RA-2 13-cis Retinoic Acid (Isotretinoin)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot Trial of 13-cis Retinoic Acid (Isotretinoin) for the Treatment of Men With Oligoasthenoteratozoospermia

Conditions
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Male Infertility, Klinefelter's Syndrome, Y-chromosome Microdeletions

Intervention / Treatment
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* Drug: 13-cis retinoic acid
* Drug: Calcitriol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 13-cis retinoic acid<br>20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks | Drug: 13-cis retinoic acid<br>* Accutane is used for the treatment of severe acne<br>* Other names: Isotretinoin;|
| Experimental: Calcitriol 0.25 mcg<br>oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks | Drug: 13-cis retinoic acid<br>* Accutane is used for the treatment of severe acne<br>* Other names: Isotretinoin;Drug: Calcitriol<br>* Calcitriol is a form of vitamin D given twice daily (BID)<br>* Other names: 1,25-dihydroxyvitamin D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Millions of Sperm Per Ejaculate | Millions of sperm per ejaculate in men treated with 13-cis retinoic acid | Up to 20-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility