Back to resultsRA-2 13-cis Retinoic Acid (Isotretinoin) (RA-2)
Primary Purpose
Male Infertility, Klinefelter's Syndrome, Y-chromosome Microdeletions
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
13-cis retinoic acid
Calcitriol
Sponsored by
About this trial
This is an interventional treatment trial for Male Infertility focused on measuring Infertility
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
Sites / Locations
- University of Washington Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
13-cis retinoic acid
Calcitriol 0.25 mcg
Arm Description
20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks
oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks
Outcomes
Primary Outcome Measures
Millions of Sperm Per Ejaculate
Millions of sperm per ejaculate in men treated with 13-cis retinoic acid
Secondary Outcome Measures
Full Information
NCT ID
NCT02061384
First Posted
February 10, 2014
Last Updated
July 29, 2021
Sponsor
University of Washington
1. Study Identification
Unique Protocol Identification Number
NCT02061384
Brief Title
RA-2 13-cis Retinoic Acid (Isotretinoin)
Acronym
RA-2
Official Title
A Pilot Trial of 13-cis Retinoic Acid (Isotretinoin) for the Treatment of Men With Oligoasthenoteratozoospermia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Infertility, Klinefelter's Syndrome, Y-chromosome Microdeletions
Keywords
Infertility
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
13-cis retinoic acid
Arm Type
Experimental
Arm Description
20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks
Arm Title
Calcitriol 0.25 mcg
Arm Type
Experimental
Arm Description
oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks
Intervention Type
Drug
Intervention Name(s)
13-cis retinoic acid
Other Intervention Name(s)
Accutane, Isotretinoin
Intervention Description
Accutane is used for the treatment of severe acne
Intervention Type
Drug
Intervention Name(s)
Calcitriol
Other Intervention Name(s)
1,25-dihydroxyvitamin D3
Intervention Description
Calcitriol is a form of vitamin D given twice daily (BID)
Primary Outcome Measure Information:
Title
Millions of Sperm Per Ejaculate
Description
Millions of sperm per ejaculate in men treated with 13-cis retinoic acid
Time Frame
Up to 20-weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John K Amory, MD, MPH
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
12. IPD Sharing Statement
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RA-2 13-cis Retinoic Acid (Isotretinoin)
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