Female InfertilityPhase 1NCT03755037
Clomiphene Citrate, Estradiol and Sildenafil for Induction of Ovulation in Unexplained Infertility
A Phase 1 study testing Clomid, Respatio and Ethinyl estradiol in people with Female Infertility, run by Nesreen Abdel Fattah Abdullah Shehata at 1 site in Egypt.
Trial summary
Diagnosis of unexplained infertility is made after the recommended testing fails to reveal any abnormality. The treatment for unexplained infertility is empiric because it does not address a specific defect or functional impairment. Read more about this study
- Who is it for?
- Ages 20 to 30 years, women only
- Conditions the study is for
- Female Infertility
- What is being tested?
- Clomid, Respatio and Ethinyl estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteEgypt
- Study dates
- 31 Jan 2017to 30 Apr 2018
- Phase
- Phase 1
- 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 30 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women whose infertility tests were normal then diagnosed as unexplained infertility.
Who cannot join
- Any cause of infertility male factor, tubal or ovarian.
- Chronic illness as cardiac or renal disease
- Any contraindication for used drugs
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clomiphine Citrate and Estradiol Versus Clomiphine Citrate and Sildenafil in Comparison With Clomiphine Citrate Alone for Induction of Ovulation in Unexplained Infertility: Double Blind Randomised Trial
Diagnosis of unexplained infertility is made after the recommended testing fails to reveal any abnormality. The treatment for unexplained infertility is empiric because it does not address a specific defect or functional impairment. The principal treatments for unexplained infertility include expectant observation with timed intercourse and lifestyle changes, clomiphene citrate and intrauterine insemination (IUI), controlled ovarian hyperstimulation (COH) with IUI, and IVF).
Read the detailed description
Clomiphene citrate has been widely used alone, and in combination with intrauterine insemination (IUI), for treatment of unexplained subfertility, The mechanism of action is based on its mixed estrogenic and antiestrogenic properties. Clomiphene is frequently used to treat unexplained female infertility by inducing multifollicular response and correcting potential subtle ovulatory dysfunction .,)The American Society for Reproductive Medicine,2003).
The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase, a periimplantation stage., )The American College of Obstetricians and Gynecologists,1995).
Although ovulation is found in 80% of women with a cumulative effect in 6-8 months, the pregnancy rate can still be very low in these women . The possible causes are the anti-estrogenic effects of CC at the endometrium and cervical mucus level . The endometrial effect is without doubt one of the most important handicaps in infertility treatment. The pregnancy rate can be very low, especially if the endometrial thickness (ET) is <6-8 mm ., )J Turk Ger Gynecol Assoc. ,2012).
Ethinyl E2 reverse the deleterious effect of CC on endometrial development during the follicular phase. Endometrial thickness was dependent on peak E2 concentrations in serum.,(Richard P. Dickey, et.al.,2003).
Sildenafil citrate could lead to an improvement in uterine blood flow and, in conjunction with estrogen, led to the estrogen-induced proliferation of the endometrial lining .
Sildenafil citrate enhances uterine blood flow and increases endometrial thickening . The achieved implantation depends on the blastocyst's ability to infiltrate the endometrium and develop a sustaining blood supply, which requires the following genes to produce the necessary proteins for digesting the endometrial cellular matrix, to regulate cell growth, and to induce angiogenesis (Razieh Dehghani Firouzabadi,et.al.,2013).
- Conditions
- Female Infertility
- Being tested
- Clomid, Respatio and Ethinyl estradiol
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clomid, Respatio and Ethinyl estradiolDrug
Drugs were received during the menstrual cycle.
| Study group | Role | What they receive |
|---|---|---|
| Estradiol and cc | Active comparator | Group 1 received estradiol, cc and placebo simillar to sildenafil for induction of ovulation.
CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient then ethinyl estradiol 0.05mg orally twice daily on the 8th day of same cycle till 11th day. Receives: Drug: Clomid, Respatio and Ethinyl estradiol |
| Sildenafil and cc | Active comparator | Group 2 received CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient, sildenafil citrate (Respatio) 20 mg tab orally 3 times daily from8th day of same cycle till 11th day and placebo simillar to estradiol. Receives: Drug: Clomid, Respatio and Ethinyl estradiol |
| Placebo and cc | Placebo comparator | Group 3 received cc and placebo similar to sildenafil and placebo similar to estradiol with the same doses. Receives: Drug: Clomid, Respatio and Ethinyl estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ultrasound parameters
Number of follicles in each ovary and endometrial thickness
Measured: at day 14 until day 17 of menstrual cycle
Secondary outcomes (1)
Pregnancy
A serum pregnancy test was done
Measured: at day 21 and 24 of menstrual cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2018
- Study start31 Jan 2017
- Primary completion30 Apr 2018
- Study completion30 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Female InfertilityStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Women with unexplained infertility (n=150) were divided into 3 equal groups. Group 1 received estradiol and clomiphine citrate (cc), group 2 received sildenafil and cc and group 3 cc and placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nesreen Abdel Fattah Abdullah Shehata
- Sponsor type
- University, hospital or other
- Collaborators
- Beni-Suef University
- Responsible party
- Sponsor-investigator, Nesreen Abdel Fattah Abdullah Shehata, Beni-Suef University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03755037
- Sponsor's protocol ID
- Beni-Suef 16
- Status last verified
- Nov 2018
- First submitted
- 25 Nov 2018
- Last updated
- 27 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
1. Alexander Quaas, MD, Ph .D .,and Anuja Dokras, MD . diagnosis and treatment of unexplainrd infertilityRev Obstet Gynecol. 2008 Spring; 1(2): 69-76 2. J Turk Ger Gynecol Assoc.: The effect of administering estrogen to clomiphene citrate stimulated cycles on endometrial thickness and pregnancy rates in unexplained infertility. (2012) . Sep 1;13(3):157-61. 3. Paulus WE, Strehler E, Zhang M, Jelinkova L,El-Danasouri I and Sterzik K. : Benefit of sildenafil citrate in assisted reproductivetherapy. Fertil Steri 2002 Apr;77(4):846-7. 4. Razieh Dehghani Firouzabadi, M.D., Robab Davar, M.D., Farzaneh Hojjat, M.D., and Mohamad Mahdavi, M.D. :effect of sildenafil on endomeerial preparation and outcome of frozen_thawed embryo transfer cycles(. Iran J Reprod Med. 2013 Feb; 11(2): 151-158. 5. Richard P. Dickey, M.D., Ph.D.,):clomiphene citrate for woman with unexplained infertility . pp 261-271 13 May 2015 6. The American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women:. Fertil Steril . Fertil Steril. 2013 Aug;100(2):341-8. doi: 10.1016/j.fertnstert.2013.05.033. Epub 2013 Jun 27.
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clomiphine Citrate and Estradiol Versus Clomiphine Citrate and Sildenafil in Comparison With Clomiphine Citrate Alone for Induction of Ovulation in Unexplained Infertility: Double Blind Randomised Trial
- ClinicalTrials.gov ID
- NCT03755037
- Acronym / sponsor ID
- Beni-Suef 16
- Conditions
- Female Infertility
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Nesreen Abdel Fattah Abdullah ShehataUniversity, hospital or other
- Collaborators
- Beni-Suef University
- Study start
- 31 Jan 2017 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 27 Nov 2018 (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.
Diagnosis of unexplained infertility is made after the recommended testing fails to reveal any abnormality. The treatment for unexplained infertility is empiric because it does not address a specific defect or functional impairment. The principal treatments for unexplained infertility include expectant observation with timed intercourse and lifestyle changes, clomiphene citrate and intrauterine insemination (IUI), controlled ovarian hyperstimulation (COH) with IUI, and IVF).
Detailed description
Clomiphene citrate has been widely used alone, and in combination with intrauterine insemination (IUI), for treatment of unexplained subfertility, The mechanism of action is based on its mixed estrogenic and antiestrogenic properties. Clomiphene is frequently used to treat unexplained female infertility by inducing multifollicular response and correcting potential subtle ovulatory dysfunction .,)The American Society for Reproductive Medicine,2003).
The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase, a periimplantation stage., )The American College of Obstetricians and Gynecologists,1995).
Although ovulation is found in 80% of women with a cumulative effect in 6-8 months, the pregnancy rate can still be very low in these women . The possible causes are the anti-estrogenic effects of CC at the endometrium and cervical mucus level . The endometrial effect is without doubt one of the most important handicaps in infertility treatment. The pregnancy rate can be very low, especially if the endometrial thickness (ET) is <6-8 mm ., )J Turk Ger Gynecol Assoc. ,2012).
Ethinyl E2 reverse the deleterious effect of CC on endometrial development during the follicular phase. Endometrial thickness was dependent on peak E2 concentrations in serum.,(Richard P. Dickey, et.al.,2003).
Sildenafil citrate could lead to an improvement in uterine blood flow and, in conjunction with estrogen, led to the estrogen-induced proliferation of the endometrial lining .
Sildenafil citrate enhances uterine blood flow and increases endometrial thickening . The achieved implantation depends on the blastocyst's ability to infiltrate the endometrium and develop a sustaining blood supply, which requires the following genes to produce the necessary proteins for digesting the endometrial cellular matrix, to regulate cell growth, and to induce angiogenesis (Razieh Dehghani Firouzabadi,et.al.,2013).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Women with unexplained infertility (n=150) were divided into 3 equal groups. Group 1 received estradiol and clomiphine citrate (cc), group 2 received sildenafil and cc and group 3 cc and placebo.
| Arm | Type | Receives |
|---|---|---|
| Estradiol and cc | Active comparator | Drug: Clomid, Respatio and Ethinyl estradiolGroup 1 received estradiol, cc and placebo simillar to sildenafil for induction of ovulation. CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient then ethinyl estradiol 0.05mg orally twice daily on the 8th day of same cycle till 11th day. |
| Sildenafil and cc | Active comparator | Drug: Clomid, Respatio and Ethinyl estradiolGroup 2 received CC 50 mg (clomid) orally twice daily from 3rd day to 7th day of menstrual cycle of the patient, sildenafil citrate (Respatio) 20 mg tab orally 3 times daily from8th day of same cycle till 11th day and placebo simillar to estradiol. |
| Placebo and cc | Placebo comparator | Drug: Clomid, Respatio and Ethinyl estradiolGroup 3 received cc and placebo similar to sildenafil and placebo similar to estradiol with the same doses. |
Who may qualify
- Ages
- 20 to 30 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Women whose infertility tests were normal then diagnosed as unexplained infertility.
Key exclusion criteria (3 listed)
- Any cause of infertility male factor, tubal or ovarian.
- Chronic illness as cardiac or renal disease
- Any contraindication for used drugs
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 |
|---|---|---|
| Clomid, Respatio and Ethinyl estradiolDrugs were received during the menstrual cycle. | Drug | Estradiol and cc, Placebo and cc, Sildenafil and cc |
Primary outcome
Ultrasound parameters
Time frame: at day 14 until day 17 of menstrual cycle
Number of follicles in each ovary and endometrial thickness
1 secondary outcome
Pregnancy
Time frame: at day 21 and 24 of menstrual cycle
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 27 Nov 2018.
- Background1. Alexander Quaas, MD, Ph .D .,and Anuja Dokras, MD . diagnosis and treatment of unexplainrd infertilityRev Obstet Gynecol. 2008 Spring; 1(2): 69-76 2. J Turk Ger Gynecol Assoc.: The effect of administering estrogen to clomiphene citrate stimulated cycles on endometrial thickness and pregnancy rates in unexplained infertility. (2012) . Sep 1;13(3):157-61. 3. Paulus WE, Strehler E, Zhang M, Jelinkova L,El-Danasouri I and Sterzik K. : Benefit of sildenafil citrate in assisted reproductivetherapy. Fertil Steri 2002 Apr;77(4):846-7. 4. Razieh Dehghani Firouzabadi, M.D., Robab Davar, M.D., Farzaneh Hojjat, M.D., and Mohamad Mahdavi, M.D. :effect of sildenafil on endomeerial preparation and outcome of frozen_thawed embryo transfer cycles(. Iran J Reprod Med. 2013 Feb; 11(2): 151-158. 5. Richard P. Dickey, M.D., Ph.D.,):clomiphene citrate for woman with unexplained infertility . pp 261-271 13 May 2015 6. The American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women:. Fertil Steril . Fertil Steril. 2013 Aug;100(2):341-8. doi: 10.1016/j.fertnstert.2013.05.033. Epub 2013 Jun 27.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clomid, Respatio and Ethinyl estradiol in people with Female Infertility, run by Nesreen Abdel Fattah Abdullah Shehata 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 1 inclusion and 3 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 27 Nov 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Ultrasound parameters (time frame: at day 14 until day 17 of menstrual cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03755037, which also lists 1 linked publication.
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 27 Nov 2018.