CompletedNCT00839319HOP-3Updated Jan 11, 2016Results posted

HOP-3 Manipulation of the Intratesticular Hormonal Milieu With Exogenous Testosterone

A Phase 1/2 interventional study of Acyline and placebo hCG (no active ingredient) in Healthy Males, sponsored by University of Washington. Completed at 1 site in United States. Open to male participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-01-11.

Sponsored by University of Washington · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 59
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: Male

Study summary

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.

Read the detailed description

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.

Conditions studied

Healthy Males

Keywords

hCG
testosterone
Acyline
Intratesticular hormone

In context

Lead sponsor

University of Washington is the lead sponsor of 1,397 studies on the registry; 225 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 132 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: Male
Accepts healthy volunteers: Yes

Inclusion criteria

Males age 18-50
Normal serum testosterone, LH and FSH
PSA \< 4.0
Agrees not to donate blood or participate in another research study during the study
Informed consent
In general good health based on normal screening evaluation (consisting of a medical history, physical exam, normal sperm count, normal serum chemistry and hematology)
Must be willing to use a reliable form of contraception during the study

Exclusion criteria

Exclusion Criteria:

Oligospermia (sperm count \< 15 million/mL after 48 hours of abstinence) and/or abnormal motility or morphology.
Participation in a long-term male contraceptive study within the past three months
History of testosterone or anabolic steroid abuse in the past
Poor general health with significantly abnormal blood results
History of or current testicular disease
History of a bleeding disorder or need for anticoagulation
History of sleep apnea and/or major psychiatric problems
BMI > 32
Subjects with a skin condition that might interfere or be exacerbated by testosterone gel use
Subject's with alcohol or drug use

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 59 participants (actual)

Study arms

Experimental
Acyline plus Placebo
Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days
Drug: Acyline · Other: placebo hCG (no active ingredient)
Experimental
Acyline plus 15 IU hCG
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
Drug: Acyline · Drug: hCG (human chorionic gonadotropin)
Experimental
Acyline plus 60 IU hCG
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
Drug: Acyline · Drug: hCG (human chorionic gonadotropin)
Experimental
Acyline plus 125 IU hCG
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
Drug: Acyline · Drug: hCG (human chorionic gonadotropin)
Experimental
Acyline plus Testosterone gel
Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days
Drug: Acyline · Drug: Testosterone gel

Interventions

DrugAcyline
300 ug/kg subcutaneous injections on Day 1.
Also known as: Acyline GhRH antagonist
Otherplacebo hCG (no active ingredient)
placebo hCG
Also known as: placebo drug
DrughCG (human chorionic gonadotropin)
15 IU subcutaneous injection every other day for 10 days (5 doses)
Also known as: Pregnyl
DrughCG (human chorionic gonadotropin)
60 IU subcutaneous injection
Also known as: Pregnyl
DrughCG (human chorionic gonadotropin)
125 IU subcutaneous injection
Also known as: Pregnyl
DrugTestosterone gel
75 mg testosterone gel applied transdermally for 10 days
Also known as: Testim

What researchers measure

Primary outcomes

Serum Testosterone (T)
Time frame: 10 days
Serum Luteinizing Hormone (LH)
Time frame: 10 days
Serum Follicle Stimulating Hormone (FSH)
Time frame: 10 days
Intratesticular Testosterone (ITT-T)
Time frame: 10 days

Results

Posted Nov 16, 2010

Participant flow

Subjects were recruited using rosters from prior research studies and newspaper and online advertisements.

Participant flow — Overall Study
Milestone	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel
Started	8	8	8	8	8
Completed	6	7	5	5	8
Not completed	2	1	3	3	0

Outcome measures

PrimarySerum Testosterone (T)

Time frame:: 10 days
Reported as:: Median · nmol/liter

Serum Testosterone (T)
nmol/liter	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel
Serum Testosterone (T)	0.43 (0.35 to 0.76)	1.5 (0.79 to 4.9)	3.7 (1 to 8.5)	8.4 (4.9 to 11)	16 (13 to 20)

Statistical analysis

Acyline Plus Placebo vs Acyline Plus 15 IU hCG vs Acyline Plus 60 IU hCG vs Acyline Plus 125 IU hCG · ANOVA · p = <0.05Correlations between serum hormone levels and IT hormones, and between IT hormones were performed on 23 subjects in 4 groups using Spearmen technique.

PrimarySerum Luteinizing Hormone (LH)

Time frame:: 10 days
Reported as:: Median · IU/L

Serum Luteinizing Hormone (LH)
IU/L	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel
Serum Luteinizing Hormone (LH)	0.13 (0.07 to 0.23)	0.28 (0.2 to 1.63)	0.49 (0.16 to 1.3)	0.39 (0.28 to 1.7)	0.14 (0.05 to 0.62)

PrimarySerum Follicle Stimulating Hormone (FSH)

Time frame:: 10 days
Reported as:: Median · IU/L

Serum Follicle Stimulating Hormone (FSH)
IU/L	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel
Serum Follicle Stimulating Hormone (FSH)	0.41 (0.17 to 0.46)	0.41 (0.27 to 0.6)	0.29 (0.24 to 1.0)	0.28 (0.25 to 1.1)	0.21 (0.18 to 0.27)

PrimaryIntratesticular Testosterone (ITT-T)

Time frame:: 10 days
Reported as:: Median · IU/L

Intratesticular Testosterone (ITT-T)
IU/L	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel
Intratesticular Testosterone (ITT-T)	77 (40 to 223)	136 (79 to 258)	319 (139 to 2455)	987 (895 to 1250)	73 (34 to 264)

Adverse events

Collected over overall study (1 year, 5 months). Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Acyline Plus Placebo	—	0/6 (0%)	1/6 (16.7%)
Acyline Plus 15 IU hCG	—	0/7 (0%)	1/7 (14.3%)
Acyline Plus 60 IU hCG	—	0/5 (0%)	3/5 (60%)
Acyline Plus 125 IU hCG	—	0/5 (0%)	2/5 (40%)
Acyline Plus Testosterone Gel	—	0/8 (0%)	1/8 (12.5%)

Most frequent other events

Most frequent other events
Event	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel
fatigueGeneral disorders	0/6	0/7	1/5	0/5	0/8
decreased libidoEndocrine disorders	0/6	0/7	1/5	0/5	0/8
testicular sorenessReproductive system and breast disorders	0/6	0/7	0/5	1/5	0/8
syncopeNervous system disorders	0/6	0/7	1/5	0/5	0/8
slight dizzinessNervous system disorders	0/6	0/7	0/5	1/5	0/8
hot flashesEndocrine disorders	1/6	1/7	0/5	0/5	0/8
dry itchy skinSkin and subcutaneous tissue disorders	0/6	0/7	0/5	0/5	1/8

Baseline characteristics

Age, Customized
Age, Customized(years)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Median	21 (20 to 26)	25 (20 to 29)	22 (20 to 24)	22 (21 to 26)	22 (20 to 24)	22 (20 to 26)

Sex: Female, Male
Sex: Female, Male(Participants)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Female	0	0	0	0	0	0
Male	6	7	5	5	8	31

Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Median	24.8 (23.6 to 26.3)	24.1 (23.2 to 26.7)	24.9 (21.2 to 26.3)	25.8 (22.9 to 26)	23.7 (21.1 to 25.4)	24.1 (22.9 to 26.3)

Serum Luteinizing Hormone (LH)
Serum Luteinizing Hormone (LH)(IU/L)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Median	3.5 (3.1 to 4.8)	3.0 (2.6 to 4.9)	3.4 (3.4 to 4.9)	2.9 (2.3 to 3.7)	3.8 (2.6 to 4.6)	3.4 (2.6 to 4.9)

Serum Follicle Simulating Hormone (FSH)
Serum Follicle Simulating Hormone (FSH)(IU/L)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Median	2.7 (1.2 to 3.4)	2.4 (2 to 2.8)	2.6 (2.2 to 3.2)	2.2 (1.9 to 2.5)	1.9 (1.3 to 2.8)	2.4 (1.5 to 3.0)

Serum Testosterone (T)
Serum Testosterone (T)(nmol/L)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Median	13.0 (11.3 to 16.9)	15.0 (11.4 to 20.9)	14.2 (12.7 to 14.9)	16.8 (14.4 to 18.6)	15.0 (13.7 to 18.3)	14.6 (12 to 17.3)

Serum Dihydrotestosterone (DHT)
Serum Dihydrotestosterone (DHT)(nmol/L)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Median	1.0 (0.7 to 1.5)	1.3 (0.9 to 1.7)	1.2 (1 to 1.3)	0.9 (0.7 to 1.5)	1.1 (1.1 to 1.2)	1.1 (0.9 to 1.4)

Serum Estradiol
Serum Estradiol(pmol/L)	Acyline Plus Placebo	Acyline Plus 15 IU hCG	Acyline Plus 60 IU hCG	Acyline Plus 125 IU hCG	Acyline Plus Testosterone Gel	Total
Median	89 (47 to 150)	65 (34 to 125)	62 (48 to 78)	77 (44 to 95)	86 (54 to 95)	77 (46 to 104)

3 further baseline measures are reported on the registry.

Study locations

1 site

University of Washington
Seattle, Washington 98195, United States

References and documents

Publications

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. PubMed 1977002 ↗
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. PubMed 8774299 ↗
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. PubMed 10386821 ↗
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. PubMed 2498065 ↗
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. PubMed 15713727 ↗
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. PubMed 15477366 ↗
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. PubMed 2113863 ↗
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. PubMed 8056636 ↗
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. PubMed 12185103 ↗
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. PubMed 20484472 ↗
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. PubMed 23040523 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 11, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00839319
Lead sponsor: University of Washington
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party: John Amory (Professor, Department of Medicine, University of Washington) — Principal investigator
First posted: Feb 9, 2009
Start date: Mar 2009
Primary completion: Sep 2010
Completion: Nov 2010
Results posted: Nov 16, 2010
Last update: Jan 11, 2016

Study contacts

William Bremner, MD, PhD

principal investigator · University of Washington

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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