RA-4: 13-cis Retinoic Acid for Treatment of Men With Azoospermia

Phase 2

Completed

• Conditions: Male Infertility, Azoospermia
• Interventions: Drug: 13-cis retinoic acid

• Registration Number: NCT03323801
• Lead Sponsor: University of Washington

Brief Summary

Men with infertility and normal hormone levels have few options for fertility treatment. Previous research suggests that men with infertility may have low levels of the active form of Vitamin A, called retinoic acid, in their testes. In a pilot study of 20 men with low numbers of sperm (\<10 million motile sperm), roughly half the men showed improvement in sperm production. Thus, we want to see if retinoic acid administration to men with azoospermia (no sperm present) can initiate sperm production.

Detailed Description

Twenty men with infertility, aged 21 - 60, due to azoospermia (no apparent sperm in the ejaculate on two separate occasions) will be enrolled in a single-arm pilot trial of daily oral therapy of 20 mg twice daily of 13-cis retinoic acid for 32 weeks. The impact of treatment on the appearance of sperm in the ejaculate will be determined by monthly semen analyses.

Note: The outcome measure of serum and seminal plasma 13-cis-retinoic acid concentrations was entered in error and not intended to be reported for this study. Information on these levels is available in our earlier study of 13-cis-retinoic acid in men with sub-fertility. Amory et al. Andrology 2017 5:1115-1123.

Study Timeline

• Study Start: 2017-07-25
• Study First Submitted: 2017-10-24
• Study First Submitted QC: 2017-10-24
• Study First Posted: 2017-10-27
• Primary Completion: 2019-05-16
• Study Completion: 2019-05-31
• Results First Submitted: 2021-04-26
• Status Verified: 2021-09
• Results First Submitted QC: 2021-09-27
• Last Update Submitted: 2021-09-27
• Results First Posted: 2021-10-26
• Last Update Posted: 2021-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

Inclusion Criteria

Infertile men with azoospermia on at least two semen analyses separated by at least one week, and no pregnancy with partner with normal cycles and normal hysterosalpingogram despite >1 year of unprotected intercourse.

Exclusion Criteria

hypogonadotropic hypogonadism (that might respond to gonadotropin injections); use of anabolic steroids,illicit drugs, or consumption of more than 4 alcoholic beverages daily; current therapy with retinoic acid (eg Accutane) or vitamin A- of use of isotretinoin within eight weeks of start of dosing;phenytoin, or medication containing tetracycline; personal history of serious psychiatric disorders, score of greater than 15 on the PHQ9 (mood) questionnaire; elevated serum serum triglycerides or other abnormal serum chemistry values; history of inflammatory bowel disease or bone disease; not living within catchment area; participation in another clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
13-cis retinoic acid	13-cis retinoic acid	20 mg 13-cis retinoic acid twice daily (BID) with means for 32 weeks

Primary Outcome Measures

Name	Time	Method
Total Sperm and Percentage of These Sperm That Were Motile	32 weeks	Number of total sperm in ejaculate and percentage of these sperm that were motile
Total Motile Sperm	up to 32 weeks	Number of participants with undetectable or detectable sperm in their ejaculates.

Secondary Outcome Measures

Name	Time	Method
Serious and Non-Serious Adverse Effects	32 weeks	Number of participants with Serious and Non-Serious Adverse effects associated with treatment with 13-cis retinoic acid

Trial Locations

Locations (1)

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States