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Status unknownNCT04456530Updated Aug 31, 2021

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

A Phase 2/3 interventional study of Aveed 750 MG in 3 ML IM Injection and Normal Saline 3 ML IM Injection in Muscle Atrophy, Surgery and Knee Injuries and Disorders, sponsored by The Stone Research Foundation for Sports Medicine and Arthritis. Status unknown at 1 site in United States. Open to male participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-08-31.

Sponsored by The Stone Research Foundation for Sports Medicine and Arthritis · Phase 2/3, Interventional, and Prevention

The sponsor has not verified this record recently (last verified Aug 2021), so the status shown — last known as Enrolling by invitation — may be out of date.
Phase
Phase 2/3
Study type
Interventional
Enrollment
15
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
Male
01

Study 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.

Read the detailed 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.

02

Conditions studied

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

Keywords

  • Surgery
  • Testosterone
  • Muscle atrophy
  • Post-operative rehabilitation
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
15 participants (estimated)

Study arms

  • Experimental
    Testosterone Group

    Participants receiving two IM Testosterone injections.

    Drug: Aveed 750 MG in 3 ML IM Injection

  • Placebo comparator
    Control Group

    Participants receiving two IM Normal Saline Injections.

    Other: Normal Saline 3 ML IM Injection

Interventions

  • DrugAveed 750 MG in 3 ML IM Injection

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

  • OtherNormal Saline 3 ML IM Injection

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

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Pre-operative and 1, 3, and 6 months post-operative

  2. 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.

    Time frame: Pre-operative and 1, 3, and 6 months post-operative

Secondary outcomes

  1. Change in Knee Pain and Function Survey, KOOS

    Evaluate the knee pain and function of subjects as measures by the KOOS assessment. Sections: 1. Pain 2. Symptoms 3. Activities of Daily Living 4. Sports and Recreation 5. 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.

    Time frame: Pre-operative and 1, 3, and 6 months post-operative

Other outcomes

  1. Change in serum cortisol (mcg/dL) levels

    Laboratory blood analysis of cortisol will be performed for therapeutic assessment and safety.

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

  2. Change in serum testosterone (ng/dL) levels

    Laboratory blood analysis of testosterone will be performed for therapeutic assessment and safety.

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

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

    Laboratory blood analysis of PSA will be performed for therapeutic assessment and safety.

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

  4. Change in serum hepatic function panel (mg/dL) levels

    Laboratory blood analysis of HFP will be performed for therapeutic assessment and safety.

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

  5. Change in complete blood count with differential levels

    Laboratory blood analysis CBC w/ diff will be performed for therapeutic assessment and safety.

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

06

Study locations

1 site
  • Stone Research Foundation
    San Francisco, California 94123, United States
07

References and documents

Publications

  • 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. PubMed 19707253 ↗
  • 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. PubMed 984911 ↗
  • 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. PubMed 9353686 ↗
  • 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. PubMed 25358592 ↗
  • 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. PubMed 25278072 ↗
  • 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. PubMed 26268693 ↗
  • Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med. 2004;34(8):513-54. doi: 10.2165/00007256-200434080-00003. PubMed 15248788 ↗
  • 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. PubMed 9604196 ↗
  • 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. PubMed 1285753 ↗
  • 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. PubMed 12366624 ↗
  • 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. PubMed 2917954 ↗
  • 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. PubMed 15827765 ↗
  • 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. PubMed 28840147 ↗
08

Registry details

Key details

Study ID
NCT04456530
Lead sponsor
The Stone Research Foundation for Sports Medicine and Arthritis
Responsible party
Sponsor
First posted
Jul 2, 2020
Start date
May 8, 2020
Primary completion
Dec 30, 2021 (estimated)
Completion
Jun 30, 2022 (estimated)
Last update
Aug 31, 2021

Study contacts

Mani Vessal, Ph.D.
study director · Stone Research Foundation

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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