Rupture of Anterior Cruciate LigamentPhase 2NCT02420353
Evaluation of rGH Therapy to Prevent Muscle Atrophy in Patients With ACL Tears
A Phase 2 study testing Somatropin in people with Rupture of Anterior Cruciate Ligament, run by University of Michigan at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 years, men only
- Conditions the study is for
- Rupture of Anterior Cruciate Ligament
- What is being tested?
- Somatropin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Recombinant Growth Hormone Therapy to Prevent Muscle Atrophy in Patients With Anterior Cruciate Ligament Tears
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
- Being tested
- Somatropin, Placebo
- Keywords
- muscle atrophy, growth hormone, ACL tear
- Medical subject headings
- Anterior Cruciate Ligament Injuries, Muscular Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SomatropinDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Somatropin | Active comparator | Somatropin of rDNA origin Receives: Drug: Somatropin |
| Placebo | Placebo comparator | A placebo vehicle that contains somatropin diluent but no active hormone. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at 26 wks post-op
Secondary outcomes (43)
Normative Isokinetic Extension (Nm) at Pre-op (Baseline)
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.
Measured: at pre-op (baseline)
Normative Isokinetic Flexion (Nm) at Pre-op (Baseline)
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.
Measured: at pre-op (baseline)
Normative Isokinetic Flexion (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.
Measured: at 26 weeks post-op
Normative Isometric Extension (Nm) at Pre-op (Baseline)
Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º 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.
Measured: at pre-op (baseline)
Normative Isometric Extension (Nm) at 26 Weeks Post-op
Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º 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.
Measured: at 26 weeks post-op
Normative Isometric Flexion (Nm) at Pre-op (Baseline)
Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º 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.
Measured: at pre-op (baseline)
Normative Isometric Flexion (Nm) at 26 Weeks Post-op
Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º 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.
Measured: at 26 weeks post-op
Absolute Isokinetic Extension (Nm) at Pre-op (Baseline)
Absolute 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. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at pre-op (baseline)
Absolute Isokinetic Extension (Nm) at 26 wk Post-op
Absolute 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. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at 26 wk post-op
Absolute Isokinetic Flexion (Nm) at Pre-op (Baseline)
Absolute 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. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at pre-op (baseline)
Absolute Isokinetic Flexion (Nm) at 26 Weeks Post-op
Absolute 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. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at 26 weeks post-op
Absolute Isometric Extension (Nm) at Pre-op (Baseline)
Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at pre-op (baseline)
Absolute Isometric Extension (Nm) at 26 Weeks Post-op
Absolute Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at 26 weeks post-op
Absolute Isometric Flexion (Nm) at Pre-op (Baseline)
Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at pre-op (baseline)
Absolute Isometric Flexion (Nm) at 26 Weeks Post-op
Absolute Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Measured: at 26 weeks post-op
VR12 Health Survey: Physical Health Summary Measure Score at Pre-op (Baseline)
The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed PCS maximum: 72.11; minimum: 0.59.
Measured: at pre-op (baseline)
VR12 Health Survey: Physical Health Summary Measure Score at 26 Weeks Post-op
The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed PCS maximum: 72.11; minimum: 0.59.
Measured: at 26 weeks post-op
VR12 Health Survey: Mental Health Summary Measure Score at Pre-op (Baseline)
The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed MCS Maximum: 76.09; Minimum: -2.47.
Measured: at pre-op (baseline)
VR12 Health Survey: Mental Health Summary Measure Score at 26 Weeks Post-op
The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed MCS Maximum: 76.09; Minimum: -2.47.
Measured: at 26 weeks post-op
International Knee Document Committee (IKDC) at Pre-op (Baseline)
The IKDC percentage score is a subjective patients reported outcome measure (PROM) that scores a participants over all score. The PROM looks at 3 categories: symptoms, sports activity, and knee function. Scores range from 0 to 100, the final score given is interpreted as a measure of function with higher scores representing higher levels of function.
Measured: at pre-op (baseline)
International Knee Documentation Committee (IKDC) up to 26 wk Post-op
The IKDC percentage score is a subjective patients reported outcome measure (PROM) that scores a participants over all score. The PROM looks at 3 categories: symptoms, sports activity, and knee function. Scores range from 0 to 100, the final score given is interpreted as a measure of function with higher scores representing higher levels of function.
Measured: up to 26 wk post-op
The Knee Injury and Osteoarthritis Outcome Score (KOOS): Patient Reported Outcome Measure: ADL at 26 Weeks Post-op
KOOS Function in daily living (ADL) (17 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: ADL at Pre-op (Baseline)
KOOS Function in daily living (ADL) (17 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Pain at 26 Weeks Post-op
KOOS Pain (9 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Pain at Pre-op (Baseline)
KOOS Pain (9 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Quality of Life at 26 Weeks Post-op
KOOS Quality of Life (QoL) (4 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Quality of Life at Pre-op (Baseline)
KOOS Quality of Life (QoL) (4 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Sport and Recreation at 26 Weeks Post-op
KOOS Sport and Recreation (Sport/Rec) (5 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures.
Measured: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Sports and Recreation at Pre-op (Baseline)
KOOS Sport and Recreation (Sport/Rec) (5 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures.
Measured: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Symptoms at 26 Weeks Post-op
KOOS Symptoms (7 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Symptoms at Pre-op (Baseline)
KOOS Symptoms (7 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately.
Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Measured: at pre-op (baseline)
Absolute Quadriceps Volume (L) at Pre-op (Baseline)
Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at pre-op (baseline)
Absolute Quadricep Volume (L) at 26 Week Post-op
Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at 26 week post-op
Absolute Hamstring Volume (L) at Pre-op (Baseline)
Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at pre-op (baseline)
Absolute Hamstring Volume (L) at 26 Weeks Post-op
Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at 26 weeks post-op
Normalized Quadriceps Volume (L) at Pre-op (Baseline)
Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at pre-op (baseline)
Normalized Quadriceps Volume (L) at 26 Weeks Post-op
Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at 26 weeks post-op
Normalized Hamstring Volume (L) at Pre-op (Baseline)
Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at pre-op (baseline)
Normalized Hamstring Volume (L) at 26 Weeks Post-op
Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Measured: at 26 weeks post-op
Insulin Like Growth Factor (IGF1) at -1 and 5 Weeks Post-op
IGF1 was measured from serum using an IMMULITE 2000 system (Siemens).
Measured: Area under the curve between -1 and 5 weeks post-op
Myostatin at -1 and 5 Weeks Post-op
Myostatin was measured from plasma using ELISAs (R\&D Systems, Minneapolis, MN) following manufacturer recommendations.
Measured: Area under the curve between -1 and 5 weeks post-op
MMP3 at -1 and 5 Weeks Post-op
Matrix metalloproteinase-3 (MMP3) was measured from serum using ELISAs (R\&D Systems, Minneapolis, MN) following manufacturer recommendations.
Measured: Area under the curve between -1 and 5 weeks post-op
Hyaluronic Acid at -1 and 5 Weeks Post-op
Hyaluronic acid was measured from plasma using ELISAs (R\&D Systems, Minneapolis, MN) following manufacturer recommendations.
Measured: Area under the curve between -1 and 5 weeks post-op
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2015 (estimated)
- Study startMay 2015
- Primary completionOct 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Rupture of Anterior Cruciate LigamentStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital for Special Surgery, New York
- Responsible party
- Principal investigator, Christopher Mendias, PhD, ATC, University of Michigan
- Investigators
- Christopher L Mendias, PhD, ATC, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02420353
- Sponsor's protocol ID
- HUM00087702
- Other IDs
- IND Exemption 123189
- Status last verified
- Dec 2019
- First submitted
- 9 Apr 2015
- Last updated
- 6 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24081158Surya 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.
PubMed 19470622Mendias 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.
PubMed 23739685Gelato 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.
PubMed 18158071Mendias 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.
PubMed 32452208
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Recombinant Growth Hormone Therapy to Prevent Muscle Atrophy in Patients With Anterior Cruciate Ligament Tears
- ClinicalTrials.gov ID
- NCT02420353
- Acronym / sponsor ID
- HUM00087702
- Conditions
- Rupture of Anterior Cruciate Ligament
- Keywords
- muscle atrophy, growth hormone, ACL tear
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Hospital for Special Surgery, New York
- Study start
- May 2015 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 17 Apr 2015 (estimated)
- Results
- Posted 6 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Somatropin | Active comparator | Drug: SomatropinSomatropin of rDNA origin |
| Placebo | Placebo comparator | Drug: PlaceboA placebo vehicle that contains somatropin diluent but no active hormone. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SomatropinGH 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. | Drug | Somatropin |
| PlaceboA 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. | Drug | Placebo |
Primary outcome
Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op
Time frame: at 26 wks 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.
43 secondary outcomes
Normative Isokinetic Extension (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Normative Isokinetic Flexion (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Normative Isokinetic Flexion (Nm) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Normative Isometric Extension (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Normative Isometric Extension (Nm) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Normative Isometric Flexion (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Normative Isometric Flexion (Nm) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Absolute Isokinetic Extension (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Absolute Isokinetic Extension (Nm) at 26 wk Post-op
Time frame: at 26 wk post-op
Absolute Isokinetic Flexion (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Absolute Isokinetic Flexion (Nm) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Absolute Isometric Extension (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Absolute Isometric Extension (Nm) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Absolute Isometric Flexion (Nm) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Absolute Isometric Flexion (Nm) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
VR12 Health Survey: Physical Health Summary Measure Score at Pre-op (Baseline)
Time frame: at pre-op (baseline)
VR12 Health Survey: Physical Health Summary Measure Score at 26 Weeks Post-op
Time frame: at 26 weeks post-op
VR12 Health Survey: Mental Health Summary Measure Score at Pre-op (Baseline)
Time frame: at pre-op (baseline)
VR12 Health Survey: Mental Health Summary Measure Score at 26 Weeks Post-op
Time frame: at 26 weeks post-op
International Knee Document Committee (IKDC) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
International Knee Documentation Committee (IKDC) up to 26 wk Post-op
Time frame: up to 26 wk post-op
The Knee Injury and Osteoarthritis Outcome Score (KOOS): Patient Reported Outcome Measure: ADL at 26 Weeks Post-op
Time frame: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: ADL at Pre-op (Baseline)
Time frame: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Pain at 26 Weeks Post-op
Time frame: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Pain at Pre-op (Baseline)
Time frame: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Quality of Life at 26 Weeks Post-op
Time frame: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Quality of Life at Pre-op (Baseline)
Time frame: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Sport and Recreation at 26 Weeks Post-op
Time frame: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Sports and Recreation at Pre-op (Baseline)
Time frame: at pre-op (baseline)
KOOS Patient Reported Outcome Measure: Symptoms at 26 Weeks Post-op
Time frame: at 26 weeks post-op
KOOS Patient Reported Outcome Measure: Symptoms at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Absolute Quadriceps Volume (L) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Absolute Quadricep Volume (L) at 26 Week Post-op
Time frame: at 26 week post-op
Absolute Hamstring Volume (L) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Absolute Hamstring Volume (L) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Normalized Quadriceps Volume (L) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Normalized Quadriceps Volume (L) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Normalized Hamstring Volume (L) at Pre-op (Baseline)
Time frame: at pre-op (baseline)
Normalized Hamstring Volume (L) at 26 Weeks Post-op
Time frame: at 26 weeks post-op
Insulin Like Growth Factor (IGF1) at -1 and 5 Weeks Post-op
Time frame: Area under the curve between -1 and 5 weeks post-op
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24081158Boesen 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.
- Background: PubMed 19470622Surya 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.
- Background: PubMed 23739685Mendias 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.
- Background: PubMed 18158071Gelato 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.
- Derived from this study: PubMed 32452208Mendias 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher L Mendias, PhD, ATC principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Somatropin in people with Rupture of Anterior Cruciate Ligament, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op (time frame: at 26 wks post-op). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02420353, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2020.