Clinical trial NCT02420353: Evaluation of rGH Therapy to Prevent Muscle Atrophy in Patients With ACL Tears
Official title: Evaluation of Recombinant Growth Hormone Therapy to Prevent Muscle Atrophy in Patients With Anterior Cruciate Ligament Tears
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rupture of Anterior Cruciate Ligament
Keywords: muscle atrophy
growth hormone
ACL tear
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Hospital for Special Surgery, New York
First posted: 2015-04-17
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Anterior cruciate ligament (ACL) tears are among the most frequent traumatic knee injuries that occur in physically active individuals. Despite advances in minimally invasive surgical reconstruction techniques and aggressive rehabilitation, this atrophy and loss of strength can persist even after patients return to full activity and can place them at considerable risk for re-injury and developing osteoarthritis (OA). The design of new therapeutic interventions to prevent muscle atrophy is needed to advance the care of patients who suffer from ACL injuries. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis plays an important role in promoting muscle growth and protecting muscle from atrophy. While GH therapy has shown promise in protecting immobilized muscle from various models of disuse atrophy, it remains unknown whether GH can help to restore strength and protect against the loss in strength that occurs after ACL tear. GH therapy may help to accelerate the safe return to play of patients that suffer ACL tears, and help to prevent the long-term OA and reduction in quality of life that occur after these traumatic knee injuries.


Eligibility criteria: Inclusion Criteria:

* Males between the ages of 18 and 35
* Have acute unilateral complete ACL tears with or without bucket handle medial meniscus tears that occurred within the past 6 months
* Consent to undergo an ACL reconstruction by an orthopaedic surgeon using a patellar tendon or hamstring autograft
* Will be performing supervised post-operative rehabilitation at UMHS MedSport at Dominos Farms

Exclusion Criteria:

* Patients who are undergoing a revision ACL reconstruction
* Had a previous injury to the involved knee
* Have an allergy to recombinant GH
* Have a BMI\<20 or \>35
* Have a growth disorder of bones or connective tissue, type 1 diabetes mellitus, type 2 diabetes mellitus, or who have a history of carpal tunnel syndrome, trigger finger, myopathy, cancer, endocrine disorder, hypertension or rheumatologic disorder.
* Systolic blood pressure \>140mm Hg or diastolic blood pressure \>90mm Hg, or with resting heart rate \>110 BPM or \<40 BPM at screening.
* Additionally, because GH is currently listed as a banned substance by the World Anti-Doping Agency (WADA), National Collegiate Athletics Association (NCAA) and most professional sports agencies, we will exclude patients who are current collegiate, professional or elite athletes.

Primary outcomes:
measure: Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op
timeFrame: at 26 wks post-op
Secondary outcomes:
measure: Normative Isokinetic Extension (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Normative Isokinetic Flexion (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Normative Isokinetic Flexion (Nm) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Normative Isometric Extension (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Normative Isometric Extension (Nm) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Normative Isometric Flexion (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Normative Isometric Flexion (Nm) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Absolute Isokinetic Extension (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Absolute Isokinetic Extension (Nm) at 26 wk Post-op
timeFrame: at 26 wk post-op
measure: Absolute Isokinetic Flexion (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Absolute Isokinetic Flexion (Nm) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Absolute Isometric Extension (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Absolute Isometric Extension (Nm) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Absolute Isometric Flexion (Nm) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Absolute Isometric Flexion (Nm) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: VR12 Health Survey: Physical Health Summary Measure Score at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: VR12 Health Survey: Physical Health Summary Measure Score at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: VR12 Health Survey: Mental Health Summary Measure Score at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: VR12 Health Survey: Mental Health Summary Measure Score at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: International Knee Document Committee (IKDC) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: International Knee Documentation Committee (IKDC) up to 26 wk Post-op
timeFrame: up to 26 wk post-op
measure: The Knee Injury and Osteoarthritis Outcome Score (KOOS): Patient Reported Outcome Measure: ADL at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: KOOS Patient Reported Outcome Measure: ADL at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: KOOS Patient Reported Outcome Measure: Pain at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: KOOS Patient Reported Outcome Measure: Pain at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: KOOS Patient Reported Outcome Measure: Quality of Life at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: KOOS Patient Reported Outcome Measure: Quality of Life at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: KOOS Patient Reported Outcome Measure: Sport and Recreation at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: KOOS Patient Reported Outcome Measure: Sports and Recreation at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: KOOS Patient Reported Outcome Measure: Symptoms at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: KOOS Patient Reported Outcome Measure: Symptoms at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Absolute Quadriceps Volume (L) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Absolute Quadricep Volume (L) at 26 Week Post-op
timeFrame: at 26 week post-op
measure: Absolute Hamstring Volume (L) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Absolute Hamstring Volume (L) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Normalized Quadriceps Volume (L) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Normalized Quadriceps Volume (L) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Normalized Hamstring Volume (L) at Pre-op (Baseline)
timeFrame: at pre-op (baseline)
measure: Normalized Hamstring Volume (L) at 26 Weeks Post-op
timeFrame: at 26 weeks post-op
measure: Insulin Like Growth Factor (IGF1) at -1 and 5 Weeks Post-op
timeFrame: Area under the curve between -1 and 5 weeks post-op
measure: Myostatin at -1 and 5 Weeks Post-op
timeFrame: Area under the curve between -1 and 5 weeks post-op
measure: MMP3 at -1 and 5 Weeks Post-op
timeFrame: Area under the curve between -1 and 5 weeks post-op
measure: Hyaluronic Acid at -1 and 5 Weeks Post-op
timeFrame: Area under the curve between -1 and 5 weeks post-op
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Christopher L Mendias, PhD, ATC
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Mendias CL, Lynch EB, Davis ME, Sibilsky Enselman ER, Harning JA, Dewolf PD, Makki TA, Bedi A. Changes in circulating biomarkers of muscle atrophy, inflammation, and cartilage turnover in patients undergoing anterior cruciate ligament reconstruction and rehabilitation. Am J Sports Med. 2013 Aug;41(8):1819-26. doi: 10.1177/0363546513490651. Epub 2013 Jun 5.
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citation: Mendias CL, Enselman ERS, Olszewski AM, Gumucio JP, Edon DL, Konnaris MA, Carpenter JE, Awan TM, Jacobson JA, Gagnier JJ, Barkan AL, Bedi A. The Use of Recombinant Human Growth Hormone to Protect Against Muscle Weakness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pilot, Randomized Placebo-Controlled Trial. Am J Sports Med. 2020 Jul;48(8):1916-1928. doi: 10.1177/0363546520920591. Epub 2020 May 26.