PCOSPhase 4NCT04010942
Vitamin D for Polycystic Ovary Syndrome Clomiphene Resistant Women
A Phase 4 study testing Vit D, Metformin and Clomiphene in people with PCOS and Vitamin D Deficiency, run by Ain Shams University at 1 site in Egypt.
Trial 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 Read more about this study
- Who is it for?
- Ages 20 to 35 years, women only
- Conditions the study is for
- PCOS, Vitamin D Deficiency
- What is being tested?
- Vit D, Metformin and Clomiphene
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Apr 2018to 30 Mar 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Cushing syndrome
- Hyperprolactinemia
- Adrenal secreting tumor
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Therapeutic Effect of Vitamin D3 Supplementation to Clomiphene Citrate Resistant Polycystic Ovary Syndrome Women
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
Read the 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
- Being tested
- Vit D, Metformin, Clomiphene
- Medical subject headings
- Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vit DDrug
Also called Devarol-S
Injection
MetforminDrug
Also called Glucophage extended release
tablets
ClomipheneDrug
Also called Clomid
Tablet
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D | Active comparator | 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 . Receives: Drug: Vit D; Drug: Metformin; Drug: Clomiphene |
| Control | Placebo comparator | 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 . Receives: Drug: Metformin; Drug: Clomiphene |
What is being measured
The primary outcome is the main question the study is designed to answer.
Follicle growth and maturation
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
Measured: 11days
Change in Follicle growth and maturation at 3rd month
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
Measured: 11 days
Change in Follicle growth and maturation at 5th month
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
Measured: 11 days
Secondary outcomes (1)
Occurence of Chemical pregnancy occurence
Positive pregnancy test
Measured: recorded at any time point during the study whenever occurs up to 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2019
- Study start1 Apr 2018
- Primary completion30 Dec 2018
- Study completion30 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PCOSStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sara Abouelfath Abouelasrar Gad Dawoud, Ain Shams University
- Investigators
- Reda MK Ghanem, Lecturer, Study director, Obstetrics & Gynecology department Faculty of medicine, Ain shams University.Ahmed MN Hashaad, Professor, Study director, Obstetrics & Gynecology department - Faculty of medicine, Ain shams University.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04010942
- Sponsor's protocol ID
- VitDPcos
- Status last verified
- Jul 2019
- First submitted
- 2 Jul 2019
- Last updated
- 8 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data for primary and secondary outcome measures will be available
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Effect of Vitamin D3 Supplementation to Clomiphene Citrate Resistant Polycystic Ovary Syndrome Women
- ClinicalTrials.gov ID
- NCT04010942
- Acronym / sponsor ID
- VitDPcos
- Conditions
- PCOS, Vitamin D Deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 30 Dec 2018 (actual)
- Study completion
- 30 Mar 2019 (actual)
- First posted
- 8 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D | Active comparator | Drug: Vit D, Drug: Metformin, Drug: ClomipheneGroup 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 . |
| Control | Placebo comparator | Drug: Metformin, Drug: ClomipheneGroup 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 . |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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 )
Key exclusion criteria (9 listed)
- Previous metformin intake
- ovarian drilling
- tubal factor as evidenced by hysterosalpingogram or laparoscope
- endometrial pathology ex., polyp
- Myometrial pathology ex., adenomyosis or fibroid
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vit DAlso: Devarol-SInjection | Drug | Vitamin D |
| MetforminAlso: Glucophage extended releasetablets | Drug | Control, Vitamin D |
| ClomipheneAlso: ClomidTablet | Drug | Control, Vitamin D |
Primary outcome
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
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
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
1 secondary outcome
Occurence of Chemical pregnancy occurence
Time frame: recorded at any time point during the study whenever occurs up to 5 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2019.
- Individual participant dataSharing planned: Yes. De-identified individual participant data for primary and secondary outcome measures will be available
Related trials for PCOS
Recruiting
Efficacy of Ovarian Drilling Via vNOTES Laparoscopy in Patients With PCOS
PCOS (Polycystic Ovary Syndrome)
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingObservational study
The Value of LC-MS/MS Detection of Androgen Profiles in the Diagnosis of PCOS: A Prospective, Multicenter Real-world Study
Polycystic Ovary Syndrome (PCOS)
Recruiting
The Effects of the Mediterranean Diet and Synbiotics in Polycystic Ovary Syndrome
PCOS (Polycystic Ovary Syndrome)
Recruiting
Brown Adipose Tissue Modulation in Polycystic Ovary Syndrome Using Infrared Thermography
Polycystic Ovary Syndrome (PCOS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reda MK Ghanem, Lecturer study director
Obstetrics & Gynecology department Faculty of medicine, Ain shams University.
Ahmed MN Hashaad, Professor study director
Obstetrics & Gynecology department - Faculty of medicine, Ain shams University.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vit D, Metformin and Clomiphene in people with PCOS and Vitamin D Deficiency, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Follicle growth and maturation (time frame: 11days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2019.