Vitamin D for Polycystic Ovary Syndrome Clomiphene Resistant Women

NCT ID: NCT04010942

Last Updated: 2019-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-01
• Study Completion Date: 2019-03-30

Brief Summary

This study is determining the therapeutic effect of Vitamin D supplements to Pcos clomiphene resistant polycystic ovarian syndrome Women. Half of patients will receive Vitamin D with metformin while other half metformin only. Then both groups start clomiphene for 3 month

Detailed Description

Polycystic ovary syndrome (PCOS) is considered one of the most common endocrine disorders affecting women in their reproductive age. Genetically it is thought to be involving defects in primary cellular control mechanisms resulting in expression of chronic anovulation and androgen excess. Being familial condition , some researches showed it is autosomal dominant while others thought it is complex trait with oligogenic basis.

Diagnosing poly cystic ovary syndrome is based on finding two of three criteria according to Rotterdam consensus 2003 : oligo/anovulation, clinical/ biochemical signs of hyperandrogenism, ultrasound finding of polycystic ovaries. While insulin resistance which affects 50 - 70 % of PCOS patients is considered to be the main reason for hyperandrogenic features, PCOS also leads to various health problems including metabolic disorders (obesity - Diabetes Mellitus - Cardiovascular diseases) in addition to menstrual irregularities and infertility .

In PCOS women there is polymorphism in Vitamin-D receptor (VDR) gene associated with vitamin D level in blood . This gene is isolated from the female reproductive organs . In VDR null mice; uterine hypoplasia, impaired folliculogenesis and infertility is noted . That's why it is thought to be contributing in the genomic regulation of reproduction.

Several studies have investigated the effectiveness of Vitamin D supplementation to PCOS women they found that PCOS women have hypovitaminosis D3 , with increasing evidence that vitamin D affects insulin and glucose metabolism . vitamin D intake in PCOS women may improve hormonal profiles in addition to having anti-inflammatory and anti-oxidant effects . Another study concluded that Vitamin D and calcium supplementation to PCOS women have a positive effect on BMI, follicular maturation, regularity of menses, androgen related symptoms, infertility and insulin resistance . Moreover, Vitamin D has a crucial role in ovulation induction in women with PCOS.

Vitamin D and calcium in combination with metformin have significant effect on menstrual regulation and follicular development.

Insulin sensitizers such as metformin have been extensively investigated in the management of PCOS. Metformin decreases blood glucose levels by enhancing peripheral glucose uptake, decreasing intestinal glucose absorption and suppressing hepatic glucose levels. In anovulatory women with PCOS, metformin decreases insulin levels, luteinizing hormone (LH) production and circulating androgen levels.

Clomiphene citrate is an estrogen agonist and antagonist. It works by competitively binding estrogen receptors in the thalamus and as it remains in place for an extended period of time, it depletes the body's estrogen concentration at the hypothalamic level. As the body perceives low levels of estrogen, gonadotropin-releasing hormone (GnRH) is released which in turn stimulates pituitary release of follicle stimulating hormone ( FSH) which promotes follicular growth and maturation. If pregnancy is not achieved by 3-6 cycles, other treatments should be considered.

Conditions

PCOS; Vitamin D Deficiency

Study Design

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

Study Groups

Vitamin D

Group V : number of 60 women will receive 100000 IU Cholecalciferol Intramuscular every month + 2000 mg Metformin (oral: 2 tablets 1000 per day) for 5 months .

-after two months from the start:

Clomiphene citrate 100mg (2 tablets clomid 50mg each per day,from 2nd to 6th day of the cycle ) will be added every month starting from the 3rd month to the 5th month .

Group Type: ACTIVE_COMPARATOR

Vit D

Intervention Type: DRUG

Injection

Metformin

Intervention Type: DRUG

tablets

Clomiphene

Intervention Type: DRUG

Tablet

Control

Group C: number of 60 patients will receive Metformin 2000mg (oral: 2 tablets1000 mg per day) for months .

-after two months from the start:

Clomiphene citrate 100mg (2 tablets clomid 50mg each per day, from 2nd to 6th day of the cycle ) will be added every month starting from the 3rd month to the 5th month .

Group Type: PLACEBO_COMPARATOR

Metformin

Intervention Type: DRUG

tablets

Clomiphene

Intervention Type: DRUG

Tablet

Interventions

Vit D

Injection

Intervention Type: DRUG

Metformin

tablets

Intervention Type: DRUG

Clomiphene

Tablet

Intervention Type: DRUG

Other Intervention Names

Devarol-S; Glucophage extended release; Clomid

Eligibility Criteria

Inclusion Criteria

• Diagnosis of PCOS as defined by the Rotterdam criteria
• Females age 20-35 years old
• BMI 18-30 kg/m2
• 1ry or secondary infertility
• Clomiphene resistant ( patients didn't - show response: ovulate to dose of 200 mg clomid per day for 3 cycles )
• Willingness to comply with study protocol for 5 months
• Willingness to give written informed consent to participate in the study

Exclusion Criteria

• Previous metformin intake
• ovarian drilling
• tubal factor as evidenced by hysterosalpingogram or laparoscope
• endometrial pathology ex., polyp
• Myometrial pathology ex., adenomyosis or fibroid
• abnormal semen parameters
• Cushing syndrome
• Hyperprolactinemia
• Adrenal secreting tumor

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Sara Abouelfath Abouelasrar Gad Dawoud

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Reda MK Ghanem, Lecturer

Role: STUDY_DIRECTOR

Obstetrics & Gynecology department Faculty of medicine, Ain shams University.

Ahmed MN Hashaad, Professor

Role: STUDY_DIRECTOR

Obstetrics & Gynecology department - Faculty of medicine, Ain shams University.

Locations

Ain Shams University Maternity hospital

Cairo, , Egypt

Countries

Egypt

Other Identifiers

VitDPcos

Identifier Type: -

Identifier Source: org_study_id