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RA-2 13-cis Retinoic Acid (Isotretinoin) (RA-2)

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ClinicalTrials.gov Identifier: NCT02061384
Recruitment Status : Active, not recruiting
First Posted : February 12, 2014
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
John Amory, University of Washington

Study Description
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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.

Condition or disease Intervention/treatment Phase
Male Infertility Klinefelter's Syndrome Y-chromosome Microdeletions Drug: 13-cis retinoic acid Drug: Calcitriol Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Trial of 13-cis Retinoic Acid (Isotretinoin) for the Treatment of Men With Oligoasthenoteratozoospermia
Study Start Date : August 2014
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: 13-cis retinoic acid
20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks
 Drug: 13-cis retinoic acid
Accutane is used for the treatment of severe acne
Other Names:
  • Accutane
  • Isotretinoin
Experimental: Calcitriol 0.25 mcg
oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks
 Drug: Calcitriol
Calcitriol is a form of vitamin D given twice daily (BID)
Other Name: 1,25-dihydroxyvitamin D3


Outcome Measures
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Primary Outcome Measures :
  1. Total motile sperm [ Time Frame: Up to 20-weeks ]
    Total motile sperm count in men treated with 13-cis retinoic acid


Secondary Outcome Measures :
  1. 13-cis retinoic acid serum level [ Time Frame: 20-weeks ]
    Concentration level of 13-cis retinoic acid in the serum of treated men

  2. Number of Participants with Serious and Non-Serious Adverse effects associated with treatment with 13-cis retinoic acid [ Time Frame: 20-weeks ]
    Number of adverse effects per subject associated with treatment with 13-cis retinoic acid

  3. 13-cis retinoic acid Seminal Plasma Concentration [ Time Frame: Up to 20-weeks ]
    13-cis retinoic acid concentration in semen of treated men

  4. To determine if the additions of calcitriol with 13-cis retinoic acid can improve sperm motility [ Time Frame: 20 weeks ]
    improved sperm motility


Eligibility Criteria
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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02061384


Locations
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: John K Amory, MD, MPH University of Washington
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:
Center for Disease Control. Infertility Facts,m accessed at http://www.ede.gov/nchs/fastats/fertile.htm (June 3, 2013)

Responsible Party: John Amory, Professor, General Internal Medicine, University of Washington
ClinicalTrials.gov Identifier: NCT02061384     History of Changes
Other Study ID Numbers: STUDY00000564
First Posted: February 12, 2014    Key Record Dates
Last Update Posted: May 30, 2017
Last Verified: May 2017

Keywords provided by John Amory, University of Washington:
Infertility

Additional relevant MeSH terms:
Klinefelter Syndrome
Infertility
Infertility, Male
Chromosome Deletion
Sex Chromosome Aberrations
Sex Chromosome Disorders of Sex Development
Genital Diseases, Male
Genital Diseases, Female
Disorders of Sex Development
Urogenital Abnormalities
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Gonadal Disorders
 Endocrine System Diseases
Hypogonadism
Monosomy
Aneuploidy
Chromosome Aberrations
Pathologic Processes
Calcitriol
Dihydroxycholecalciferols
Tretinoin
Isotretinoin
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Vitamins