Use of Testosterone to Prevent Post-Surgical Muscle Loss - Pilot Study

NCT04456530 | Unknown Phase 2 FDA Drug

• 1 other identifier: SRF-030
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The loss of muscle mass post-surgery confounds recovery efforts and leads to a delay in patient's ability to return to activities. Although the use of testosterone in aging and chronic muscle loss has been investigated, this study could prove short-term use of testosterone efficacious in preventing muscle atrophy due to surgery. We hypothesize that by bracketing an indexed knee surgery with testosterone undecanoate injections, post-surgical quadriceps muscle loss may be minimized. Determination of the effect of intra-muscular (IM) testosterone injections in preventing quadriceps muscle loss are measured by serial MRI and manual measurements of quadriceps cross-section.

Conditions

Muscle Atrophy; Surgery; Knee Injuries and Disorders; Complication of Surgical Procedure; Trauma

Keywords

Surgery; Testosterone; Muscle atrophy; Post-operative rehabilitation

Outcome Measures

Primary Outcomes (2)

• Change in MRI Cross Sectional Area of the Quadriceps

  T1 Axial and Sagittal planes will be obtained using a ONI 1.0T extremity MRI. Axial Cross sectional Area (cm\^2) will be measured of the Quadriceps muscle.

  Pre-operative and 1, 3, and 6 months post-operative

• Change in Manual Measurements of the Quadriceps

  Manual measurement of the quadriceps muscle will be performed 8-cm proximal to the superior-patella using a standard cm measuring tape.

  Pre-operative and 1, 3, and 6 months post-operative

Secondary Outcomes (1)

• Change in Knee Pain and Function Survey, KOOS

  Pre-operative and 1, 3, and 6 months post-operative

Other Outcomes (5)

• Change in serum cortisol (mcg/dL) levels

  Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative

• Change in serum testosterone (ng/dL) levels

  Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative

• Change in serum prostate specific antigen (ng/mL) levels

  Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative

Study Arms (2)

Testosterone Group

EXPERIMENTAL

Participants receiving two IM Testosterone injections.

Drug: Aveed 750 MG in 3 ML IM Injection

Control Group

PLACEBO COMPARATOR

Participants receiving two IM Normal Saline Injections.

Other: Normal Saline 3 ML IM Injection

Interventions

Aveed 750 MG in 3 ML IM Injection DRUG

Participants in the Testosterone Group will receive two IM Aveed injections 1 month apart.

Testosterone Group

Normal Saline 3 ML IM Injection OTHER

Participants in the Control Group will receive two IM normal saline injections 1 month apart.

Control Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males age 18-65.
• Undergoing significant knee surgery such as partial/total knee replacement, ligament reconstruction, meniscus surgeries or articular cartilage paste grafting.

You may not qualify if:

• Men with carcinoma of the breast or known or suspected carcinoma of the prostate.
• Men with BMI \> 30 and Type I or II diabetes diagnosis
• Men prone to deep vein thrombosis or sleep apnea.
• Men with pre-existing hematocrit abnormalities.
• Men with pre-existing cardiac, renal, hepatic disease.
• Men who are taking insulin, medicines that decrease blood clotting or corticosteroids.
• Men with known hypersensitivity to testosterone undecanoate or any of its formulation ingredients (testosterone, refined castor oil, benzyl benzoate).
• Subject's unable or unwilling to comply with the protocol.
• Subject's unable to provide informed consent.
• Subject's unable to understand verbal and/or written English.

Sponsors & Collaborators

• The Stone Research Foundation for Sports Medicine and Arthritis: lead

Study Sites (1)

Stone Research Foundation

San Francisco, California, 94123, United States

Location

Related Publications (13)

• Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009 Jun;5(3):427-48. doi: 10.2147/tcrm.s3025. Epub 2009 Jun 22.

  PMID: 19707253 BACKGROUND

• Nicholas JJ, Taylor FH, Buckingham RB, Ottonello D. Measurement of circumference of the knee with ordinary tape measure. Ann Rheum Dis. 1976 Jun;35(3):282-4. doi: 10.1136/ard.35.3.282.

  PMID: 984911 BACKGROUND

• Arangio GA, Chen C, Kalady M, Reed JF 3rd. Thigh muscle size and strength after anterior cruciate ligament reconstruction and rehabilitation. J Orthop Sports Phys Ther. 1997 Nov;26(5):238-43. doi: 10.2519/jospt.1997.26.5.238.

  PMID: 9353686 BACKGROUND

• Marcon M, Ciritsis B, Laux C, Nanz D, Nguyen-Kim TD, Fischer MA, Andreisek G, Ulbrich EJ. Cross-sectional area measurements versus volumetric assessment of the quadriceps femoris muscle in patients with anterior cruciate ligament reconstructions. Eur Radiol. 2015 Feb;25(2):290-8. doi: 10.1007/s00330-014-3424-2. Epub 2014 Oct 31.

  PMID: 25358592 BACKGROUND

• Ruhdorfer AS, Dannhauer T, Wirth W, Cotofana S, Roemer F, Nevitt M, Eckstein F; OAI investigators. Thigh muscle cross-sectional areas and strength in knees with early vs knees without radiographic knee osteoarthritis: a between-knee, within-person comparison. Osteoarthritis Cartilage. 2014 Oct;22(10):1634-8. doi: 10.1016/j.joca.2014.06.002.

  PMID: 25278072 BACKGROUND

• Orgiu S, Lafortuna CL, Rastelli F, Cadioli M, Falini A, Rizzo G. Automatic muscle and fat segmentation in the thigh from T1-Weighted MRI. J Magn Reson Imaging. 2016 Mar;43(3):601-10. doi: 10.1002/jmri.25031. Epub 2015 Aug 13.

  PMID: 26268693 BACKGROUND

• Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med. 2004;34(8):513-54. doi: 10.2165/00007256-200434080-00003.

  PMID: 15248788 BACKGROUND

• Irrgang JJ, Ho H, Harner CD, Fu FH. Use of the International Knee Documentation Committee guidelines to assess outcome following anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc. 1998;6(2):107-14. doi: 10.1007/s001670050082.

  PMID: 9604196 BACKGROUND

• Brazier JE, Harper R, Jones NM, O'Cathain A, Thomas KJ, Usherwood T, Westlake L. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. BMJ. 1992 Jul 18;305(6846):160-4. doi: 10.1136/bmj.305.6846.160.

  PMID: 1285753 BACKGROUND

• 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 BACKGROUND

• Griggs RC, Kingston W, Jozefowicz RF, Herr BE, Forbes G, Halliday D. Effect of testosterone on muscle mass and muscle protein synthesis. J Appl Physiol (1985). 1989 Jan;66(1):498-503. doi: 10.1152/jappl.1989.66.1.498.

  PMID: 2917954 BACKGROUND

• Akima H, Furukawa T. Atrophy of thigh muscles after meniscal lesions and arthroscopic partial menisectomy. Knee Surg Sports Traumatol Arthrosc. 2005 Nov;13(8):632-7. doi: 10.1007/s00167-004-0602-9. Epub 2005 Apr 13.

  PMID: 15827765 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Muscular Atrophy; Knee Injuries; Disease; Wounds and Injuries

Interventions

Testosterone Propionate; Injections, Intramuscular; Saline Solution

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Leg Injuries; Pathologic Processes

Intervention Hierarchy (Ancestors)

Testosterone; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Mani Vessal, Ph.D.

  Stone Research Foundation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Both the participant and analyzing MRI Radiologist will be blind.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: July 2, 2020
• Study Start: May 8, 2020
• Primary Completion: December 30, 2021
• Study Completion: June 30, 2022
• Last Updated: August 31, 2021

Record last verified: 2021-08

Locations

US (1)