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RA-4: 13-cis Retinoic Acid for Treatment of Men With Azoospermia

NCT ID: NCT03323801

Last Updated: 2021-10-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-25

Study Completion Date

2019-05-31

Brief Summary

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Men with infertility and normal hormone levels have few options for fertility treatment. Previous research suggests that men with infertility may have low levels of the active form of Vitamin A, called retinoic acid, in their testes. In a pilot study of 20 men with low numbers of sperm (\<10 million motile sperm), roughly half the men showed improvement in sperm production. Thus, we want to see if retinoic acid administration to men with azoospermia (no sperm present) can initiate sperm production.

Detailed Description

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Twenty men with infertility, aged 21 - 60, due to azoospermia (no apparent sperm in the ejaculate on two separate occasions) will be enrolled in a single-arm pilot trial of daily oral therapy of 20 mg twice daily of 13-cis retinoic acid for 32 weeks. The impact of treatment on the appearance of sperm in the ejaculate will be determined by monthly semen analyses.

Note: The outcome measure of serum and seminal plasma 13-cis-retinoic acid concentrations was entered in error and not intended to be reported for this study. Information on these levels is available in our earlier study of 13-cis-retinoic acid in men with sub-fertility. Amory et al. Andrology 2017 5:1115-1123.

Conditions

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Male Infertility, Azoospermia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

20 mg 13-cis retinoic acid twice daily (BID) with meals for 32 weeks
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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13-cis retinoic acid

20 mg 13-cis retinoic acid twice daily (BID) with means for 32 weeks

Group Type EXPERIMENTAL

13-cis retinoic acid

Intervention Type DRUG

Accutane is used for the treatment of severe acne

Interventions

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13-cis retinoic acid

Accutane is used for the treatment of severe acne

Intervention Type DRUG

Other Intervention Names

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Accutane, Isotretinoin

Eligibility Criteria

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Inclusion Criteria

\-

Exclusion Criteria

\-
Minimum Eligible Age

21 Years

Maximum Eligible Age

60 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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John Amory

Professor, School of Medicine, General Internal Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John K Amory, MD

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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Jequier AM, Holmes SC. Primary testicular disease presenting as azoospermia or oligozoospermia in an infertility clinic. Br J Urol. 1993 Jun;71(6):731-5. doi: 10.1111/j.1464-410x.1993.tb16075.x.

Reference Type BACKGROUND
PMID: 8102079 (View on PubMed)

de Kretser DM. Male infertility. Lancet. 1997 Mar 15;349(9054):787-90. doi: 10.1016/s0140-6736(96)08341-9. No abstract available.

Reference Type BACKGROUND
PMID: 9074589 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19247918 (View on PubMed)

Napoli JL. Retinoic acid: its biosynthesis and metabolism. Prog Nucleic Acid Res Mol Biol. 1999;63:139-88. doi: 10.1016/s0079-6603(08)60722-9.

Reference Type BACKGROUND
PMID: 10506831 (View on PubMed)

Doyle TJ, Braun KW, McLean DJ, Wright RW, Griswold MD, Kim KH. Potential functions of retinoic acid receptor A in Sertoli cells and germ cells during spermatogenesis. Ann N Y Acad Sci. 2007 Dec;1120:114-30. doi: 10.1196/annals.1411.008. Epub 2007 Sep 28.

Reference Type BACKGROUND
PMID: 17905941 (View on PubMed)

Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, Page DC. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2474-9. doi: 10.1073/pnas.0510813103. Epub 2006 Feb 6.

Reference Type BACKGROUND
PMID: 16461896 (View on PubMed)

Anderson EL, Baltus AE, Roepers-Gajadien HL, Hassold TJ, de Rooij DG, van Pelt AM, Page DC. Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14976-80. doi: 10.1073/pnas.0807297105. Epub 2008 Sep 17.

Reference Type BACKGROUND
PMID: 18799751 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19465599 (View on PubMed)

Dufour JM, Kim KH. Cellular and subcellular localization of six retinoid receptors in rat testis during postnatal development: identification of potential heterodimeric receptors. Biol Reprod. 1999 Nov;61(5):1300-8. doi: 10.1095/biolreprod61.5.1300.

Reference Type BACKGROUND
PMID: 10529278 (View on PubMed)

Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P. Function of retinoic acid receptor gamma in the mouse. Cell. 1993 May 21;73(4):643-58. doi: 10.1016/0092-8674(93)90246-m.

Reference Type BACKGROUND
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)

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.

Reference Type BACKGROUND
PMID: 16586441 (View on PubMed)

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
PMID: 1398387 (View on PubMed)

Vogt HJ, Ewers R. [13-cis-Retinoic acid and spermatogenesis. Spermatological and impulse cytophotometric studies]. Hautarzt. 1985 May;36(5):281-6. German.

Reference Type BACKGROUND
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.

Reference Type BACKGROUND
PMID: 3481225 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23413144 (View on PubMed)

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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K24HD082231

Identifier Type: NIH

Identifier Source: secondary_id

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STUDY00001055

Identifier Type: -

Identifier Source: org_study_id