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

Sponsor

Center for Human Reproduction (Other)

Overall Status

Terminated

CT.gov ID

NCT00650754

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Primary Ovarian Insufficiency Unexplained Infertility	Dietary Supplement: Dehydroepiandrosterone Other: Placebo	Phase 2/Phase 3

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:

Informed consent
Baseline studies

Antral follicle counts on Day 2 - 3 of cycle
Day 3 Serum FSH, LH, E2, Prog, DHEA, DHEAS, testosterone, AMH, Fragile X

Randomization for pretreatment

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

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

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 Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized Double Blinded Trail of DHEA Supplementation for Treatment of Couples With Normal Hysterosalpingogram and Normal Semen Analysis and Evidence of Premature Ovarian Aging (POA).

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DHEA 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.	Dietary Supplement: Dehydroepiandrosterone 25 mg PO TID Other Names: DHEA
Placebo Comparator: Placebo Blinded placebo	Other: Placebo Placebo

Arm

Intervention/Treatment

Experimental: DHEA

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.

Dietary Supplement: Dehydroepiandrosterone

25 mg PO TID

Other Names:

DHEA

Placebo Comparator: Placebo

Blinded placebo

Other: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Live Birth [24 months]

Secondary Outcome Measures

Endocrine effects [12 months]
Androgen side effects [12 months]
Clinical Pregnancy [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 37 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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