RA-2 13-cis Retinoic Acid (Isotretinoin)
Condition: Male Infertility; Klinefelter's Syndrome; Y-chromosome Microdeletions
MeSH terms: Infertility; Infertility, Male; Klinefelter Syndrome
Intervention: 13-cis retinoic acid; Calcitriol
Intervention description: Accutane is used for the treatment of severe acne; Calcitriol is a form of vitamin D given twice daily (BID)
Intervention MeSH terms: Calcitriol; Dihydroxycholecalciferols; Tretinoin; Isotretinoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: Male
Minimum age: 21 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Infertility

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.
    

Eligibility criteria:

        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