Evaluation of rGH Therapy to Prevent Muscle Atrophy in Patients With ACL Tears

NCT02420353 | Completed Phase 2 Results DMC

• 2 other identifiers: HUM00087702IND Exemption 123189
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Rupture of Anterior Cruciate Ligament

Keywords

muscle atrophy; growth hormone; ACL tear

Outcome Measures

Primary Outcomes (1)

• Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op

  Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

  at 26 wks post-op

Secondary Outcomes (43)

• Normative Isokinetic Extension (Nm) at Pre-op (Baseline)

  at pre-op (baseline)

• Normative Isokinetic Flexion (Nm) at Pre-op (Baseline)

  at pre-op (baseline)

• Normative Isokinetic Flexion (Nm) at 26 Weeks Post-op

  at 26 weeks post-op

• Normative Isometric Extension (Nm) at Pre-op (Baseline)

  at pre-op (baseline)

• Normative Isometric Extension (Nm) at 26 Weeks Post-op

  at 26 weeks post-op

Study Arms (2)

Somatropin

ACTIVE COMPARATOR

Somatropin of rDNA origin

Drug: Somatropin

Placebo

PLACEBO COMPARATOR

A placebo vehicle that contains somatropin diluent but no active hormone.

Drug: Placebo

Interventions

Somatropin DRUG

GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.

Somatropin

Placebo DRUG

A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan: lead
• Hospital for Special Surgery, New York: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (5)

• Boesen AP, Dideriksen K, Couppe C, Magnusson SP, Schjerling P, Boesen M, Kjaer M, Langberg H. Tendon and skeletal muscle matrix gene expression and functional responses to immobilisation and rehabilitation in young males: effect of growth hormone administration. J Physiol. 2013 Dec 1;591(23):6039-52. doi: 10.1113/jphysiol.2013.261263. Epub 2013 Sep 30.

  PMID: 24081158 BACKGROUND

• Surya S, Horowitz JF, Goldenberg N, Sakharova A, Harber M, Cornford AS, Symons K, Barkan AL. The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects. J Clin Endocrinol Metab. 2009 Aug;94(8):2828-34. doi: 10.1210/jc.2009-0638. Epub 2009 May 26.

  PMID: 19470622 BACKGROUND

• 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.

  PMID: 23739685 BACKGROUND

• Gelato M, McNurlan M, Freedland E. Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment. Clin Ther. 2007 Nov;29(11):2269-88. doi: 10.1016/j.clinthera.2007.11.004.

  PMID: 18158071 BACKGROUND

• 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.

  PMID: 32452208 DERIVED

MeSH Terms

Conditions

Anterior Cruciate Ligament Injuries; Muscular Atrophy

Interventions

Human Growth Hormone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Please consult the full manuscript or contact the study PI for any questions about study results. Additional clinical trials must be conducted before definitive conclusions can be made.

Results Point of Contact

• Title: Dr. Christopher Mendias
• Organization: Hopsital For Special Surgery and University of Michigan

mendiasc@hss.edu

212-249-2373

Study Officials

• Christopher L Mendias, PhD, ATC

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 9, 2015
• First Posted: April 17, 2015
• Study Start: May 1, 2015
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: January 6, 2020
• Results First Posted: January 6, 2020

Record last verified: 2019-12

Locations

US (1)