e. serum 25 OHD levels < 20ng/mL)

Exclusion Criteria:

• Pregnancy

• Known causes of oligomenorrhea other than PCOS, e.g. hypothyroidism/Cushing's Disease/late onset congenital adrenal hyperplasia (fasting 17-alphahydroxyprogesterone levels < 200ng/dL)

• Use of hormonal treatment (birth control pill/patch/depot medroxyprogesterone/medroxyprogesterone) within 3 months of the study onset.

• Use insulin sensitizers (metformin, sulfonylureas, TZDs, incretins) within 3 months of the study onset.

• Use of lipid lowering agents or medications known to influence insulin sensitivity (e.g. niacin, corticosteroids, beta blockers, calcium channel blockers, thiazide diuretics) or influence serum androgens (estrogen, anti-androgens, androgens) within 3 months of the study onset.

• Known history of renal calculi or current use of Calcium and Vitamin D supplements.

• Spanish Speaking.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale-New Haven Hospital-Women's Center	New Haven	Connecticut	United States	06520-8063

Sponsors and Collaborators

• Yale University
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Lubna Pal, MBBS,MRCOG,MSc., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00743574
• Other Study ID Numbers: YaleU-0807003992; YCCI-CARE Grant #UL1RR024139
• First Posted: Aug 29, 2008
• Last Update Posted: Aug 13, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Vitamin D Deficiency; Syndrome; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Medroxyprogesterone Acetate; Medroxyprogesterone; Calcium

Study Results

Participant Flow

Recruitment Details	Subjects recruited through flyers, medical clinics, internet postings May 2008-February 2010
Pre-assignment Detail	Some subjects did not follow through with eligibility testing or had further exclusions, such as scheduling difficulties.

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Period Title: Overall Study
STARTED	36
Dropped Out Before Eligibility Testing	13
Further Exclusions	8
Dropped Out After Initiating Trial	3
COMPLETED	12
NOT COMPLETED	24

Baseline Characteristics

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.42 (6.11)
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%
Baseline HbA1C levels (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	5.37 (0.53)
Baseline insulin levels (µIU/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [µIU/ml]	24.92 (15.42)
Baseline glucose levels (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	103.79 (22.83)
Baseline AUC insulin (µIU/ml/120 min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [µIU/ml/120 min]	16136.50 (10086.29)
Baseline AUC for glucose (mg/min/120min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/min/120min]	16648.41 (3949.98)
Baseline C Reactive protein level (mg/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/L]	5.72 (1.51-13.93)

Outcome Measures

1. Secondary Outcome

Title	Serum Levels of C-reactive Protein at Completion of 3 Months Treatment
Description	Serum levels of C-reactive protein upon completion, at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

All subjects who completed treatment for 3 months

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Measure Participants	12
Median (Inter-Quartile Range) [mg/L]	5.3

2. Primary Outcome

Title	Serum HbA1C at 3 Months
Description	Fasting HbA1C levels at study completion after 3 month treatment
Time Frame	Completion

Outcome Measure Data

Analysis Population Description

Number determined by those who completed all interventions and procedures.

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Measure Participants	12
Mean (Standard Deviation) [percentage]	5.55 (0.66)

3. Primary Outcome

Title	Fasting Insulin Levels at Study Completion After 3 Month Treatment
Description	Fasting insulin levels at study completion after 3 month treatment
Time Frame	3 months intervention

Outcome Measure Data

Analysis Population Description

Number determined by all those who completed all interventions and procedures.

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Measure Participants	12
Mean (Standard Deviation) [µIU/ml]	25.17 (13.67)

4. Primary Outcome

Title	Fasting Glucose Levels at Completion of Treatment, at 3 Months
Description	Fasting glucose levels drawn after 3 months completion during oral GTT
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Number determined based on all interventions and procedures completed.

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Measure Participants	12
Mean (Standard Deviation) [mg/dl]	103.79 (22.83)

5. Primary Outcome

Title	AUC (Area Under a Curve at 0, 0.5, 1, 1.5 and 2 Hours) Insulin During 2 Hour GTT at Completion, at 3 Months
Description	Following 3 months intervention, AUC insulin was determined during 2 hour oral GTT
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Number determined by completion of all study interventions and procedures

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Measure Participants	12
Mean (Standard Deviation) [µIU/ml/120min]	16715.57 (10371.76)

6. Primary Outcome

Title	AUC (Area Under the Curve at 0, 0.5, 1, 1.5 and 2 Hours) During Oral GTT at Completion, at 3 Months
Description	AUC (Area under the curve at 0, 0.5, 1, 1.5 and 2 hours)for glucose was determined at completion of 3 months intervention for 2 hour oral GTT
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Number determined by all participants who completed all interventions and procedures

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
Measure Participants	12
Mean (Standard Deviation) [mg/min/120min]	16726.56 (3941.80)

Adverse Events

Arm/Group Title	Vitamin D Plus Calcium (Ca) Supplementation
Arm/Group Description	Vitamin D3 (Cholecalciferol) : 2,000IU (or 2 tablets), PO, daily (supplements taken for three months) Elemental Calcium : 1,000mg (or 2 tablets), PO, daily (supplements taken for three months) Vitamin D2 (Ergocalciferol) : 50,000IU (or 1 tablet), PO, monthly (supplements to be taken for three months) Medroxyprogesterone (Provera) : 10mg, PO, daily for ten days
All Cause Mortality
	Vitamin D Plus Calcium (Ca) Supplementation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vitamin D Plus Calcium (Ca) Supplementation
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D Plus Calcium (Ca) Supplementation
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

Limitations/Caveats

No limitations

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.