RA-2 13-cis Retinoic Acid (Isotretinoin)

NCT ID: NCT02061384

Last Updated: 2021-08-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-31

Study Completion Date

2018-12-31

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.

Conditions

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Male Infertility Klinefelter's Syndrome Y-chromosome Microdeletions

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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13-cis retinoic acid

20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks

Group Type EXPERIMENTAL

13-cis retinoic acid

Intervention Type DRUG

Accutane is used for the treatment of severe acne

Calcitriol 0.25 mcg

oral calcitriol 025 mcg BID subjects 11-20 for 20 weeks

Group Type EXPERIMENTAL

13-cis retinoic acid

Intervention Type DRUG

Accutane is used for the treatment of severe acne

Calcitriol

Intervention Type DRUG

Calcitriol is a form of vitamin D given twice daily (BID)

Interventions

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13-cis retinoic acid

Accutane is used for the treatment of severe acne

Intervention Type DRUG

Calcitriol

Calcitriol is a form of vitamin D given twice daily (BID)

Intervention Type DRUG

Other Intervention Names

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Accutane Isotretinoin 1,25-dihydroxyvitamin D3

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
Minimum Eligible Age

21 Years

Maximum Eligible Age

60 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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University of Washington

OTHER

Sponsor Role lead

Responsible Party

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John Amory

Professor, General Internal Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John K Amory, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

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University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Schlegel PN. Nonobstructive azoospermia: a revolutionary surgical approach and results. Semin Reprod Med. 2009 Mar;27(2):165-70. doi: 10.1055/s-0029-1202305. Epub 2009 Feb 26.

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

Reference Type BACKGROUND

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Chung SS, Wang X, Wolgemuth DJ. Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis. Development. 2009 Jun;136(12):2091-100. doi: 10.1242/dev.020040.

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PMID: 8388780 (View on PubMed)

Lufkin T, Lohnes D, Mark M, Dierich A, Gorry P, Gaub MP, LeMeur M, Chambon P. High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7225-9. doi: 10.1073/pnas.90.15.7225.

Reference Type BACKGROUND
PMID: 8394014 (View on PubMed)

Kastner P, Mark M, Leid M, Gansmuller A, Chin W, Grondona JM, Decimo D, Krezel W, Dierich A, Chambon P. Abnormal spermatogenesis in RXR beta mutant mice. Genes Dev. 1996 Jan 1;10(1):80-92. doi: 10.1101/gad.10.1.80.

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Ghyselinck NB, Vernet N, Dennefeld C, Giese N, Nau H, Chambon P, Viville S, Mark M. Retinoids and spermatogenesis: lessons from mutant mice lacking the plasma retinol binding protein. Dev Dyn. 2006 Jun;235(6):1608-22. doi: 10.1002/dvdy.20795.

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Hoting VE, Schutte B, Schirren C. [Isotretinoin treatment of acne conglobata. Andrologic follow-up]. Fortschr Med. 1992 Aug 20;110(23):427-30. German.

Reference Type BACKGROUND
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PMID: 3159708 (View on PubMed)

Torok L, Kadar L, Kasa M. Spermatological investigations in patients treated with etretinate and isotretinoin. Andrologia. 1987 Nov-Dec;19(6):629-33. doi: 10.1111/j.1439-0272.1987.tb01915.x.

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Nya-Ngatchou JJ, Arnold SL, Walsh TJ, Muller CH, Page ST, Isoherranen N, Amory JK. Intratesticular 13-cis retinoic acid is lower in men with abnormal semen analyses: a pilot study. Andrology. 2013 Mar;1(2):325-31. doi: 10.1111/j.2047-2927.2012.00033.x. Epub 2012 Nov 29.

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PMID: 23413144 (View on PubMed)

WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction

Reference Type BACKGROUND

Christiansen C, Christensen MS, Rodbro P, Hagen C, Transbol I. Effect of 1,25-dihydroxy-vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis. Eur J Clin Invest. 1981 Aug;11(4):305-9. doi: 10.1111/j.1365-2362.1981.tb02121.x.

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Gallagher JC, Fowler SE, Detter JR, Sherman SS. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab. 2001 Aug;86(8):3618-28. doi: 10.1210/jcem.86.8.7703.

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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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STUDY00000564

Identifier Type: -

Identifier Source: org_study_id

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