This trial is active, not recruiting.

Conditions male infertility, klinefelter's syndrome, y-chromosome microdeletions
Treatments 13-cis retinoic acid, calcitriol
Phase phase 2
Sponsor University of Washington
Start date August 2014
End date December 2017
Trial size 20 participants
Trial identifier NCT02061384, 46478-A


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks
13-cis retinoic acid Accutane
Accutane is used for the treatment of severe acne
oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks
calcitriol 1,25-dihydroxyvitamin D3
Calcitriol is a form of vitamin D given twice daily (BID)

Primary Outcomes

Total motile sperm
time frame: Up to 20-weeks

Secondary Outcomes

13-cis retinoic acid serum level
time frame: 20-weeks
Number of Participants with Serious and Non-Serious Adverse effects associated with treatment with 13-cis retinoic acid
time frame: 20-weeks
13-cis retinoic acid Seminal Plasma Concentration
time frame: Up to 20-weeks
To determine if the additions of calcitriol with 13-cis retinoic acid can improve sperm motility
time frame: 20 weeks

Eligibility Criteria

Male participants from 21 years up to 60 years old.

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. 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

Additional Information

Official title A Pilot Trial of 13-cis Retinoic Acid (Isotretinoin) for the Treatment of Men With Oligoasthenoteratozoospermia
Principal investigator John K Amory, MD, MPH
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by University of Washington.