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Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome

Primary Purpose

Anovulatory Infertility

Status
Recruiting
Phase
Phase 1
Locations
Pakistan
Study Type
Interventional
Intervention
Vitamin D
Active Comparator
Sponsored by
Aga Khan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anovulatory Infertility focused on measuring Poly cystic Ovarian Syndrome, randomized open label trial; delayed-start design, vitamin D, Pakistan

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria: Recently diagnosed PCOS with presence of at least 2 of these 3 elements: clinical or biochemical signs of hyperandrogenism, chronic anovulation and polycystic ovaries (1) (from reports of available routine TVS), with VDD serum levels VD <20 ng/ml(10), age range 18- 45 years, from all ethnic background will be included. Exclusion Criteria: : Exclusion of subjects will be done by the Co-Principal Investigators (Co-PI) after history, examination and complete evaluation in the respective clinics. All female subjects meeting any of the following criteria will be excluded from the study Pregnancy Hypercalcemia (plasma calcium concentrations> 2.65 mmol/L) Tuberculosis or other granulomatous disorders Chronic liver disease or alanine transaminase (ALT) level 3 times higher than the normal limit, chronic Kidney disease or serum creatinine >2.0 mg/dL, Drug Therapies: VD replacement ; participants who had received VD injection in the last 3 months prior to recruitment in the study, 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, immunosuppressant, chemotherapeutic agents, antimicrobials (Rifampicin, Isoniazid, Hydroxychloroquine) or any other drug modifying lipid metabolism in the previous 3 months prior to study Suffering from 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 or /and suffering from COVID-19 (within 3 months).

Sites / Locations

  • Aga Khan University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

VD supplementation

Control

Arm Description

Experimental Group (Group A; n=71): The intervention (experimental) group will receive VD injections 600,000 I.U I/M once with 1 gram calcium supplemental daily in the initial 12 weeks. After that standard PCOS care; i) Glucophage XR 750 mg (once for 15 days then twice daily) ii) progesterone supplementation (1 capsule Progeffik 100 mg every 3 weeks, then 1 week off) and iii) calcium supplements will be given for next 12 weeks.

Control Group (Group B; n=71): Participants will receive standard PCOS treatment; Glucophage XR 750 mg once at dinner for 15 days then twice daily and Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off for initial-- 12 weeks. Then VD supplementation (600,000 IUI/M) will be given once during the study period with Calcium 1000 mg/day and continued Standard PCOS treatment from 12- 24 weeks

Outcomes

Primary Outcome Measures

hyperandrogenism
hyperandrogenism by Free Androgen Index [Total Testosterone, Steroid Hormone Binding Globulin
insulin Resistance
HOMA-IR (serum Insulin, Fasting Blood Glucose)
oxidative stress
Total Antioxidant Capacity

Secondary Outcome Measures

Full Information

First Posted
September 5, 2023
Last Updated
September 26, 2023
Sponsor
Aga Khan University
Collaborators
Pakistan Science Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT06045351
Brief Title
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Official Title
Efficacy of Vitamin D Supplementation in Females With Polycystic Ovary Syndrome: a Randomized Open Label Delayed-start Design
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aga Khan University
Collaborators
Pakistan Science Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Poly cystic Ovarian Syndrome (PCOS) is an endocrine disorder of reproductive age defined by "the presence of any two out of three criteria: oligo and/or anovulation, excess androgen activity and/or polycystic ovarian morphology on ultrasound". Considering role of vitamin D (VD) (3, 4) and high prevalence (58%) of deficiency in PCOS of Pakistan. Researchers hypothesized that its correction would improve response to standard PCOS treatment. The objective is to compare PCOS parameters in intervention group (Group A) receiving VD supplementation and then PCOS care with control group (Group B) receiving standard PCOS care and then VD supplementation. A randomized open label trial: delayed-start design will be conducted on VD deficient PCOS females VD < 20ng/ml ; Group A will receive VD injections 600,000 I.U I/M once with 1 gram calcium supplement daily in the initial 12 weeks. After that standard PCOS care; i) Glucophage XR 750 mg (once for 15 days then twice daily) ii) progesterone supplementation (1 capsule Progeffik 100 mg every 3 weeks, then 1 week off) and iii) calcium supplements will be given for next 12 weeks. PCOS females in Group B will receive standard PCOS care (same) with addition of VD and calcium supplementation after 12 weeks till study end point. Study outcomes will be comparison of i) hyperandrogenism by Free Androgen Index [Total Testosterone, Steroid Hormone Binding Globulin ii) insulin Resistance by HOMA-IR (serum Insulin, Fasting Blood Glucose) and iii) oxidative stress by Total Antioxidant Capacity after 24-weeks in these Groups'd levels after supplementation will be assessed for confirmation of correction and calcium and albumin levels for detection of hypercalcemia. Results of this study will inform the clinicians to add VD before or after the standard PCOS care for rectification of endocrine and metabolic derangements as a cost-effective treatment and prevention strategy in these females.
Detailed Description
This study will comprise of two groups (A and B) with 71 participants in each group carried for a duration of 24 weeks. Intervention Details for Group A (Duration 1-12 weeks): Participants will be given Vitamin D (VD) supplementation at a dose of 600,000 IU along with Calcium 1000 mg/day. Mid-Point (At 12 weeks): Patients will have a consultation for clinical interpretation. They will undergo biochemical assessment, including the estimation of Insulin Resistance, Free Androgen Index, and Total Antioxidant Capacity. After 12 weeks They will receive standard treatment for Polycystic Ovary Syndrome (PCOS), which includes Glucophage XR 750 mg once at dinner for 15 days, then twice daily. Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off and Calcium 1000 mg/day Intervention Details for Group B (Duration 1-12 weeks): Participants in Group B will receive standard PCOS treatment mentioned earlier: Glucophage XR 750 mg once at dinner for 15 days, then twice daily. Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off. Additionally, they receive Calcium 1000 mg/day. Mid-Point (At 12 weeks): Patients will have a consultation for clinical interpretation. They will undergo biochemical assessment, including the estimation of Insulin Resistance, Free Androgen Index, and Total Antioxidant Capacity. Intervention Details for Group A (After 12 weeks) They will receive VD supplementation (600,000 IU) during this time and continue to receive Calcium 1000 mg/day. Calculations of HOMA-IR and Free Androgen Index will be done at 12 and 24 weeks and the results will be compared. {HOMA-IR: HOMA- IR index, a commonly used marker of IR, will be calculated using the formula: HOMA-IR = fasting glucose levels [mmol/L] × fasting insulin levels [μU/mL]/22.5 Free Androgen Index will be derived from TT and SHBG, normally measured in nanomoles per liter. FAI =100 (TT /SHBG)}

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anovulatory Infertility
Keywords
Poly cystic Ovarian Syndrome, randomized open label trial; delayed-start design, vitamin D, Pakistan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Infertile females with Polycystic Ovarian Syndrome
Masking
None (Open Label)
Allocation
Randomized
Enrollment
142 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VD supplementation
Arm Type
Experimental
Arm Description
Experimental Group (Group A; n=71): The intervention (experimental) group will receive VD injections 600,000 I.U I/M once with 1 gram calcium supplemental daily in the initial 12 weeks. After that standard PCOS care; i) Glucophage XR 750 mg (once for 15 days then twice daily) ii) progesterone supplementation (1 capsule Progeffik 100 mg every 3 weeks, then 1 week off) and iii) calcium supplements will be given for next 12 weeks.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Control Group (Group B; n=71): Participants will receive standard PCOS treatment; Glucophage XR 750 mg once at dinner for 15 days then twice daily and Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off for initial-- 12 weeks. Then VD supplementation (600,000 IUI/M) will be given once during the study period with Calcium 1000 mg/day and continued Standard PCOS treatment from 12- 24 weeks
Intervention Type
Drug
Intervention Name(s)
Vitamin D
Other Intervention Name(s)
Experimental, Group A
Intervention Description
Intervention Group Initial 12 weeks; VD supplementation (600,000 IU I/M) once during the study period Elemental calcium 1000 mg/day From 12-24 weeks: Standard PCOS; Glucophage XR 750 mg once at dinner for 15 days then twice daily Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off Calcium 1000 mg/day
Intervention Type
Other
Intervention Name(s)
Active Comparator
Other Intervention Name(s)
Group B
Intervention Description
Active Comparator (Group B; n=71): Initial-- 12 weeks; Standard PCOS; Glucophage XR 750 mg once at dinner for 15 days then twice daily Capsule Progeffik 100 mg once at night every 3 weeks, then 1 week off From 12- 24 weeks VD supplementation (600,000 IUI/M) once during the study period Calcium 1000 mg/day Standard PCOS Continued
Primary Outcome Measure Information:
Title
hyperandrogenism
Description
hyperandrogenism by Free Androgen Index [Total Testosterone, Steroid Hormone Binding Globulin
Time Frame
24 weeks
Title
insulin Resistance
Description
HOMA-IR (serum Insulin, Fasting Blood Glucose)
Time Frame
24 weeks
Title
oxidative stress
Description
Total Antioxidant Capacity
Time Frame
24 weeks

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Recently diagnosed PCOS with presence of at least 2 of these 3 elements: clinical or biochemical signs of hyperandrogenism, chronic anovulation and polycystic ovaries (1) (from reports of available routine TVS), with VDD serum levels VD <20 ng/ml(10), age range 18- 45 years, from all ethnic background will be included. Exclusion Criteria: : Exclusion of subjects will be done by the Co-Principal Investigators (Co-PI) after history, examination and complete evaluation in the respective clinics. All female subjects meeting any of the following criteria will be excluded from the study Pregnancy Hypercalcemia (plasma calcium concentrations> 2.65 mmol/L) Tuberculosis or other granulomatous disorders Chronic liver disease or alanine transaminase (ALT) level 3 times higher than the normal limit, chronic Kidney disease or serum creatinine >2.0 mg/dL, Drug Therapies: VD replacement ; participants who had received VD injection in the last 3 months prior to recruitment in the study, 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, immunosuppressant, chemotherapeutic agents, antimicrobials (Rifampicin, Isoniazid, Hydroxychloroquine) or any other drug modifying lipid metabolism in the previous 3 months prior to study Suffering from 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 or /and suffering from COVID-19 (within 3 months).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rehana Rehman, PhD
Phone
00922134864460
Ext
4460
Email
drrehana7@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rehana Rehman, PhD
Organizational Affiliation
Aga Khan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aga Khan University Hospital
City
Karachi
State/Province
Sindh
ZIP/Postal Code
75500
Country
Pakistan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rehana Rehman, PhD
Phone
03072227775
Email
rehana.rehman@aku.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome

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