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

Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04456530
• Other study ID #: SRF-030
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• Start date: May 8, 2020
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2021
• Source: The Stone Research Foundation for Sports Medicine and Arthritis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is an in vivo study using serial IM testosterone undeconate injections in participants undergoing knee surgery with limited weight bearing post-operatively which includes partial/total knee replacement, ACL reconstruction/revision, meniscal allograft transplantation and articular cartilage paste grafting. The design is a randomized, controlled, double blind, longitudinal study of intra-muscular injections of testosterone versus saline control. Pre-operative and post-operative assessments will include: serial MRIs and manual measurements of quadriceps cross-section and knee pain and function survey, KOOS. Blood analysis will be performed for therapeutic assessment and safety. The participant will receive two testosterone undeconate injections, once during their pre-operative visit and once during their 1 month visit. Timing of assessments will be pre-operative, 1-4 days post-operative and 1, 3, and 6 months. Measurement of the control group versus experimental group at all time points may identify differences in participant response to testosterone injections.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 15
• Est. completion date: June 30, 2022
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Aveed 750 MG in 3 ML IM Injection
Participants in the Testosterone Group will receive two IM Aveed injections 1 month apart.

Other:
• Normal Saline 3 ML IM Injection
Participants in the Control Group will receive two IM normal saline injections 1 month apart.

Locations

Country	Name	City	State
United States	Stone Research Foundation	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
The Stone Research Foundation for Sports Medicine and Arthritis

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. Epub 2005 Apr 13. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2009 Jun 22. — View Citation

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. — View Citation

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. — View Citation

Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med. 2004;34(8):513-54. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in serum cortisol (mcg/dL) levels	Laboratory blood analysis of cortisol will be performed for therapeutic assessment and safety.	Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative
Other	Change in serum testosterone (ng/dL) levels	Laboratory blood analysis of testosterone will be performed for therapeutic assessment and safety.	Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative
Other	Change in serum prostate specific antigen (ng/mL) levels	Laboratory blood analysis of PSA will be performed for therapeutic assessment and safety.	Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative
Other	Change in serum hepatic function panel (mg/dL) levels	Laboratory blood analysis of HFP will be performed for therapeutic assessment and safety.	Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative
Other	Change in complete blood count with differential levels	Laboratory blood analysis CBC w/ diff will be performed for therapeutic assessment and safety.	Pre-operative, 1-4 days post-operative and 1 month and 3 months post-operative
Primary	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
Primary	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	Change in Knee Pain and Function Survey, KOOS	Evaluate the knee pain and function of subjects as measures by the KOOS assessment.; Sections: Pain; Symptoms; Activities of Daily Living; Sports and Recreation; Quality of Life; Scoring: Each subscale score is calculated independently. The mean score of the individual items of each subscale is calculated and divided by 4 (the highest possible score for a single answer option). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard.	Pre-operative and 1, 3, and 6 months post-operative

External Links

•   Aveed Prescribing Information