Healthy Males
Conditions
Keywords
hCG, testosterone, Acyline, Intratesticular hormone
Brief 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.
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.
Interventions
DRUGAcyline
300 ug/kg subcutaneous injections on Day 1.
OTHERplacebo hCG (no active ingredient)
placebo hCG
15 IU subcutaneous injection every other day for 10 days (5 doses)
DRUGTestosterone gel
75 mg testosterone gel applied transdermally for 10 days
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
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
* 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
Design outcomes
Primary
| Measure | 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 |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited using rosters from prior research studies and newspaper and online advertisements.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 6 |
| 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 | 7 |
| Acyline Plus 60 IU hCG ACY 300 ug/kg SQ Day 1 + 60 IU hCG SQ q.o.d (5 doses) for 10 days | 5 |
| Acyline Plus 125 IU hCG ACY 300 ug/kg SQ Day 1 + 125 IU hCG SQ q.o.d (5 doses) for 10 days | 5 |
| Acyline Plus Testosterone Gel ACY 300 ug/kg SQ on Day 1 + Testosterone gel 75 mg/day daily for 10 days | 8 |
| Total | 31 |
Baseline characteristics
| Characteristic | Acyline Plus Placebo | Acyline Plus 15 IU hCG | Acyline Plus 60 IU hCG | Acyline Plus 125 IU hCG | Acyline Plus Testosterone Gel | Total |
|---|---|---|---|---|---|---|
| Age, Customized | 21 years | 25 years | 22 years | 22 years | 22 years | 22 years |
| Body Mass Index (BMI) | 24.8 kg/m^2 | 24.1 kg/m^2 | 24.9 kg/m^2 | 25.8 kg/m^2 | 23.7 kg/m^2 | 24.1 kg/m^2 |
| Intratesticular Dihydrotestosterone (ITT-DHT) | 18.0 nmol/L | 5.0 nmol/L | 7.6 nmol/L | 18.8 nmol/L | 12.9 nmol/L | 11.9 nmol/L |
| Intratesticular Testosterone (ITT-T) | 3467 nmol/L | 2425 nmol/L | 1821 nmol/L | 3502 nmol/L | 2933 nmol/L | 2508 nmol/L |
| Serum 17-Hydroxyprogesterone | 4.7 nmol/L | 4.9 nmol/L | 5.9 nmol/L | 4.3 nmol/L | 4.6 nmol/L | 4.9 nmol/L |
| Serum Dihydrotestosterone (DHT) | 1.0 nmol/L | 1.3 nmol/L | 1.2 nmol/L | 0.9 nmol/L | 1.1 nmol/L | 1.1 nmol/L |
| Serum Estradiol | 89 pmol/L | 65 pmol/L | 62 pmol/L | 77 pmol/L | 86 pmol/L | 77 pmol/L |
| Serum Follicle Simulating Hormone (FSH) | 2.7 IU/L | 2.4 IU/L | 2.6 IU/L | 2.2 IU/L | 1.9 IU/L | 2.4 IU/L |
| Serum Luteinizing Hormone (LH) | 3.5 IU/L | 3.0 IU/L | 3.4 IU/L | 2.9 IU/L | 3.8 IU/L | 3.4 IU/L |
| Serum Testosterone (T) | 13.0 nmol/L | 15.0 nmol/L | 14.2 nmol/L | 16.8 nmol/L | 15.0 nmol/L | 14.6 nmol/L |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 5 Participants | 5 Participants | 8 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 7 | 3 / 5 | 2 / 5 | 1 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 0 / 5 | 0 / 5 | 0 / 8 |
Outcome results
Primary
Intratesticular Testosterone (ITT-T)
Time frame: 10 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acyline Plus Placebo | Intratesticular Testosterone (ITT-T) | 77 IU/L |
| Acyline Plus 15 IU hCG | Intratesticular Testosterone (ITT-T) | 136 IU/L |
| Acyline Plus 60 IU hCG | Intratesticular Testosterone (ITT-T) | 319 IU/L |
| Acyline Plus 125 IU hCG | Intratesticular Testosterone (ITT-T) | 987 IU/L |
| Acyline Plus Testosterone Gel | Intratesticular Testosterone (ITT-T) | 73 IU/L |
Primary
Serum Follicle Stimulating Hormone (FSH)
Time frame: 10 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acyline Plus Placebo | Serum Follicle Stimulating Hormone (FSH) | 0.41 IU/L |
| Acyline Plus 15 IU hCG | Serum Follicle Stimulating Hormone (FSH) | 0.41 IU/L |
| Acyline Plus 60 IU hCG | Serum Follicle Stimulating Hormone (FSH) | 0.29 IU/L |
| Acyline Plus 125 IU hCG | Serum Follicle Stimulating Hormone (FSH) | 0.28 IU/L |
| Acyline Plus Testosterone Gel | Serum Follicle Stimulating Hormone (FSH) | 0.21 IU/L |
Primary
Serum Luteinizing Hormone (LH)
Time frame: 10 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acyline Plus Placebo | Serum Luteinizing Hormone (LH) | 0.13 IU/L |
| Acyline Plus 15 IU hCG | Serum Luteinizing Hormone (LH) | 0.28 IU/L |
| Acyline Plus 60 IU hCG | Serum Luteinizing Hormone (LH) | 0.49 IU/L |
| Acyline Plus 125 IU hCG | Serum Luteinizing Hormone (LH) | 0.39 IU/L |
| Acyline Plus Testosterone Gel | Serum Luteinizing Hormone (LH) | 0.14 IU/L |
Primary
Serum Testosterone (T)
Time frame: 10 days
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acyline Plus Placebo | Serum Testosterone (T) | 0.43 nmol/liter |
| Acyline Plus 15 IU hCG | Serum Testosterone (T) | 1.5 nmol/liter |
| Acyline Plus 60 IU hCG | Serum Testosterone (T) | 3.7 nmol/liter |
| Acyline Plus 125 IU hCG | Serum Testosterone (T) | 8.4 nmol/liter |
| Acyline Plus Testosterone Gel | Serum Testosterone (T) | 16 nmol/liter |
p-value: <0.05ANOVA