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The purpose of this research study is to understand the effects of testosterone and estrogen on the body's response to the hormone insulin.
The investigators will examine the effects of testosterone on insulin sensitivity and body composition in men. This study may lend greater insight into the increased risk of diabetes evident in men with low circulating levels of testosterone. Three drugs will be used in this study: acyline, given by injection; testosterone (T) gel that is applied to the skin; and letrozole, which is an oral drug that blocks the conversion of androgens (male hormones) to estrogens (female hormones). Acyline inhibits the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH). When acyline stops the production of these hormones, it blocks the signal from the brain that stimulates the testicles to make testosterone. Adding testosterone to acyline will restore physiologic levels of testosterone in some study participants. One group of men will receive T gel with letrozole, an aromatase inhibitor; these men will have normal levels of testosterone but low levels of estrogen in the blood. This design will enable determination of the respective metabolic effects of testosterone and estrogen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acyline & placebo gel & placebo pill | Experimental | Acyline (300mcg/kg) + placebo transdermal gel + placebo pill daily |
|
| Acyline & Testosterone 1.25g & placebo pill | Experimental | Acyline (300mcg/kg) + Testosterone gel (1.25g) daily + placebo pill daily |
|
| Acyline & Testosterone 5g & placebo pill | Experimental | Acyline (300mcg/kg) + Testosterone gel (5g) daily + placebo pill daily |
|
| Acyline & Testosterone & Letrozole | Experimental | Acyline (300mcg/kg) + Testosterone gel (5g) daily + letrozole (5mg) daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acyline | Drug | 300 mcg/mL administered subcutaneously (at Day 0, Week 2) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity Quantified by Matsuda Index | Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG*FI)*(FPG+PG30*2+PG60*2+PG90*2+PG120)/8*(FPI+PI30*2+PI60*2+PI90*2+PI)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60,90, and 120 minutes after oral glucose load; PI30,60,90, and 120=plasma insulin levels sampled at 30,60,90, and 120 minutes after the oral glucose load | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Body Composition | Fat mass and lean mass were measured by dual energy X-ray absorptiometry (DEXA) at baseline and at the end of the 4 week treatment period | 4 weeks |
| Changes in Adipose Tissue Gene Expression |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William J Bremner, MD, PhD | University of Washington | Study Chair |
| Stephanie T Page, MD, PhD | University of Washington | Study Director |
| Katya Rubinow, MD | 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 |
|---|---|---|---|
| 16871273 | Background | Flegal KM. Excess deaths associated with obesity: cause and effect. Int J Obes (Lond). 2006 Aug;30(8):1171-2. doi: 10.1038/sj.ijo.0803313. No abstract available. | |
| 15579737 | Background | Araujo AB, O'Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004 Dec;89(12):5920-6. doi: 10.1210/jc.2003-031719. |
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116 subjects were screened, 63 subjects didn't meet study inclusion/exclusion criteria or they withdrew consent prior to group assignment, and 3 subjects withdrew prior to the baseline visit.
Recruitment period: 06/01/13-11/30/2014 Location: University/Medical Center Flyers, newspaper ads, online postings
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| ID | Title | Description |
|---|---|---|
| FG000 | Acyline & Placebo Gel & Placebo Pill | Acyline (300mcg/kg at Day 0 & week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Testosterone 1.62% gel | Drug | Transdermal Testosterone Gel (either 1.25g or 5g/d) for 4 weeks |
|
|
| Letrozole | Drug | Letrozole oral aromatase inhibitor 5mg daily for 4 weeks |
|
|
| Placebo gel (for Testosterone 1.62% gel) | Drug | placebo gel manufactured to mimic Testosterone 1.62% gel |
|
| Placebo pill (for Letrozole) | Drug | Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d |
|
We examined whether differences in lipoprotein lipase expression would be evident across study treatment groups. RNA was isolated from whole adipose tissue gene expression, and complementary DNA (cDNA) was synthesized from 1.5 ug of RNA per sample. Gene expression was measured by polymerase chain reaction (PCR) using predesigned TaqMan® Gene Expression Assays. Standard curves were included on each plate, so Ct values were converted to copy numbers of the target gene. Expression values were normalized to the geometric mean of the housekeeping genes phosphoglycerate kinase and 18s.
| 4 weeks |
| 19661128 | Background | Yeap BB, Chubb SA, Hyde Z, Jamrozik K, Hankey GJ, Flicker L, Norman PE. Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study. Eur J Endocrinol. 2009 Oct;161(4):591-8. doi: 10.1530/EJE-09-0348. Epub 2009 Aug 6. |
| 15687322 | Background | Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT. Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab. 2005 May;90(5):2618-23. doi: 10.1210/jc.2004-1158. Epub 2005 Feb 1. |
| 20368409 | Background | Li C, Ford ES, Li B, Giles WH, Liu S. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insulin resistance in men. Diabetes Care. 2010 Jul;33(7):1618-24. doi: 10.2337/dc09-1788. Epub 2010 Apr 5. |
| 18308111 | Background | Smith MR, Lee H, Fallon MA, Nathan DM. Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer. Urology. 2008 Feb;71(2):318-22. doi: 10.1016/j.urology.2007.08.035. |
| 16434464 | Background | Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006 Apr;91(4):1305-8. doi: 10.1210/jc.2005-2507. Epub 2006 Jan 24. |
| 9626114 | Background | Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD, Urban RJ. Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab. 1998 Jun;83(6):1886-92. doi: 10.1210/jcem.83.6.4892. |
| 17726076 | Background | Yialamas MA, Dwyer AA, Hanley E, Lee H, Pitteloud N, Hayes FJ. Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2007 Nov;92(11):4254-9. doi: 10.1210/jc.2007-0454. Epub 2007 Aug 28. |
| 21267541 | Background | Klimcakova E, Roussel B, Kovacova Z, Kovacikova M, Siklova-Vitkova M, Combes M, Hejnova J, Decaunes P, Maoret JJ, Vedral T, Viguerie N, Bourlier V, Bouloumie A, Stich V, Langin D. Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat. Diabetologia. 2011 Apr;54(4):876-87. doi: 10.1007/s00125-010-2014-3. Epub 2011 Jan 26. |
| 18838972 | Background | Odegaard JI, Chawla A. Mechanisms of macrophage activation in obesity-induced insulin resistance. Nat Clin Pract Endocrinol Metab. 2008 Nov;4(11):619-26. doi: 10.1038/ncpendmet0976. Epub 2008 Oct 7. |
| 21797916 | Background | Rubinow KB, Snyder CN, Amory JK, Hoofnagle AN, Page ST. Acute testosterone deprivation reduces insulin sensitivity in men. Clin Endocrinol (Oxf). 2012 Feb;76(2):281-8. doi: 10.1111/j.1365-2265.2011.04189.x. |
| 19008342 | Background | Ortega Martinez de Victoria E, Xu X, Koska J, Francisco AM, Scalise M, Ferrante AW Jr, Krakoff J. Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians. Diabetes. 2009 Feb;58(2):385-93. doi: 10.2337/db08-0536. Epub 2008 Nov 13. |
| 14679176 | Background | Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003 Dec;112(12):1796-808. doi: 10.1172/JCI19246. |
| 14663938 | Background | Xu HZ, Li Y, Zhao YF. [Diagnosis and treatment of osteopathic parathyroid adenoma]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2003 Nov;17(6):446-9. Chinese. |
| 18829989 | Background | Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 2008 Dec;57(12):3239-46. doi: 10.2337/db08-0872. Epub 2008 Oct 1. |
| 20936118 | Background | Rull A, Camps J, Alonso-Villaverde C, Joven J. Insulin resistance, inflammation, and obesity: role of monocyte chemoattractant protein-1 (or CCL2) in the regulation of metabolism. Mediators Inflamm. 2010;2010:326580. doi: 10.1155/2010/326580. Epub 2010 Sep 23. |
| 16613757 | Background | Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006 Mar;17(1):4-12. |
| 21483855 | Background | Chazenbalk G, Bertolotto C, Heneidi S, Jumabay M, Trivax B, Aronowitz J, Yoshimura K, Simmons CF, Dumesic DA, Azziz R. Novel pathway of adipogenesis through cross-talk between adipose tissue macrophages, adipose stem cells and adipocytes: evidence of cell plasticity. PLoS One. 2011 Mar 31;6(3):e17834. doi: 10.1371/journal.pone.0017834. |
| 20045727 | Background | Gilliver SC. Sex steroids as inflammatory regulators. J Steroid Biochem Mol Biol. 2010 May 31;120(2-3):105-15. doi: 10.1016/j.jsbmb.2009.12.015. Epub 2010 Jan 4. |
| 20352526 | Background | Cunningham M, Gilkeson G. Estrogen receptors in immunity and autoimmunity. Clin Rev Allergy Immunol. 2011 Feb;40(1):66-73. doi: 10.1007/s12016-010-8203-5. |
| 11532481 | Background | Bouman A, Moes H, Heineman MJ, de Leij LF, Faas MM. The immune response during the luteal phase of the ovarian cycle: increasing sensitivity of human monocytes to endotoxin. Fertil Steril. 2001 Sep;76(3):555-9. doi: 10.1016/s0015-0282(01)01971-9. |
| 19907077 | Background | Lai JJ, Lai KP, Chuang KH, Chang P, Yu IC, Lin WJ, Chang C. Monocyte/macrophage androgen receptor suppresses cutaneous wound healing in mice by enhancing local TNF-alpha expression. J Clin Invest. 2009 Dec;119(12):3739-51. doi: 10.1172/JCI39335. Epub 2009 Nov 9. |
| 17207634 | Background | Hildebrand F, Thobe BM, Hubbard WJ, Choudhry MA, Pape HC, Chaudry IH. Effects of 17beta-estradiol and flutamide on splenic macrophages and splenocytes after trauma-hemorrhage. Cytokine. 2006 Nov;36(3-4):107-14. doi: 10.1016/j.cyto.2006.11.002. Epub 2007 Jan 4. |
| 20427482 | Background | Qiu Y, Yanase T, Hu H, Tanaka T, Nishi Y, Liu M, Sueishi K, Sawamura T, Nawata H. Dihydrotestosterone suppresses foam cell formation and attenuates atherosclerosis development. Endocrinology. 2010 Jul;151(7):3307-16. doi: 10.1210/en.2009-1268. Epub 2010 Apr 28. |
| 18003947 | Background | Rettew JA, Huet-Hudson YM, Marriott I. Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod. 2008 Mar;78(3):432-7. doi: 10.1095/biolreprod.107.063545. Epub 2007 Nov 14. |
| 21900603 | Background | Ribas V, Drew BG, Le JA, Soleymani T, Daraei P, Sitz D, Mohammad L, Henstridge DC, Febbraio MA, Hewitt SC, Korach KS, Bensinger SJ, Hevener AL. Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16457-62. doi: 10.1073/pnas.1104533108. Epub 2011 Sep 7. |
| 18089690 | Background | Kratz M, Purnell JQ, Breen PA, Thomas KK, Utzschneider KM, Carr DB, Kahn SE, Hughes JP, Rutledge EA, Van Yserloo B, Yukawa M, Weigle DS. Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy. J Clin Endocrinol Metab. 2008 Mar;93(3):959-66. doi: 10.1210/jc.2007-0197. Epub 2007 Dec 18. |
| 12107227 | Background | Herbst KL, Anawalt BD, Amory JK, Bremner WJ. Acyline: the first study in humans of a potent, new gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab. 2002 Jul;87(7):3215-20. doi: 10.1210/jcem.87.7.8675. |
| 15579744 | Background | Herbst KL, Coviello AD, Page S, Amory JK, Anawalt BD, Bremner WJ. A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men. J Clin Endocrinol Metab. 2004 Dec;89(12):5959-65. doi: 10.1210/jc.2003-032123. |
| 15611571 | Background | Page ST, Herbst KL, Amory JK, Coviello AD, Anawalt BD, Matsumoto AM, Bremner WJ. Testosterone administration suppresses adiponectin levels in men. J Androl. 2005 Jan-Feb;26(1):85-92. |
| 8637535 | Background | Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996 Jul 4;335(1):1-7. doi: 10.1056/NEJM199607043350101. |
| 8855834 | Background | Tricker R, Casaburi R, Storer TW, Clevenger B, Berman N, Shirazi A, Bhasin S. The effects of supraphysiological doses of testosterone on angry behavior in healthy eugonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3754-8. doi: 10.1210/jcem.81.10.8855834. |
| 15562020 | Background | Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005 Feb;90(2):678-88. doi: 10.1210/jc.2004-1184. Epub 2004 Nov 23. |
| 21441069 | Background | Cuzick J, DeCensi A, Arun B, Brown PH, Castiglione M, Dunn B, Forbes JF, Glaus A, Howell A, von Minckwitz G, Vogel V, Zwierzina H. Preventive therapy for breast cancer: a consensus statement. Lancet Oncol. 2011 May;12(5):496-503. doi: 10.1016/S1470-2045(11)70030-4. |
| 12519853 | Background | Leder BZ, LeBlanc KM, Schoenfeld DA, Eastell R, Finkelstein JS. Differential effects of androgens and estrogens on bone turnover in normal men. J Clin Endocrinol Metab. 2003 Jan;88(1):204-10. doi: 10.1210/jc.2002-021036. |
| 19844120 | Background | Belgorosky A, Guercio G, Pepe C, Saraco N, Rivarola MA. Genetic and clinical spectrum of aromatase deficiency in infancy, childhood and adolescence. Horm Res. 2009;72(6):321-30. doi: 10.1159/000249159. Epub 2009 Oct 21. |
| 19139016 | Background | Campbell KL, Makar KW, Kratz M, Foster-Schubert KE, McTiernan A, Ulrich CM. A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk. Cancer Prev Res (Phila). 2009 Jan;2(1):37-42. doi: 10.1158/1940-6207.CAPR-08-0073. |
| 17957034 | Background | Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E15-26. doi: 10.1152/ajpendo.00645.2007. Epub 2007 Oct 23. |
| 20148674 | Background | Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219-46. doi: 10.1146/annurev-physiol-021909-135846. |
| 29793828 | Derived | Rubinow KB, Vaisar T, Chao JH, Heinecke JW, Page ST. Sex steroids mediate discrete effects on HDL cholesterol efflux capacity and particle concentration in healthy men. J Clin Lipidol. 2018 Jul-Aug;12(4):1072-1082. doi: 10.1016/j.jacl.2018.04.013. Epub 2018 Apr 30. |
| 27482750 | Derived | Chao J, Rubinow KB, Kratz M, Amory JK, Matsumoto AM, Page ST. Short-Term Estrogen Withdrawal Increases Adiposity in Healthy Men. J Clin Endocrinol Metab. 2016 Oct;101(10):3724-3731. doi: 10.1210/jc.2016-1482. Epub 2016 Aug 2. |
| FG001 | Acyline & Testosterone Gel 1.25g/d & Placebo Pill | Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d |
| FG002 | Acyline & Testosterone Gel 5g/d & Placebo Pill | Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d |
| FG003 | Acyline & Testosterone Gel & Letrozole | Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Acyline & Placebo Gel & Placebo Pill | Acyline (300mcg/kg at Day 0 & week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d |
| BG001 | Acyline & Testosterone Gel 1.25g/d & Placebo Pill | Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d |
| BG002 | Acyline & Testosterone Gel 5g/d & Placebo Pill | Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d |
| BG003 | Acyline & Testosterone Gel & Letrozole | Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
| ||||||||||||||||
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m2 |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kg |
| |||||||||||||||
| Fasting Glucose | Mean | Standard Deviation | mg/dL |
| |||||||||||||||
| Percentage Body Fat | Mean | Standard Deviation | %total body mass |
| |||||||||||||||
| Percentage Lean Mass | Mean | Standard Deviation | %total body mass |
|
| 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 | Insulin Sensitivity Quantified by Matsuda Index | Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG*FI)*(FPG+PG30*2+PG60*2+PG90*2+PG120)/8*(FPI+PI30*2+PI60*2+PI90*2+PI)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60,90, and 120 minutes after oral glucose load; PI30,60,90, and 120=plasma insulin levels sampled at 30,60,90, and 120 minutes after the oral glucose load | Of the 53 subjects who attended the baseline study visit, 2 withdrew from the study and 1 was discontinued due to a protocol violation. 50 subjects completed the week 10 study visit. Of these, 5 subjects were excluded from the final analyses; 1 was found to have undiagnosed diabetes, and 4 subjects were excluded due to study drug non-adherence. | Posted | Median | Inter-Quartile Range | units on a scale | 4 weeks |
|
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| Secondary | Changes in Body Composition | Fat mass and lean mass were measured by dual energy X-ray absorptiometry (DEXA) at baseline and at the end of the 4 week treatment period | Posted | Mean | Standard Deviation | kg | 4 weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in Adipose Tissue Gene Expression | We examined whether differences in lipoprotein lipase expression would be evident across study treatment groups. RNA was isolated from whole adipose tissue gene expression, and complementary DNA (cDNA) was synthesized from 1.5 ug of RNA per sample. Gene expression was measured by polymerase chain reaction (PCR) using predesigned TaqMan® Gene Expression Assays. Standard curves were included on each plate, so Ct values were converted to copy numbers of the target gene. Expression values were normalized to the geometric mean of the housekeeping genes phosphoglycerate kinase and 18s. | Subjects were included who had adipose tissue samples available from both baseline and week 4 (end-of-treatment) visits. | Posted | Mean | Standard Deviation | gene copy number per ng RNA | 4 weeks |
|
Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended.
There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of >15% was used for reported events.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Acyline & Placebo Gel & Placebo Pill | Acyline (300mcg/kg at Day 0 & week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Placebo gel (for Testosterone 1.62% gel): placebo gel manufactured to mimic Testosterone 1.62% gel Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d | 2 | 13 | 9 | 13 | ||
| EG001 | Acyline & Testosterone Gel 1.25g/d & Placebo Pill | Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d | 1 | 14 | 9 | 14 | ||
| EG002 | Acyline & Testosterone Gel 5g/d & Placebo Pill | Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Placebo pill (for Letrozole): Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d | 0 | 13 | 7 | 13 | ||
| EG003 | Acyline & Testosterone Gel & Letrozole | Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks | 0 | 13 | 10 | 13 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac Arrthymia | Cardiac disorders | Non-systematic Assessment |
| ||
| Abnormal Liver enzyme (AST & ALT) levels | Hepatobiliary disorders | Non-systematic Assessment |
| ||
| Elevated PSA level | Endocrine disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hot Flashes | Endocrine disorders | Non-systematic Assessment |
| ||
| Low libido | Endocrine disorders | Non-systematic Assessment |
| ||
| Erectile Dysfunction | Nervous system disorders | Non-systematic Assessment |
| ||
| Low Energy | General disorders | Non-systematic Assessment |
| ||
| Irritability | General disorders | Non-systematic Assessment |
| ||
| Decreased testes size | Endocrine disorders | Non-systematic Assessment |
| ||
| Fatigue | General disorders | Non-systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Katya Rubinow | University of Washington | 206-7543-3470 | rubinow@uw.edu |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| D008659 | Metabolic Diseases |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C109238 | acyline |
| D013739 | Testosterone |
| D005782 | Gels |
| D000077289 | Letrozole |
| ID | Term |
|---|---|
| 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 |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG003 | Acyline & Testosterone Gel & Letrozole | Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks Acyline: 300 mcg/mL administered subcutaneously (at Day 0, Week 2) Testosterone 1.62% gel: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks |
|
|
|
| Acyline + Testosterone Gel (5g/d) + Placebo Pills |
Acyline (300 mcg/kg, subcutaneous injection at weeks 0, 2) + testosterone gel administered daily + daily placebo pills. This group was intended to have normal, physiologic levels of serum testosterone and estradiol. |
| OG003 | Acyline + Testosterone Gel (5g/d) + Letrozole | Acyline (300 mcg/kg, subcutaneous injection at weeks 0, 2) + testosterone gel administered daily + daily letrozole (pills). This group was intended to have normal levels of serum testosterone with selective estrogen deficiency. |
|
|
|