Peri-Operative Testosterone Administration in Primary Total Hip Arthroplasty

Обзор

It is often observed that patients following total hip replacement have a hard time with rehabilitation, as patients commonly lose muscle mass and strength around the surgical site. The goal of this study is to learn if giving patients testosterone around their hip surgery can prevent them from losing muscle mass, as well as to see if it will improve their outcomes after surgery. The main question this study aims to answer is: Will perioperative testosterone administration increase lean mass in addition to improving functional and clinical patient reported outcomes greater than placebo? Researchers will compare patients who were administered testosterone to standard of care (no administration of testosterone) to see if there is a difference in their recovery and outcomes. Participants will be given either testosterone or saline for eight weeks beginning two weeks prior to surgery. Participants will have to answer questionnaires on how they are doing, as well as will do other testing during this time.

Подробное описание

The purpose of this double blinded, randomized controlled trial is to determine if weekly intramuscular testosterone administration can prevent short-term catabolic loss of lean mass in patients undergoing total hip arthroplasty in addition to improving functional and patient-reported outcome scores. It is hypothesized that perioperative testosterone administration will increase lean mass in addition to improving functional and clinical patient reported outcomes greater than placebo. This is the first study, to our knowledge, investigating the effects of perioperative testosterone administration on male patients undergoing total hip arthroplasty.

Participants will be randomly assigned to receive testosterone or placebo treatment. This will be performed using a simple 1:1 randomization and will be provided to the study's designated team member who is not associated with the study, to be referred to as the pharmacist. Except for the statistician performing the randomization and the pharmacist, all individuals involved - including the investigators, study team, surgeon, physical therapist, and patient - will be blinded to the assigned treatment.

Informed consent documentation will include an in-depth discussion of the possible, but uncommon, risks of testosterone including allergic reactions, liver function test alterations, breast tenderness, hair growth or loss, polycythemia, and mood or mental changes. These potential adverse events will be monitored during all study visits.

The testosterone group will receive a 200mg dose of intramuscular testosterone cypionate (also known as Nandrolone) weekly for 8 weeks beginning 2 weeks prior to surgery. The 200 mg per week regimen is being selected with the goal of being a dose sufficient to provide an anabolic stimulus, and low enough to minimize potential adverse effects \[10-13\]. Control participants in the placebo group will follow the same schedule of injections with an intramuscular dose of saline instead of testosterone. All participants will follow a structured, standard of care, rehabilitation protocol within one week of surgery. All participants will follow a structured, standard of care, rehabilitation protocol within one week of surgery. Common markers of endocrine function will be monitored for potential systemic side effects of testosterone using blood analysis of pituitary hormones including luteinizing hormone (LH) and follicle stimulating hormone (FSH), prostate-specific antigen (PSA), alanine aminotransferase (ALT), hematocrit, hemoglobin, and white blood cell at 2 weeks preoperatively, the day of surgery, and then 2 weeks, 6 weeks, 3 months, and 2 years postoperatively.

Вмешательства

• Препарат Nandrolone decanoate
  Nandrolone will be administered to the testosterone group, specifically a 200mg dose weekly for 8 weeks beginning 2 weeks prior to surgery.
• Препарат Saline
  Saline will be administered to the saline group, specifically a 200mg dose weekly for 8 weeks beginning 2 weeks prior to surgery.

Первичные конечные точки

• modified Harris Hip Score [Срок оценки: 2 years]

Вторичные конечные точки (3)

• HOS-SSS [Срок оценки: 2 years]
• iHOT-12 [Срок оценки: 2 years]
• Total lean body mass [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Male patients over the age of 18 with a diagnosis of osteoarthritis or dysplasia that are undergoing total hip replacement will be recruited to the study and screened for eligibility. Inclusion criteria include clinical diagnosis of osteoarthritis or dysplasia, age 18 and older, and hypogonadism, defined as a testosterone level \<300ng/dL or clinical signs of hypogonadism including reduced muscle mass and strength, decreased libido, erectile dysfunction, loss of body hair, low bone mineral density, infertility, gynecomastia, or incomplete or delayed sexual development.

Критерии исключения

• Major exclusion criteria include previous arthroplasty of the affected hip, previous spine surgery, a past medical history significant for allergy to testosterone, prostate cancer, PSA \>4 ng/ml, breast cancer, polycythemia, diabetes mellitus with a HbA1c \> 7, BMI \<18 or \> 40, and preoperative motion or strength limitations that will affect postoperative rehabilitation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1172-81. doi: 10.1152/ajpendo.2001.281.6.E1172. PMID 11701431
• Bhasin S, Storer TW, Javanbakht M, Berman N, Yarasheski KE, Phillips J, Dike M, Sinha-Hikim I, Shen R, Hays RD, Beall G. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA. 2000 Feb 9;283(6):763-70. doi: 10.1001/jama.283.6.763. PMID 10683055
• Basaria S, Wahlstrom JT, Dobs AS. Clinical review 138: Anabolic-androgenic steroid therapy in the treatment of chronic diseases. J Clin Endocrinol Metab. 2001 Nov;86(11):5108-17. doi: 10.1210/jcem.86.11.7983. PMID 11701661
• Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul 8;363(2):109-22. d PMID 20592293
• Sattler FR, Castaneda-Sceppa C, Binder EF, Schroeder ET, Wang Y, Bhasin S, Kawakubo M, Stewart Y, Yarasheski KE, Ulloor J, Colletti P, Roubenoff R, Azen SP. Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab. 2009 Jun;94(6):1991-2001. doi: 10.1210/jc.2008-2338. Epub 2009 Mar 17. PMID 19293261
• 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. PMID 8637535
• Amory JK, Chansky HA, Chansky KL, Camuso MR, Hoey CT, Anawalt BD, Matsumoto AM, Bremner WJ. Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. J Am Geriatr Soc. 2002 Oct;50(10):1698-701. doi: 10.1046/j.1532-5415.2002.50462.x. PMID 12366624
• Wu B, Lorezanza D, Badash I, Berger M, Lane C, Sum JC, Hatch GF 3rd, Schroeder ET. Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial. Orthop J Sports Med. 2017 Aug 9;5(8):2325967117722794. doi: 10.1177/2325967117722794. eCollection 2017 Aug. PMID 28840147

Идентификаторы

NCT: NCT06608914 · AHI-005

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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