Vitamin D and Polycystic Ovarian Syndrome (PCOS)

NCT ID: NCT03989778

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2025-07-13

Brief Summary

Primary Objectives:

To evaluate the efficacy of metformin and Vitamin D supplementation on serum insulin and serum androgen levels (Total testosterone, Steroid Hormone Binding Globulin, Free Androgen Index) levels compared metformin alone in infertile Poly cystic ovarian females of reproductive age group.

Secondary Objectives:

To measure change in endometrial thickness/number of follicles and follicular size by day 12 trans-vaginal ultrasound in the intervention group i.e. combination of metformin and vitamin D supplementation

Detailed Description

Polycystic ovary syndrome (PCOS) as defined by "the presence of any two out of three criteria i.e. Oligo and/or anovulation, excess androgen activity and/or polycystic ovarian morphology on ultrasound", is a prevalent cause of female infertility. In the endocrine milieu of PCOS higher levels of insulin due to insulin resistance (IR) exert direct effects on the ovaries, release insulin-like growth factor 1 (IGF-1) from the liver and both then increase levels of testosterone. The resultant prevents the growth of ovarian follicles to acquire the required dimension for ovulation (i.e. > 10 mm) hence leading to anovulation and therefore subfertility. Vitamin D (VD) has found to be predominantly deficient in PCOS females, documented to cause IR giving rise to anovulatory cycles, hyperandrogenism and other significant features of PCOS. Therefore, we have hypothesized that treatment with VD in PCOS females can reduce IR, improve ovulation and signs of hyperandrogenism. Since Metformin is frequently prescribed for reducing IR and hence the treatment for anovulatory infertility in these females, we have planned to conduct an open label randomized control trial in PCOS infertile females who have vitamin D levels < than 25 ng/ml and are receiving Metformin therapy after ethical approval from Aga Khan University. The intervention group will receive VD Cholecalciferol (D2) 50,000 I.U once weekly for 12 weeks, followed by 50,000 I.U once every fortnight for 24 weeks with the Metformin treatment as prescribed by the physician whereas control group will receive Metformin treatment during the study period. We will compare change in number of dominant follicles (more than 10 mm) / endometrial thickness in both groups by Day 12 trans-vaginal ultrasound at the time of enrollment with scans done after 12 and 24 weeks. The other biochemical parameters [Total Testosterone, Steroid Hormone Binding Globulin, Free Androgen Index, Lipid Accumulation Product, Serum Insulin, Serum Triglycerides, Serum Calcium and Albumin] will be done at the time of recruitment in both the intervention and control groups and compared.

Conditions

Infertility, Female; Infertility; Vitamin D Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vitamin D supplement

The intervention group will receive VD Cholecalciferol (D2) 50,000 I.U once weekly for 12 weeks, followed by 50,000 I.U once every fortnight for 24 weeks with the Metformin treatment as prescribed by the physician whereas

Group Type: EXPERIMENTAL

Vitamin D

Intervention Type: DRUG

Vitamin D supplementation

Control

control group will receive Metformin treatment during the study period.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Vitamin D

Vitamin D supplementation

Intervention Type: DRUG

Other Intervention Names

Metformin

Eligibility Criteria

Inclusion Criteria

• Females with age range 18- 36 years, from all ethnic background having primary infertility with diagnosis of PCOS when at least 2 of these 3 elements are present: hyperandrogenism, chronic anovulation and polycystic ovaries and Vitamin D deficiency serum levels < 25 nmol/L

Exclusion Criteria

• Females with secondary Infertility
• Hypercalcemia (plasma calcium concentrations> 2.65 mmol/L)
• Exclude women with Tuberculosis or other granulomatous disorders.
• Women receiving vitamin D replacement, oral contraceptives, hormonal replacement therapy, glucocorticoids, calcium supplementation, insulin-sensitizing drugs(incretin mimetic drugs, thiazolidinedione, sulfonylurea), lipid-lowering drugs or other drugs affecting insulin sensitivity or serum androgens (e.g., niacin, corticosteroids, beta-blockers, calcium channel blockers, thiazide diuretics), anti-epileptics, anti-retroviral, cholestyramine, anti-fungal, statins, H2 blockers, immunosuppressants, chemotherapeutic agents, antimicrobials (Rifampicin, isoniazid, hydroqychloroquin) or any other drug modifying lipid metabolism in the previous 3 months prior to study
• Women with congenital adrenal hyperplasia, Cushing's syndrome, androgen-secreting tumors, type 2 diabetes mellitus, renal, hepatic or thyroid disorders, hyperparathyroidism, malabsorption syndromes, Chronic Kidney Disease Hepatic failure, cystic fibrosis, vaginal bleeding of unknown etiology Women Those who had Bariatric surgery will also be excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 36 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aga Khan University

OTHER

Sponsor Role: lead

Responsible Party

Rehana Rehman

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Dr Rehana Rehman

Karachi, Sindh, Pakistan

Site Status: RECRUITING

Dr Rehana Rehman

Karachi, Sindh, Pakistan

Site Status: RECRUITING

Countries

Pakistan

Central Contacts

Rehana K Rehman, PhD

Role: CONTACT

drrehana7@gmail.com

00922134864460 ext. 4460

Facility Contacts

Rehana Rehman

Role: primary

rehana.rehman@aku.edu

03072227775

Arfa Azhar

Role: backup

arfa.azhar@aku.edu

00922134864473 ext. 4473

Rehana Rehman

Role: primary

rehana.rehman@aku.edu

03072227775

Arfa Azhar

Role: backup

arfa.azhar@aku.edu

00922134864473 ext. 4473

Other Identifiers

124

Identifier Type: -

Identifier Source: org_study_id