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Vitamin D for Polycystic Ovary Syndrome Clomiphene Resistant Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04010942
Recruitment Status : Completed
First Posted : July 8, 2019
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
Sara Abouelfath Abouelasrar Gad Dawoud, Ain Shams University

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

Condition or disease Intervention/treatment Phase
PCOS Vitamin D Deficiency Drug: Vit D Drug: Metformin Drug: Clomiphene Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Therapeutic Effect of Vitamin D3 Supplementation to Clomiphene Citrate Resistant Polycystic Ovary Syndrome Women
Actual Study Start Date : April 1, 2018
Actual Primary Completion Date : December 30, 2018
Actual Study Completion Date : March 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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 .

Drug: Vit D
Injection
Other Name: Devarol-S

Drug: Metformin
tablets
Other Name: Glucophage extended release

Drug: Clomiphene
Tablet
Other Name: Clomid

Placebo Comparator: 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 .

Drug: Metformin
tablets
Other Name: Glucophage extended release

Drug: Clomiphene
Tablet
Other Name: Clomid




Primary Outcome Measures :
  1. Follicle growth and maturation [ Time Frame: 11days ]
    Transvaginal ultrasound will be done every 48 hours at the start from day 10 of the cycle to assess if the follicle reaches 17-19 mm

  2. Change in Follicle growth and maturation at 3rd month [ Time Frame: 11 days ]
    Transvaginal ultrasound will be done every 48 hours at the start from day 10 of the cycle to assess if the follicle reaches 17-19 mm

  3. Change in Follicle growth and maturation at 5th month [ Time Frame: 11 days ]
    Transvaginal ultrasound will be done every 48 hours at the start from day 10 of the cycle to assess if the follicle reaches 17-19 mm


Secondary Outcome Measures :
  1. Occurence of Chemical pregnancy occurence [ Time Frame: recorded at any time point during the study whenever occurs up to 5 months ]
    Positive pregnancy test



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04010942


Locations
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Egypt
Ain Shams University Maternity hospital
Cairo, Egypt
Sponsors and Collaborators
Ain Shams University
Investigators
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Study Director: Reda MK Ghanem, Lecturer Obstetrics & Gynecology department Faculty of medicine, Ain shams University.
Study Director: Ahmed MN Hashaad, Professor Obstetrics & Gynecology department - Faculty of medicine, Ain shams University.
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Responsible Party: Sara Abouelfath Abouelasrar Gad Dawoud, Doctor, Ain Shams University
ClinicalTrials.gov Identifier: NCT04010942    
Other Study ID Numbers: VitDPcos
First Posted: July 8, 2019    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data for primary and secondary outcome measures will be available
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Within 9 months of study completion
Access Criteria: Requestors should sign a data access agreement. And requests will be revised

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polycystic Ovary Syndrome
Vitamin D Deficiency
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Metformin
Clomiphene
Hypoglycemic Agents
Physiological Effects of Drugs
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators