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

NCT03323801 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: STUDY00001055K24HD082231
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Male Infertility, Azoospermia

Keywords

Infertility

Outcome Measures

Primary Outcomes (2)

• Total Motile Sperm

  Number of participants with undetectable or detectable sperm in their ejaculates.

  up to 32 weeks

• Total Sperm and Percentage of These Sperm That Were Motile

  Number of total sperm in ejaculate and percentage of these sperm that were motile

  32 weeks

Secondary Outcomes (1)

• Serious and Non-Serious Adverse Effects

  32 weeks

Study Arms (1)

13-cis retinoic acid

EXPERIMENTAL

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

Drug: 13-cis retinoic acid

Interventions

13-cis retinoic acid DRUG

Accutane is used for the treatment of severe acne

Also known as: Accutane, Isotretinoin

13-cis retinoic acid

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

Sponsors & Collaborators

• University of Washington: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (16)

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  PMID: 8102079 BACKGROUND

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

  PMID: 9074589 BACKGROUND

• 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.

  PMID: 19247918 BACKGROUND

• 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.

  PMID: 10506831 BACKGROUND

• 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.

  PMID: 17905941 BACKGROUND

• 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.

  PMID: 16461896 BACKGROUND

• 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.

  PMID: 18799751 BACKGROUND

• 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.

  PMID: 19465599 BACKGROUND

• 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.

  PMID: 10529278 BACKGROUND

• 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.

  PMID: 8388780 BACKGROUND

• 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.

  PMID: 8394014 BACKGROUND

• 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.

  PMID: 16586441 BACKGROUND

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

  PMID: 1398387 BACKGROUND

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

  PMID: 3159708 BACKGROUND

• 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.

  PMID: 3481225 BACKGROUND

• 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.

  PMID: 23413144 BACKGROUND

MeSH Terms

Conditions

Infertility, Male; Azoospermia; Infertility

Interventions

Isotretinoin

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Dr. John Amory
• Organization: University of Washington School of Medicine

jamory@uw.edu

2066161727

Study Officials

• John K Amory, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, School of Medicine, General Internal Medicine

Model Details: 20 mg 13-cis retinoic acid twice daily (BID) with meals for 32 weeks

Study Record Dates

• First Submitted: October 24, 2017
• First Posted: October 27, 2017
• Study Start: July 25, 2017
• Primary Completion: May 16, 2019
• Study Completion: May 31, 2019
• Last Updated: October 26, 2021
• Results First Posted: October 26, 2021

Record last verified: 2021-09

Locations

US (1)