Primary Ovarian InsufficiencyPhase 1/2NCT01662466
Effect of Testosterone Treatment on Embryo Quality
A Phase 1/2 study testing Testosterone cream (0.5mg per gram) and DHEA in people with Primary Ovarian Insufficiency and Female Infertility Due to Diminished Ovarian Reserve, run by Center for Human Reproduction at 2 sites in United States.
Trial summary
The purpose of this study is to determine the effect of treatment with trans-dermal testosterone cream compared to placebo on measures of ovarian reserve, oocyte and embryo quality, and pregnancy rates among women with evidence of diminished ovarian reserve that have persistently low serum testosterone and free… Read more about this study
- Who is it for?
- Ages 38 to 44 years, women only
- Conditions the study is for
- Primary Ovarian Insufficiency, Female Infertility Due to Diminished Ovarian Reserve
- What is being tested?
- Testosterone cream (0.5mg per gram) and DHEA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jul 2012to 31 Dec 2022
- Phase
- Phase 1/2
- 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 38 to 44 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women with 38 to 44 years old planning to undergo ovulation induction for IVF who are willing to sign an informed consent.
- BMI > 18 and <= 30 kg/m^2
- FSH > 10 mIU/mL
- AMH =< 1.05 ng/mL
- Using DHEA for treatment of DOR/POA.
- Baseline Total Testosterone less than 30 ng per deciliter (1.0 nmol per liter) or serum free testosterone concentrations of less than 3.5 pg per milliliter (12.1 pmol per liter), which are below the median values for normal premenopausal women (Endocrine Sciences, Calabasas Hills, Calif.).
Who cannot join
- History of hormone dependent neoplasm
- History of severe acne or hirsutism.
- Hyperlipidemia.
- Pre existing cardiac, renal or hepatic disease
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 1 recruiting
- Recruiting
Center For Human Reproduction
New York, New York, 10021
Jolanta Tapper, 212-994-4400, jtapper@theCHR.com
David H Barad, MD MS
- Active, not recruiting
Department of Medicine; Division of Endocrinology and Metabolism, University of Rochester School of Medicine and Dentistry
Rochester, New York, 14642
About this study
Official title: A Randomized Double Blind Control Trial of Transdermal Testosterone Supplementation vs Placebo on Follicular Development and Atresia, Oocyte and Embryo Quality Among Women With Diminished Ovarian Reserve Undergoing in Vitro Fertilization
The purpose of this study is to determine the effect of treatment with trans-dermal testosterone cream compared to placebo on measures of ovarian reserve, oocyte and embryo quality, and pregnancy rates among women with evidence of diminished ovarian reserve that have persistently low serum testosterone and free testosterone after completing six previous weeks of DHEA supplementation.
Read the detailed description
At CHR the investigators have been using DHEA supplementation to improve ovarian response to ovulation induction for in vitro fertilization for about five years (Barad, Brill et al. 2007; Barad, Weghofer et al .2009; Gleicher, Ryan et al. 2009; Gleicher, Weghofer et al. 2010; Gleicher and Barad 2011). Our views on the effect of androgens on the follicular environment have recently been reviewed (Gleicher, Weghofer et al. 2011). A recent analysis of androgen metabolites of DHEA in our patients suggested that women who successfully respond to DHEA supplementation with increased egg production and clinical pregnancy had testosterone above the normal median values for reproductive age women. There also appears to be a cohort of women who did not respond to DHEA and who had very low serum testosterone. The investigators decided to investigate if supplementing those women with testosterone to the normal female range would improve ovarian function and possibly increase pregnancy rates.
Recruitment \& Experimental Plan
- A baseline blood draw following completion of 6 weeks of DHEA supplementation will determine eligibility for the study. The baseline blood determinations are part of the standard pre cycle screening at CHR for all patients.
- After signing informed consent subjects will be randomly assigned to either active testosterone cream treatment or placebo.
- Active treatment will consist of a testosterone delivery system that will deliver transdermal testosterone cream(0.5 mg per gram of cream.) The cream and placebo cream will be compounded by Metro Drugs (New York, NY) and dispensed in calibrated pump that will deliver one gram of cream per stroke. Transdermal absorption is about 10% so 2 grams (1.0 mg) per day applied to the skin will deliver about 100 ug per day. In preliminary analysis we have determined that a 2 gram dose of this preparation will raise total testosterone to our target range of between 50 and 100 ng/dL.
- The dose of testosterone cream will be 2 grams of cream per day applied to the left inner forearm. The study medication will continue to be applied for 6 weeks.
- All patients with evidence of diminished ovarian reserve in our practice are treated with DHEA. Thus, patients in this study will be receiving DHEA + testosterone or DHEA + Placebo. Patients who achieve a level of serum testosterone in the desired range using DHEA alone will not be eligible for this study.
- Being tested
- Testosterone cream (0.5mg per gram), DHEA, Placebo
- Keywords
- testosterone, DHEA, IVF, egg quality, pregnancy rates
- Medical subject headings
- Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone cream (0.5mg per gram)Drug
Also called Testosterone
Testosterone cream 2 gms per day applied transdermally to the left wrist to deliver 1.mg daily dose with estimated absorption of 100 ug per day testosterone
DHEADietary supplement
Also called Dehydroepiandrosterone
DHEA 25mg tid
PlaceboDrug
Also called Carrier cream without added testosterone
Carrier cream without added testosterone in the identical type of pump
| Study group | Role | What they receive |
|---|---|---|
| DHEA+Testosterone | Active comparator | These patients will be administered the testosterone cream along with standard DHEA supplements Receives: Drug: Testosterone cream (0.5mg per gram); Dietary Supplement: DHEA |
| DHEA+Placebo | Placebo comparator | These patients will receive the placebo cream along with her DHEA supplements. In other words, no testosterone will be administered. Receives: Dietary Supplement: DHEA; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical and Ongoing Pregnancy
Clinical pregnancy is defined as the presence of a viable gestational sac visible in the uterus 4 weeks after embryo transfer. Clinical ongoing pregnancy is defined as intrauterine pregnancy with evidence of an active fetal heart at 6 weeks after embryo transfer.
Measured: 8 weeks post treatment initiation
Secondary outcomes (2)
Measures of Atresia
- Follicular fluid will be collected separately for the first 5 follicles aspirated that are at least 18mm diameter for each patient.
- Granulosa cell counts will be performed on each follicle fluid. Granulosa cell counts of <10,000 per follicle will be considered atretic.
- Aliquots of follicular fluid will be analyzed for Testosterone, androstenedoine and estradiol using standard immuno assay. Healthy follicles should be capable of metabolizing testosterone to estradiol and should have a higher concentration estradiol (in nmol/ml) compared to testosterone
Measured: 8 weeks after intervention initiation
Oocytes number
The number of oocytes retrieved at oocyte retrieval for in-vitro fertilization will be compared between the treatment group and placebo.
Measured: 8 weeks after initiation of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2012 (estimated)
- Study start1 Jul 2012
- Primary completion1 Jun 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Ovarian InsufficiencyStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Center for Human Reproduction
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Reproductive Medicine
- Responsible party
- Sponsor
- Investigators
- Norbert Gleicher, MD, Study chair, Center for Human ReproductionDavid H Barad, MD, MS, Principal investigator, Center for Human Reproduction
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01662466
- Sponsor's protocol ID
- 072312-01
- Other IDs
- CHR-DHEA-testosterone-2012
- Status last verified
- Feb 2020
- First submitted
- 2 Aug 2012
- Last updated
- 12 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: We do not plan to share IPD
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blind Control Trial of Transdermal Testosterone Supplementation vs Placebo on Follicular Development and Atresia, Oocyte and Embryo Quality Among Women With Diminished Ovarian Reserve Undergoing in Vitro Fertilization
- ClinicalTrials.gov ID
- NCT01662466
- Acronym / sponsor ID
- 072312-01
- Keywords
- testosterone, DHEA, IVF, egg quality, pregnancy rates
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Center for Human ReproductionUniversity, hospital or other
- Collaborators
- Foundation for Reproductive Medicine
- Study start
- 1 Jul 2012
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 10 Aug 2012 (estimated)
- 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.
The purpose of this study is to determine the effect of treatment with trans-dermal testosterone cream compared to placebo on measures of ovarian reserve, oocyte and embryo quality, and pregnancy rates among women with evidence of diminished ovarian reserve that have persistently low serum testosterone and free testosterone after completing six previous weeks of DHEA supplementation.
Detailed description
At CHR the investigators have been using DHEA supplementation to improve ovarian response to ovulation induction for in vitro fertilization for about five years (Barad, Brill et al. 2007; Barad, Weghofer et al .2009; Gleicher, Ryan et al. 2009; Gleicher, Weghofer et al. 2010; Gleicher and Barad 2011). Our views on the effect of androgens on the follicular environment have recently been reviewed (Gleicher, Weghofer et al. 2011). A recent analysis of androgen metabolites of DHEA in our patients suggested that women who successfully respond to DHEA supplementation with increased egg production and clinical pregnancy had testosterone above the normal median values for reproductive age women. There also appears to be a cohort of women who did not respond to DHEA and who had very low serum testosterone. The investigators decided to investigate if supplementing those women with testosterone to the normal female range would improve ovarian function and possibly increase pregnancy rates.
Recruitment \& Experimental Plan
- A baseline blood draw following completion of 6 weeks of DHEA supplementation will determine eligibility for the study. The baseline blood determinations are part of the standard pre cycle screening at CHR for all patients.
- After signing informed consent subjects will be randomly assigned to either active testosterone cream treatment or placebo.
- Active treatment will consist of a testosterone delivery system that will deliver transdermal testosterone cream(0.5 mg per gram of cream.) The cream and placebo cream will be compounded by Metro Drugs (New York, NY) and dispensed in calibrated pump that will deliver one gram of cream per stroke. Transdermal absorption is about 10% so 2 grams (1.0 mg) per day applied to the skin will deliver about 100 ug per day. In preliminary analysis we have determined that a 2 gram dose of this preparation will raise total testosterone to our target range of between 50 and 100 ng/dL.
- The dose of testosterone cream will be 2 grams of cream per day applied to the left inner forearm. The study medication will continue to be applied for 6 weeks.
- All patients with evidence of diminished ovarian reserve in our practice are treated with DHEA. Thus, patients in this study will be receiving DHEA + testosterone or DHEA + Placebo. Patients who achieve a level of serum testosterone in the desired range using DHEA alone will not be eligible for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DHEA+Testosterone | Active comparator | Drug: Testosterone cream (0.5mg per gram), Dietary Supplement: DHEAThese patients will be administered the testosterone cream along with standard DHEA supplements |
| DHEA+Placebo | Placebo comparator | Dietary Supplement: DHEA, Drug: PlaceboThese patients will receive the placebo cream along with her DHEA supplements. In other words, no testosterone will be administered. |
Who may qualify
- Ages
- 38 to 44 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Women with 38 to 44 years old planning to undergo ovulation induction for IVF who are willing to sign an informed consent.
- BMI > 18 and <= 30 kg/m^2
- FSH > 10 mIU/mL
- AMH =< 1.05 ng/mL
- Using DHEA for treatment of DOR/POA.
Key exclusion criteria (4 listed)
- History of hormone dependent neoplasm
- History of severe acne or hirsutism.
- Hyperlipidemia.
- Pre existing cardiac, renal or hepatic disease
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 |
|---|---|---|
| Testosterone cream (0.5mg per gram)Also: TestosteroneTestosterone cream 2 gms per day applied transdermally to the left wrist to deliver 1.mg daily dose with estimated absorption of 100 ug per day testosterone | Drug | DHEA+Testosterone |
| DHEAAlso: DehydroepiandrosteroneDHEA 25mg tid | Dietary supplement | DHEA+Placebo, DHEA+Testosterone |
| PlaceboAlso: Carrier cream without added testosteroneCarrier cream without added testosterone in the identical type of pump | Drug | DHEA+Placebo |
Primary outcome
Clinical and Ongoing Pregnancy
Time frame: 8 weeks post treatment initiation
Clinical pregnancy is defined as the presence of a viable gestational sac visible in the uterus 4 weeks after embryo transfer. Clinical ongoing pregnancy is defined as intrauterine pregnancy with evidence of an active fetal heart at 6 weeks after embryo transfer.
2 secondary outcomes
Measures of Atresia
Time frame: 8 weeks after intervention initiation
Oocytes number
Time frame: 8 weeks after initiation of intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2020.
- Individual participant dataSharing planned: No. We do not plan to share IPD
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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.
Norbert Gleicher, MD study chair
Center for Human Reproduction
David H Barad, MD, MS principal investigator
Center for Human Reproduction
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Testosterone cream (0.5mg per gram) and DHEA in people with Primary Ovarian Insufficiency and Female Infertility Due to Diminished Ovarian Reserve, run by Center for Human Reproduction at 2 sites in United States.
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 6 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 12 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jolanta Tapper, MD MS (212 994-4400 ext. 4406, jtapper@theCHR.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical and Ongoing Pregnancy (time frame: 8 weeks post treatment initiation). 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 12 Nov 2020.