drugset / Trial / NCT04288427
5-Alpha Reductase 2 as a Marker of Resistance to 5ARI Therapy
Recruiting
120 enrolled
Beth Israel Deaconess Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · collab
NaSingle-groupOpen-labelTreatment
Summary
The study is being conducted to learn why some patients with Benign Prostatic Hyperplasia (BPH) do not respond to a commonly used treatment drug, Finasteride. The hope is to find ways to predict which patients will not respond to Finasteride so that, in the future, these patients can be identified prior to offering this treatment and they can be offered alternative treatment strategies in its place. The aim is to see if noninvasive techniques such as MRI can detect inflammation of the prostate to assist with early detection of those who will and who will not respond to Finasteride.
Timeline
- Start
- 2020-09-25
- Primary completion
- 2026-06-30
- Completion
- 2026-11-30
Publications
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- Background Saigal CS, Joyce G. Economic costs of benign prostatic hyperplasia in the private sector. J Urol. 2005 Apr;173(4):1309-13. doi: 10.1097/01.ju.0000152318.79184.6f.
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- Background McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, Albertsen P, Roehrborn CG, Nickel JC, Wang DZ, Taylor AM, Waldstreicher J. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med. 1998 Feb 26;338(9):557-63. doi: 10.1056/NEJM199802263380901.
- Background McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg LM Jr, Clarke HS, Crawford ED, Diokno A, Foley JP, Foster HE, Jacobs SC, Kaplan SA, Kreder KJ, Lieber MM, Lucia MS, Miller GJ, Menon M, Milam DF, Ramsdell JW, Schenkman NS, Slawin KM, Smith JA; Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056/NEJMoa030656.
- Background Roehrborn CG, Oyarzabal Perez I, Roos EP, Calomfirescu N, Brotherton B, Wang F, Palacios JM, Vasylyev A, Manyak MJ. Efficacy and safety of a fixed-dose combination of dutasteride and tamsulosin treatment (Duodart((R)) ) compared with watchful waiting with initiation of tamsulosin therapy if symptoms do not improve, both provided with lifestyle advice, in the management of treatment-naive men with moderately symptomatic benign prostatic hyperplasia: 2-year CONDUCT study results. BJU Int. 2015 Sep;116(3):450-9. doi: 10.1111/bju.13033. Epub 2015 Jan 29.
- Background Bautista OM, Kusek JW, Nyberg LM, McConnell JD, Bain RP, Miller G, Crawford ED, Kaplan SA, Sihelnik SA, Brawer MK, Lepor H. Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. Control Clin Trials. 2003 Apr;24(2):224-43. doi: 10.1016/s0197-2456(02)00263-5.
- Background Kaplan SA, Lee JY, Meehan AG, Kusek JW; MTOPS Research Group. Long-term treatment with finasteride improves clinical progression of benign prostatic hyperplasia in men with an enlarged versus a smaller prostate: data from the MTOPS trial. J Urol. 2011 Apr;185(4):1369-73. doi: 10.1016/j.juro.2010.11.060. Epub 2011 Feb 22.
- Background Wang K, Fan DD, Jin S, Xing NZ, Niu YN. Differential expression of 5-alpha reductase isozymes in the prostate and its clinical implications. Asian J Androl. 2014 Mar-Apr;16(2):274-9. doi: 10.4103/1008-682X.123664.
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- Background Livingstone DE, Barat P, Di Rollo EM, Rees GA, Weldin BA, Rog-Zielinska EA, MacFarlane DP, Walker BR, Andrew R. 5alpha-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents. Diabetes. 2015 Feb;64(2):447-58. doi: 10.2337/db14-0249. Epub 2014 Sep 19.
- Background Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol. 2012;2012:530121. doi: 10.1155/2012/530121. Epub 2011 Dec 25.
- Background Stiles AR, Russell DW. SRD5A3: A surprising role in glycosylation. Cell. 2010 Jul 23;142(2):196-8. doi: 10.1016/j.cell.2010.07.003.
- Background Ge R, Wang Z, Bechis SK, Otsetov AG, Hua S, Wu S, Wu CL, Tabatabaei S, Olumi AF. DNA methyl transferase 1 reduces expression of SRD5A2 in the aging adult prostate. Am J Pathol. 2015 Mar;185(3):870-82. doi: 10.1016/j.ajpath.2014.11.020. Epub 2015 Feb 17.
- Background Bechis SK, Otsetov AG, Ge R, Olumi AF. Personalized medicine for the management of benign prostatic hyperplasia. J Urol. 2014 Jul;192(1):16-23. doi: 10.1016/j.juro.2014.01.114. Epub 2014 Feb 25.
- Background Baylin SB, Jones PA. A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011 Sep 23;11(10):726-34. doi: 10.1038/nrc3130.
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- Background Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, Marotz C, Giannopoulou E, Chakravarthi BV, Varambally S, Tomlins SA, Nanus DM, Tagawa ST, Van Allen EM, Elemento O, Sboner A, Garraway LA, Rubin MA, Demichelis F. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 2016 Mar;22(3):298-305. doi: 10.1038/nm.4045. Epub 2016 Feb 8.
- Background Bechis SK, Otsetov AG, Ge R, Wang Z, Vangel MG, Wu CL, Tabatabaei S, Olumi AF. Age and Obesity Promote Methylation and Suppression of 5alpha-Reductase 2: Implications for Personalized Therapy of Benign Prostatic Hyperplasia. J Urol. 2015 Oct;194(4):1031-7. doi: 10.1016/j.juro.2015.04.079. Epub 2015 Apr 25.
- Background Austin DC, Strand DW, Love HL, Franco OE, Grabowska MM, Miller NL, Hameed O, Clark PE, Matusik RJ, Jin RJ, Hayward SW. NF-kappaB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance. Prostate. 2016 Aug;76(11):1004-18. doi: 10.1002/pros.23195. Epub 2016 May 16.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Finasteride | Small molecule | — | — |