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| ID | Type | Description | Link |
|---|---|---|---|
| U54HD012629 | 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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The purpose of this investigational study is to determine how much male hormone, testosterone, is necessary to maintain sperm production in the testis. This knowledge will be used to help in the development of a safe male hormonal contraception.
Three study drugs will be used in this study: Testim (testosterone gel), Human Chorionic Gonadotropin (hCG) and acyline. Testosterone is a naturally occurring hormone in men. When given to normal men, testosterone gel will temporarily lower the amount of testosterone in the testes and lower sperm counts. hCG is a female hormone produced during pregnancy that is similar to and has the same actions as a male hormone, luteinizing hormone (LH). Like LH, hCG stimulates the testis to produce testosterone and sperm, and is used in the treatment of men who are deficient in LH. When hCG is given together with testosterone to normal men, the amount of testosterone in the testes will change, dependent on the amount of hCG received. Some participants will receive placebo hCG injections (no active medication).
Acyline suppresses LH (luteinizing hormone) and FSH (follicle stimulating hormone), which are hormones made by the pituitary gland in the brain, thus blocking the signal from the brain that causes the testes to make testosterone. Therefore, acyline blocks testosterone production. Men may experience some side effects from the low levels of testosterone caused by acyline.
Acyline is an experimental drug. Testosterone gel and hCG are approved for use in men with low testosterone levels. The U.S. Food and Drug Administration (FDA) allows testosterone gel, hCG and acyline to be given in combination for research to a small number of volunteers. Over 125 men have received acyline. Both Acyline and hCG will be given by injection. Acyline injections are formulated by subjects weight and may be given in multiple injections.
Participation will last approximately 2 months. The study involves a minimum of 9 visits in Seattle, WA. Clinic visits at Screening, Day 1 and Day 10 will take about 1-1.5 hours each. On Day 1 & 10 a fine needle aspiration of one testis will be performed. The Day 7, Day 17, and Day 40 visits will take approximately 30 minutes. The other visits will take about 15 minutes each time. Over the course of the study, which includes 5 separate blood draws, approximately 12 ounces (one and a half cups) of blood will be drawn. Some of the study drugs will be given by injection. One drug is a topical gel.
This is NOT a trial of a male contraceptive, and the study medications will not prevent pregnancy. Subjects must use an acceptable form of birth control.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acyline plus Placebo | Experimental | Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days |
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| Acyline plus 15 IU hCG | Experimental | Acyline 300 ug/kg (SQ) inj(s) on Day 1 plus subcutaneous 15 IU hCG injection (inj) every other day (5 doses) for 10 days |
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| Acyline plus 60 IU hCG | Experimental | Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous 60 IU hCG injection (inj) every other day (5 doses) for 10 days |
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| Acyline plus 125 IU hCG | Experimental | Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous 125 IU hCG injection (inj) every other day (5 doses) for 10 days |
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| Acyline plus Testosterone gel | Experimental | Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acyline | Drug | 300 ug/kg subcutaneous injections on Day 1. |
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| Measure | Description | Time Frame |
|---|---|---|
| Serum Testosterone (T) | 10 days | |
| Serum Luteinizing Hormone (LH) | 10 days | |
| Serum Follicle Stimulating Hormone (FSH) | 10 days | |
| Intratesticular Testosterone (ITT-T) | 10 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William Bremner, MD, PhD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Washington | Seattle | Washington | 98195 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 1977002 | Background | Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet. 1990 Oct 20;336(8721):955-9. | |
| 8774299 | Background | Wu FC, Farley TM, Peregoudov A, Waites GM. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Fertil Steril. 1996 Mar;65(3):626-36. |
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2 of 61 men decided not to enroll. 19 failed inclusion criteria, 1 withdrew consent before study procedures, 1 dropped out after Day 1, and 1 was withdrawn by the investigator for syncopal reaction. 6 did not suppress serum luteinizing hormone(affecting intratesticular testosterone)and were excluded from analysis. 31 completed the study.
Subjects were recruited using rosters from prior research studies and newspaper and online advertisements.
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| ID | Title | Description |
|---|---|---|
| FG000 | Acyline Plus Placebo | Acyline (ACY) 300 ug/kg subcutaneous (SQ) injections on Day 1 plus SQ placebo hCG every other day(q.o.d) (5 doses) for 10 days |
| FG001 | Acyline Plus 15 IU hCG |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| placebo hCG (no active ingredient) | Other | placebo hCG |
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| hCG (human chorionic gonadotropin) | Drug | 15 IU subcutaneous injection every other day for 10 days (5 doses) |
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| hCG (human chorionic gonadotropin) | Drug | 60 IU subcutaneous injection |
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| hCG (human chorionic gonadotropin) | Drug | 125 IU subcutaneous injection |
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| Testosterone gel | Drug | 75 mg testosterone gel applied transdermally for 10 days |
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| 10386821 | Background | Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl. 1999 May-Jun;20(3):407-14. |
| 2498065 | Background | Zirkin BR, Santulli R, Awoniyi CA, Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology. 1989 Jun;124(6):3043-9. doi: 10.1210/endo-124-6-3043. |
| 15713727 | Background | Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, Sutton PR, Wright WW, Brown TR, Yan X, Zirkin BR, Jarow JP. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab. 2005 May;90(5):2595-602. doi: 10.1210/jc.2004-0802. Epub 2005 Feb 15. |
| 15477366 | Background | Coviello AD, Bremner WJ, Matsumoto AM, Herbst KL, Amory JK, Anawalt BD, Yan X, Brown TR, Wright WW, Zirkin BR, Jarow JP. Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen. J Androl. 2004 Nov-Dec;25(6):931-8. doi: 10.1002/j.1939-4640.2004.tb03164.x. |
| 2113863 | Background | Awoniyi CA, Sprando RL, Santulli R, Chandrashekar V, Ewing LL, Zirkin BR. Restoration of spermatogenesis by exogenously administered testosterone in rats made azoospermic by hypophysectomy or withdrawal of luteinizing hormone alone. Endocrinology. 1990 Jul;127(1):177-84. doi: 10.1210/endo-127-1-177. |
| 8056636 | Background | Chen H, Chandrashekar V, Zirkin BR. Can spermatogenesis be maintained quantitatively in intact adult rats with exogenously administered dihydrotestosterone? J Androl. 1994 Mar-Apr;15(2):132-8. |
| 12185103 | Background | Meriggiola MC, Costantino A, Bremner WJ, Morselli-Labate AM. Higher testosterone dose impairs sperm suppression induced by a combined androgen-progestin regimen. J Androl. 2002 Sep-Oct;23(5):684-90. |
| 20484472 | Result | Roth MY, Page ST, Lin K, Anawalt BD, Matsumoto AM, Snyder CN, Marck BT, Bremner WJ, Amory JK. Dose-dependent increase in intratesticular testosterone by very low-dose human chorionic gonadotropin in normal men with experimental gonadotropin deficiency. J Clin Endocrinol Metab. 2010 Aug;95(8):3806-13. doi: 10.1210/jc.2010-0360. Epub 2010 May 19. |
| 23040523 | Result | Roth MY, Lin K, Bay K, Amory JK, Anawalt BD, Matsumoto AM, Marck BT, Bremner WJ, Page ST. Serum insulin-like factor 3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low-dose human chorionic gonadotropin: a randomized, controlled trial. Fertil Steril. 2013 Jan;99(1):132-139. doi: 10.1016/j.fertnstert.2012.09.009. Epub 2012 Oct 3. |
ACY 300 ug/kg SQ on Day 1 plus SQ 15 IU hCG q.o.d (5 doses) for 10 days
| FG002 | Acyline Plus 60 IU hCG | ACY 300 ug/kg SQ Day 1 + 60 IU hCG SQ q.o.d (5 doses) for 10 days |
| FG003 | Acyline Plus 125 IU hCG | ACY 300 ug/kg SQ Day 1 + 125 IU hCG SQ q.o.d (5 doses) for 10 days |
| FG004 | Acyline Plus Testosterone Gel | ACY 300 ug/kg SQ on Day 1 + Testosterone gel 75 mg/day daily for 10 days |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Acyline Plus Placebo | Acyline (ACY) 300 ug/kg subcutaneous (SQ) injections on Day 1 plus SQ placebo hCG every other day(q.o.d) (5 doses) for 10 days |
| BG001 | Acyline Plus 15 IU hCG | ACY 300 ug/kg SQ on Day 1 plus SQ 15 IU hCG q.o.d (5 doses) for 10 days |
| BG002 | Acyline Plus 60 IU hCG | ACY 300 ug/kg SQ Day 1 + 60 IU hCG SQ q.o.d (5 doses) for 10 days |
| BG003 | Acyline Plus 125 IU hCG | ACY 300 ug/kg SQ Day 1 + 125 IU hCG SQ q.o.d (5 doses) for 10 days |
| BG004 | Acyline Plus Testosterone Gel | ACY 300 ug/kg SQ on Day 1 + Testosterone gel 75 mg/day daily for 10 days |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Body Mass Index (BMI) | Median | Inter-Quartile Range | kg/m^2 |
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| Serum Luteinizing Hormone (LH) | Median | Inter-Quartile Range | IU/L |
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| Serum Follicle Simulating Hormone (FSH) | Median | Inter-Quartile Range | IU/L |
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| Serum Testosterone (T) | Median | Inter-Quartile Range | nmol/L |
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| Serum Dihydrotestosterone (DHT) | Median | Inter-Quartile Range | nmol/L |
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| Serum Estradiol | Median | Inter-Quartile Range | pmol/L |
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| Serum 17-Hydroxyprogesterone | Median | Inter-Quartile Range | nmol/L |
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| Intratesticular Testosterone (ITT-T) | Median | Inter-Quartile Range | nmol/L |
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| Intratesticular Dihydrotestosterone (ITT-DHT) | Median | Inter-Quartile Range | nmol/L |
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| 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 | Serum Testosterone (T) | Analysis per protocol. Due to nonnormality, the data were expressed as medians and 25th and 75 percentiles. Analysis of both baseline and end of treatment hormone concentrations performed on 31 subjects who completed all study procedures and who suppressed serum LH below the lower limit of normal at end of treatment. | Posted | Median | Inter-Quartile Range | nmol/liter | 10 days |
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| Primary | Serum Luteinizing Hormone (LH) | Posted | Median | Inter-Quartile Range | IU/L | 10 days |
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| Primary | Serum Follicle Stimulating Hormone (FSH) | Posted | Median | Inter-Quartile Range | IU/L | 10 days |
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| Primary | Intratesticular Testosterone (ITT-T) | Posted | Oct 2010 | Median | Inter-Quartile Range | IU/L | 10 days |
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overall study (1 year, 5 months)
The first subject was screened 3/17/09; the last subject exited 8/17/10. Subjects in the study are asked about adverse events and concomitant medications at every visit.
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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 | Acyline Plus Placebo | Acyline (ACY) 300 ug/kg subcutaneous (SQ) injections on Day 1 plus SQ placebo hCG every other day(q.o.d) (5 doses) for 10 days | 0 | 6 | 1 | 6 | ||
| EG001 | Acyline Plus 15 IU hCG | ACY 300 ug/kg SQ on Day 1 plus SQ 15 IU hCG q.o.d (5 doses) for 10 days | 0 | 7 | 1 | 7 | ||
| EG002 | Acyline Plus 60 IU hCG | ACY 300 ug/kg SQ Day 1 + 60 IU hCG SQ q.o.d (5 doses) for 10 days | 0 | 5 | 3 | 5 | ||
| EG003 | Acyline Plus 125 IU hCG | ACY 300 ug/kg SQ Day 1 + 125 IU hCG SQ q.o.d (5 doses) for 10 days | 0 | 5 | 2 | 5 | ||
| EG004 | Acyline Plus Testosterone Gel | ACY 300 ug/kg SQ on Day 1 + Testosterone gel 75 mg/day daily for 10 days | 0 | 8 | 1 | 8 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hot flashes | Endocrine disorders | Systematic Assessment |
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| dry itchy skin | Skin and subcutaneous tissue disorders | Systematic Assessment | dry itchy skin at site of gel application |
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| fatigue | General disorders | Systematic Assessment | fatigue for 12 days |
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| decreased libido | Endocrine disorders | Systematic Assessment |
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| testicular soreness | Reproductive system and breast disorders | Systematic Assessment |
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| syncope | Nervous system disorders | Systematic Assessment |
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| slight dizziness | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mara Roth, MD | University of Washington | 206-221-0519 | mylang@u.washington.edu |
| ID | Term |
|---|---|
| C109238 | acyline |
| D006063 | Chorionic Gonadotropin |
| D013739 | Testosterone |
| ID | Term |
|---|---|
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
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| Male |
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