RA-2 13-cis Retinoic Acid (Isotretinoin)

Phase 2

Completed

• Conditions: Male Infertility; Klinefelter's Syndrome; Y-chromosome Microdeletions
• Interventions: Drug: 13-cis retinoic acid; Drug: Calcitriol

• Registration Number: NCT02061384
• Lead Sponsor: University of Washington

Brief Summary

Men with infertility and normal hormone levels have few options for fertility treatment. Previous research work has suggested that men with infertility may have low levels of the active form of Vitamin A, called retinoic acid, in their testes. We think that giving men with low sperm counts retinoic acid may increase their sperm counts and improve their chances of fathering a pregnancy. We want to see if retinoic acid administration over twenty weeks can increase sperm production and help infertile men become fathers without the need for In vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). We also want to see if adding calcitriol with retinoic acid will improve sperm motility in a sub-set of subjects.

Detailed Description

This is a 20 week, unblinded, two-arm pilot study to determine the impact of therapy with 13-cis retinoic acid and calcitriol on sperm indices in infertile men. Twenty infertile men, ages 21-60 with abnormal sperm analyses will be enrolled for 20-week and given 20 mg 13-cis retinoic acid, twice daily. Subjects#11-#20 will also be administered calcitriol to see if adding calcitriol with Accutane will improve sperm motility. All subjects will be closely followed for side effects related to treatment. The impact of treatment on indices of spermatogenesis will be determined by monthly seminal fluid analyses.

Study Timeline

• Study First Submitted: 2014-02-10
• Study First Submitted QC: 2014-02-10
• Study First Posted: 2014-02-12
• Study Start: 2014-08
• Primary Completion: 2018-12
• Study Completion: 2018-12
• Results First Submitted: 2021-04-26
• Status Verified: 2021-06
• Results First Submitted QC: 2021-07-09
• Last Update Submitted: 2021-07-29
• Results First Posted: 2021-07-30
• Last Update Posted: 2021-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

• Subjects will be infertile men (no pregnancy with partner with normal cycles and normal hysterosalpingogram despite >1 year of unprotected intercourse).
• Abnormal sperm analyses with a total, motile sperm count of less than 10 million sperm as assessed by semen analysis on two occasions separated by one week.
• In the opinion of the investigator, is able to comply with the protocol, understand and sign an informed consent and HIPAA (Health Insurance Portability and Accountability Act ) form.

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Exclusion Criteria

• Men participating in another clinical trial
• Men not living in the catchment area of the clinic
• Clinically significant abnormal findings at screening
• Known genetic infertility (e.g. Klinefelter syndrome or Y-chromosome microdeletions),
• Hypogonadotropic hypogonadism (that might respond to gonadotropin injections),
• The use of anabolic steroids, illicit drugs, or the consumption of more than 4 alcoholic beverages daily
• Severe mental health problems requiring medications
• Current therapy with retinoic acid (e.g. Accutane) or vitamin A.
• Score of greater than 15 on the Patient health questionnaire (PHQ9).
• Abnormal serum chemistry values according to local laboratory normal values which indicate liver or kidney dysfunction. Other abnormal lab values may also be exclusionary, at the discretion of the investigator
• Men with a personal history of serious psychiatric disorders
• Men currently receiving tetracycline containing medications
• Men currently receiving phenytoin
• Men with a history of inflammatory bowel disease
• Men with a history of bone disease
• Men who have used isotretinoin within eight weeks of the start of dosing
• Men with elevated serum triglycerides

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
13-cis retinoic acid	13-cis retinoic acid	20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks
Calcitriol 0.25 mcg	13-cis retinoic acid	oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks
Calcitriol 0.25 mcg	Calcitriol	oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks

Primary Outcome Measures

Name	Time	Method
Millions of Sperm Per Ejaculate	Up to 20-weeks	Millions of sperm per ejaculate in men treated with 13-cis retinoic acid

Trial Locations

Locations (1)

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