Study of Oral Dehydroepiandrosterone(DHEA) to Treat Previously Unexplained Infertility

Phase 2

Terminated

• Conditions: Primary Ovarian Insufficiency; Unexplained Infertility
• Interventions: Other: Placebo; Dietary Supplement: Dehydroepiandrosterone

• Registration Number: NCT00650754
• Lead Sponsor: Center for Human Reproduction

Brief Summary

The experimental focus of this project is on the interaction of DHEA treatment on pregnancy in women with otherwise unexplained infertility and evidence of premature ovarian aging (POA).

Detailed Description

Recruitment:

Eligible patients will be recruited by advertising on the web and in newspaper. We will screen women under 38 years old with regular menstrual cycles and more than one year of infertility.

Experimental plan:

1. Informed consent

2. Baseline studies

* Antral follicle counts on Day 2 - 3 of cycle

* Day 3 Serum FSH, LH, E2, Prog, DHEA, DHEAS, testosterone, AMH, Fragile X

3. Randomization for pretreatment

* Group A: DHEA (25 mg three times per day)

* Group B: Placebo

4. Monitoring during treatment

* All participants will have:

* USG for follicle measurement

* Repeat serum, FSH, E2, DHEA, DHEAS, testosterone, AMH monthly during treatment.

* Physical examination

* Completion of study questionnaire regarding possible androgen effects of treatment

5. Analysis plan:

* Primary Outcome

* Pregnancy

* Pregnancy rates will be compared using logistic regression with age and pre-treatment AMH as covariates.

* Secondary Outcomes

* Endocrine Factors

* Androgen side effects

* Primary analysis. We will perform a factorial ANOVA for the two pretreatment factors DHEA and Placebo. Baseline AMH and age as main covariates

* Secondary analysis.

* Examine rate of change of estradiol and other endocrine response over the four cycles of pretreatment

* Compare antral follicle counts across pretreatment cycles between groups

* Compare possible androgen related effects

* Power considerations:

* Power assumptions: alpha 0.05; 80% power

* Pregnancy rate for unexplained infertility is 2% per cycle.

* Intervention will improve pregnancy rate to 5% per cycle.

* Patients will be treated for 8 cycles.

* Cumulative pregnancy rate for control patients - 13%

* Cumulative pregnancy rate for Treated patients - 30%

* Require 91 patients to complete treatment in each group.

* Allow for 20% dropout ( 91\* 1.2) will need 109 patients randomized to each group.

* Randomization:

Randomization will be by permuted blocks in order to maintain an even distribution among the groups (because of the small numbers of participants)

* Human subjects issues

* Potential risks associated with DHEA use

* Potential risk of delay of treatment for 8 months and possible natural continued loss of fertility

* Informed consent issues

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2008-03-31
• Study First Submitted QC: 2008-04-01
• Study First Posted: 2008-04-02
• Primary Completion: 2014-03
• Study Completion: 2014-03
• Status Verified: 2015-09
• Last Update Submitted: 2015-09-28
• Last Update Posted: 2015-09-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 35

Inclusion Criteria

• >= 1 year of infertility
• < 38 years old
• Normal HSG
• Normal Semen analysis (Count >= 20 million/ motility > 50%/ Kruger morph > 14%.
• Regular menses
• Willingness to sign informed consent for study randomization
• Willingness to participate in 8 months of non-IVF will he him treatment.

Exclusion Criteria

• Abnormal semen analysis
• Abnormal HSG
• Baseline FSH/E2 within normal age specific criteria
• Medical condition that would contraindicate pregnancy, ovulation induction or general anesthesia
• Family history of significant genetic disease, or factor V leiden thrombophilia
• Inability to present for monitoring visits
• Inability to follow medication instruction
• Desire to undergo other fertility treatments before completing eight months of this trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Blinded placebo
DHEA	Dehydroepiandrosterone	Dehydroepiandrosterone (DHEA) administered at a dose of 25 mg tid po. DHEA is a weak androgen produced naturally by the adrenal in men and women. DHEA production is diminished with increasing age. Peak levels of DHEA occur in the late teenage years.

Primary Outcome Measures

Name	Time	Method
Live Birth	24 months

Secondary Outcome Measures

Name	Time	Method
Androgen side effects	12 months
Endocrine effects	12 months
Clinical Pregnancy	12 months

Trial Locations

Locations (1)

Center for Human Reproduction; 🇺🇸 New York, New York, United States