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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01AG037603-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute on Aging (NIA) | NIH |
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The investigators will conduct a three-month, randomized, placebo-controlled trial comparing the effects of increasing doses of androgen supplementation with Testosterone (T) gel on the prostate in healthy men who are treated with acyline to block gonadal androgen production.
The investigators overall goals are (i) to determine the relationship between serum and prostate tissue hormone concentrations in men in response to increasing doses of exogenous androgens; (ii) to determine the impact that alterations in serum and tissue testosterone concentrations have on prostate epithelial cell function and phenotype; and (iii) to determine the relationships between prostatic androgens and alterations in the tissue microenvironment. The investigators will perform a study in healthy, middle-aged men to address the following Specific Aims:
Specific Aims: To compare the dose-response relationships between serum testosterone and intraprostatic androgens and androgen action, and serum testosterone and anabolic activity in healthy, middle-aged men.
Hypothesis: The investigators hypothesize that very low levels of serum testosterone will lower concentrations of intraprostatic testosterone and dihydrotestosterone (DHT). However, when serum testosterone concentrations are within or even above the normal range there will be no significant increases in intraprostatic testosterone and dihydrotestosterone. In contrast, the investigators expect that anabolic activity will increase with increasing concentrations of circulating testosterone.
Secondarily, the investigators hypothesize that increasing levels of serum testosterone beyond the low normal range will have little impact on androgen action within the prostate.
Approach: The investigators will conduct a randomized, placebo-controlled trial in healthy men who are medically castrated and administered one of five different doses of testosterone gel (Androgel) for 12 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Placebo | Placebo Comparator | Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks |
|
| Arm 2:1.25g Testosterone | Active Comparator | Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks |
|
| Arm 3: 2.5g Testosterone | Active Comparator | Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks |
|
| Arm 4: 5g Testosterone | Active Comparator | Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks |
|
| Arm 5: 10g Testosterone | Active Comparator | Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| placebo acyline | Other | Placebo acyline subcutaneous injection every 2 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Prostate Tissue DHT Concentrations After Treatment | To measure intraprostatic dihydrotestosterone [DHT] levels | 12 weeks |
| Serum Testosterone | 12 weeks | |
| Dihydrotestosterone (DHT) | 12 weeks | |
| Prostate Tissue Testosterone Concentrations After Treatment | To measure intraprostatic testosterone levels | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Prostate Specific Antigen | 12 weeks | |
| Prostate Volume | 12 weeks | |
| International Prostate Symptom Score (IPSS) |
| Measure | Description | Time Frame |
|---|---|---|
| 17-OHPreg | 12 weeks | |
| 17-OHP | 12 weeks | |
| Androstenedione |
Inclusion Criteria:
In good health, without severe systemic illness (i.e., renal, liver, cardiac or lung disease, cancer, insulin dependent diabetes)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephanie T Page, 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 |
|---|---|---|---|
| 27172434 | Result | Thirumalai A, Cooper LA, Rubinow KB, Amory JK, Lin DW, Wright JL, Marck BT, Matsumoto AM, Page ST. Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate Men Treated With Exogenous Testosterone. J Clin Endocrinol Metab. 2016 Jul;101(7):2937-44. doi: 10.1210/jc.2016-1483. Epub 2016 May 12. |
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98 screened. 28 screen fails (or did not finish screen). 8 subjects dropped out prior to drug start. 62 subjects started drug. 7 subjects dropped after drug start/pre-drug finish. 2 dropped after finishing study drug, but prior to prostate biopsy. 2 subjects dropped from analysis for non-compliance. 51 completed entire study, included in analysis.
Healthy males, 25-55 years old, were recruited via advertisement: flyers and newspaper ads at the University of Washington.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 (Placebo Acyline & Placebo T Gel ) | Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks placebo acyline: Placebo acyline subcutaneous injection every 2 weeks placebo gel: daily placebo testosterone gel applied transdermally x 12 weeks |
| FG001 | Arm 2 (Acyline & 1.25g Testosterone Gel) | Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks Testosterone 1% gel 1.25 g: testosterone 1% gel 1.25 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| FG002 | Arm 3 (Acyline & 2.5g Testosterone Gel) | Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks Testosterone 1% gel 2.5 g: Testosterone 1% gel 2.5 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| FG003 | Arm 4 (Acyline & 5g Testosterone Gel) | Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks Testosterone 1% gel 5.0 g: Testosterone 1% gel 5.0 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| FG004 | Arm 5 (Acyline & 10g Testosterone Gel) | Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks testosterone 1% gel 10 g: Testosterone 1% gel 10 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| FG005 | Arm 6 (Acyline & 15g Testosterone Gel) | Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks testosterone 1% gel 15 g: Testosterone 1% gel 15 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
62 subjects started treatment, 11 dropped after drug start & pre-study exit visit (7 dropped post-drug start but pre-drug finish, 2 dropped after drug finish but pre-prostate biopsy, 2 dropped for non-compliance). 51 participants included in the analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 | Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks placebo acyline: Placebo acyline subcutaneous injection every 2 weeks placebo gel: daily placebo testosterone gel applied transdermally x 12 weeks |
| BG001 | Arm 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Prostate Tissue DHT Concentrations After Treatment | To measure intraprostatic dihydrotestosterone [DHT] levels | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
Adverse events were recorded from day 1 through the end of study, Week 18. After the screening period, 12 weeks of treatment commenced for subjects who met inclusion/exclusion criteria, followed by a 6 week recovery period.
The 62 subjects who started study drugs on Day 0 were monitored for adverse events. Nine subjects were discontinued prior to study end. Two subjects were not included in data analysis due to medication non-compliance. Hence, while there were 51 subjects included in the analysis, 62 subjects (all who started study drugs) were monitored for adverse events.
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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 | Arm 1 | Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks placebo acyline: Placebo acyline subcutaneous injection every 2 weeks placebo gel: daily placebo testosterone gel applied transdermally x 12 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abnormal liver funtion tests | Hepatobiliary disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephanie Page, MD, PhD | University of Washington | 206-616-0483 | page@uw.edu |
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| ID | Term |
|---|---|
| D013739 | Testosterone |
| D005782 | Gels |
| C109238 | acyline |
| C092464 | LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)- |
| ID | Term |
|---|---|
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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| Arm 6: 15g Testosterone |
| Active Comparator |
Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks |
|
| placebo gel | Other | daily placebo testosterone gel applied transdermally x 12 weeks |
|
|
| Testosterone 1% gel 1.25 g | Drug | testosterone 1% gel 1.25 g daily applied transdermally x 12 weeks |
|
|
| Testosterone 1% gel 2.5 g | Drug | Testosterone 1% gel 2.5 g daily applied transdermally x 12 weeks |
|
|
| Testosterone 1% gel 5.0 g | Drug | Testosterone 1% gel 5.0 g daily applied transdermally x 12 weeks |
|
|
| testosterone 1% gel 10 g | Drug | Testosterone 1% gel 10 g daily applied transdermally x 12 weeks |
|
|
| testosterone 1% gel 15 g | Drug | Testosterone 1% gel 15 g daily applied transdermally x 12 weeks |
|
|
| Acyline | Drug | 300 ug/kg subcutaneous injection every 2 weeks |
|
|
IPSS score: 0-7 mildly symptomatic, 8-19 moderately symptomatic, 20-35 severely symptomatic |
| 12 weeks |
| 12 weeks |
| Androsterone | 12 weeks |
| DHEA | 12 weeks |
| Pregnenolone | 12 weeks |
| Progesterone | 12 weeks |
| Withdrawal by Subject |
|
| Physician Decision |
|
Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks Testosterone 1% gel 1.25 g: testosterone 1% gel 1.25 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| BG002 | Arm 3 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks Testosterone 1% gel 2.5 g: Testosterone 1% gel 2.5 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| BG003 | Arm 4 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks Testosterone 1% gel 5.0 g: Testosterone 1% gel 5.0 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| BG004 | Arm 5 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks testosterone 1% gel 10 g: Testosterone 1% gel 10 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| BG005 | Arm 6 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks testosterone 1% gel 15 g: Testosterone 1% gel 15 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Median | Inter-Quartile Range | kg^m2 |
|
| Testosterone Level | Median | Inter-Quartile Range | ng/dL |
|
| DHT Level | Median | Inter-Quartile Range | ng/dL |
|
| Lutenizing Hormone | Median | Inter-Quartile Range | mIU/mL |
|
| FSH | Median | Inter-Quartile Range | mIU/mL |
|
| Hematocrit | Median | Inter-Quartile Range | % |
|
| Prostate Specific Antigen (PSA) | Median | Inter-Quartile Range | ng/dL |
|
| Prostate volume | Median | Inter-Quartile Range | cm^3 |
|
| International Prostate Symptom Score (IPSS) | 0-7 mildly symptomatic, 8-19 moderately symptomatic, 20-35 severely symptomatic | Median | Inter-Quartile Range | units on a scale |
|
| Arm 3 Acyline Inject Every 2 Weeks & Daily T 1% Gel 2.5 |
Acyline (300ug/kg) subcutaneous injection every 2 weeks for 12 weeks & daily 1% testosterone (T) gel 2.5g applied transdermally for 12 weeks. |
| OG003 | Acyline Inject Every 2 Weeks & Daily T 1% Gel 5g | Acyline (300ug/kg) subcutaneous injection every 2 weeks for 12 weeks & daily 1% testosterone (T) gel 5g applied transdermally for 12 weeks. |
| OG004 | Acyline Inject Every 2 Weeks & Daily T 1% Gel 10g | Acyline (300ug/kg) subcutaneous injection every 2 weeks for 12 weeks & daily 1% testosterone (T) gel 10g applied transdermally for 12 weeks. |
| OG005 | Acyline Inject Every 2 Weeks & Daily T 1% Gel 15g | Acyline (300ug/kg) subcutaneous injection every 2 weeks for 12 weeks & daily 1% testosterone (T) gel 15g applied transdermally for 12 weeks. |
|
|
| Primary | Serum Testosterone | Posted | Median | Inter-Quartile Range | ng/mL | 12 weeks |
|
|
|
| Primary | Dihydrotestosterone (DHT) | Posted | Median | Inter-Quartile Range | ng/mL | 12 weeks |
|
|
|
| Primary | Prostate Tissue Testosterone Concentrations After Treatment | To measure intraprostatic testosterone levels | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| Secondary | Prostate Specific Antigen | Posted | Median | Inter-Quartile Range | ng/dL | 12 weeks |
|
|
|
| Secondary | Prostate Volume | Posted | Median | Inter-Quartile Range | cm^3 | 12 weeks |
|
|
|
| Secondary | International Prostate Symptom Score (IPSS) | IPSS score: 0-7 mildly symptomatic, 8-19 moderately symptomatic, 20-35 severely symptomatic | Posted | Median | Inter-Quartile Range | units on a scale | 12 weeks |
|
|
|
| Other Pre-specified | 17-OHPreg | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| Other Pre-specified | 17-OHP | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| Other Pre-specified | Androstenedione | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| Other Pre-specified | Androsterone | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| Other Pre-specified | DHEA | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| Other Pre-specified | Pregnenolone | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| Other Pre-specified | Progesterone | Posted | Median | Inter-Quartile Range | ng/g | 12 weeks |
|
|
|
| 0 |
| 10 |
| 7 |
| 10 |
| EG001 | Arm 2 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks Testosterone 1% gel 1.25 g: testosterone 1% gel 1.25 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks | 0 | 11 | 8 | 11 |
| EG002 | Arm 3 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks Testosterone 1% gel 2.5 g: Testosterone 1% gel 2.5 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks | 0 | 10 | 6 | 10 |
| EG003 | Arm 4 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks Testosterone 1% gel 5.0 g: Testosterone 1% gel 5.0 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks | 0 | 9 | 7 | 9 |
| EG004 | Arm 5 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks testosterone 1% gel 10 g: Testosterone 1% gel 10 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks | 0 | 11 | 10 | 11 |
| EG005 | Arm 6 | Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks testosterone 1% gel 15 g: Testosterone 1% gel 15 g daily applied transdermally x 12 weeks Acyline: 300 ug/kg subcutaneous injection every 2 weeks | 0 | 11 | 6 | 11 |
| Allergic reaction to Acyline | General disorders | Non-systematic Assessment |
|
| Discomfort at injection site | General disorders | Non-systematic Assessment |
|
| Hot flashes/night sweats | General disorders | Non-systematic Assessment |
|
| Insomnia | General disorders | Non-systematic Assessment |
|
| Mood changes (irritability) | General disorders | Non-systematic Assessment |
|
| Decreased libido | Endocrine disorders | Non-systematic Assessment |
|
| Increased libido | Endocrine disorders | Non-systematic Assessment |
|
| Decreased energy, fatigue | General disorders | Non-systematic Assessment |
|
| Erectile dysfunction | Endocrine disorders | Non-systematic Assessment |
|
| Semen changes (decreased ejaculation volume | Endocrine disorders | Non-systematic Assessment |
|
| Skin changes (acne, rash at site of T gel | General disorders | Non-systematic Assessment |
|
| Nipple discomfort | Endocrine disorders | Non-systematic Assessment |
|
| Testicular pain | Endocrine disorders | Non-systematic Assessment |
|
| Sexually transmitted disease | General disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Nausea, vomiting, abnormal bowl movements | General disorders | Non-systematic Assessment |
|
| Fever | General disorders | Non-systematic Assessment |
|
| Upper Respiratory infection/symptoms | Infections and infestations | Non-systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Injuries/accidents | General disorders | Non-systematic Assessment |
|
| Blood in semen | Endocrine disorders | Non-systematic Assessment |
|
| Bruise at injection site | General disorders | Non-systematic Assessment |
|
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| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |