Clinical trial NCT03323801: RA-4: 13-cis Retinoic Acid for Treatment of Men With Azoospermia
Official title: A Pilot Trial of 13-cis Retinoic Acid (Isotretinoin) for the Treatment of Men With Azoospermia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Male Infertility, Azoospermia
Keywords: Infertility
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2017-10-27
Enrollment: 10
Sex: MALE
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 20 mg 13-cis retinoic acid twice daily (BID) with meals for 32 weeks
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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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

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Primary outcomes:
measure: Total Motile Sperm
timeFrame: up to 32 weeks
measure: Total Sperm and Percentage of These Sperm That Were Motile
timeFrame: 32 weeks
Secondary outcomes:
measure: Serious and Non-Serious Adverse Effects
timeFrame: 32 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: John K Amory, MD
role: PRINCIPAL_INVESTIGATOR
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