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| ID | Type | Description | Link |
|---|---|---|---|
| K24HD082231 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 13-cis retinoic acid | Experimental | 20 mg 13-cis retinoic acid twice daily (BID) with means for 32 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 13-cis retinoic acid | Drug | Accutane is used for the treatment of severe acne |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Serious and Non-Serious Adverse Effects | Number of participants with Serious and Non-Serious Adverse effects associated with treatment with 13-cis retinoic acid | 32 weeks |
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Inclusion Criteria: Infertile men with azoospermia on at least two semen analyses separated by at least one week, and no pregnancy with partner with normal cycles and normal hysterosalpingogram despite >1 year of unprotected intercourse.
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Exclusion Criteria: hypogonadotropic hypogonadism (that might respond to gonadotropin injections); use of anabolic steroids,illicit drugs, or consumption of more than 4 alcoholic beverages daily; current therapy with retinoic acid (eg Accutane) or vitamin A- of use of isotretinoin within eight weeks of start of dosing;phenytoin, or medication containing tetracycline; personal history of serious psychiatric disorders, score of greater than 15 on the PHQ9 (mood) questionnaire; elevated serum serum triglycerides or other abnormal serum chemistry values; history of inflammatory bowel disease or bone disease; not living within catchment area; participation in another clinical trial
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| Name | Affiliation | Role |
|---|---|---|
| John K Amory, MD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Washington Medical Center | Seattle | Washington | 98195 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8102079 | Background | 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. | |
| 9074589 | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 13-cis Retinoic Acid | 20 mg 13-cis retinoic acid twice daily (BID) with means for 32 weeks 13-cis retinoic acid: Accutane is used for the treatment of severe acne |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Men with infertility due to azoospermia
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| ID | Title | Description |
|---|---|---|
| BG000 | 13-cis Retinoic Acid | 20 mg 13-cis retinoic acid twice daily (BID) with means for 32 weeks 13-cis retinoic acid: Accutane is used for the treatment of severe acne |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Motile Sperm | Number of participants with undetectable or detectable sperm in their ejaculates. | Men had idiopathic azoospermia, without evidence of obstruction or know genetic causes of azoospermia, although one man had known AZFc deletion | Posted | Count of Participants | Participants | up to 32 weeks |
|
|
32 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Accutane-13-cis Retinoic Acid | 20 mg 13-cis retinoic acid twice daily (BID) with means for 32 weeks 13-cis retinoic acid: Accutane is used for the treatment of severe acne |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nephrotic syndrome | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| cramps | Musculoskeletal and connective tissue disorders | Systematic Assessment | Muscle cramps |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. John Amory | University of Washington School of Medicine | 2066161727 | jamory@uw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 12, 2017 | May 30, 2021 | Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 23, 2017 | Apr 26, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D007248 | Infertility, Male |
| D053713 | Azoospermia |
| D007246 | Infertility |
| ID | Term |
|---|---|
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D015474 | Isotretinoin |
| ID | Term |
|---|---|
| D012176 | Retinoids |
| D002338 | Carotenoids |
| D011090 | Polyenes |
| D000475 | Alkenes |
| D006839 |
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20 mg 13-cis retinoic acid twice daily (BID) with meals for 32 weeks
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| 19247918 | 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. |
| 10506831 | 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. |
| 17905941 | 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. |
| 16461896 | 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. |
| 18799751 | 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. |
| 19465599 | 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. |
| 10529278 | 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. |
| 8388780 | 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. |
| 8394014 | 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. |
| 16586441 | 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. |
| 1398387 | 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. |
| 3159708 | Background | Vogt HJ, Ewers R. [13-cis-Retinoic acid and spermatogenesis. Spermatological and impulse cytophotometric studies]. Hautarzt. 1985 May;36(5):281-6. German. |
| 3481225 | 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. |
| 23413144 | 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. |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Total Sperm and Percentage of These Sperm That Were Motile | Number of total sperm in ejaculate and percentage of these sperm that were motile | Only man who developed sperm in ejaculate on treatment | Posted | Number | Percent of sperm that were motile | 32 weeks | Total sperm in the ejaculate | Total sperm in the ejaculate |
|
|
|
| Secondary | Serious and Non-Serious Adverse Effects | Number of participants with Serious and Non-Serious Adverse effects associated with treatment with 13-cis retinoic acid | Posted | Count of Participants | Participants | 32 weeks |
|
|
|
| 0 |
| 10 |
| 1 |
| 10 |
| 1 |
| 10 |
|
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| Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D013729 | Terpenes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |