A Study to Evaluate the Efficacy of Somatropin in the Treatment of Patellar Tendinopathy

A Double-Blind Placebo-Controlled Study to Evaluate the Efficacy of Somatropin in the Treatment of Patellar Tendinopathy

Patellar tendinopathy is one of the most frequent causes of non-traumatic knee pain and reduced function in patients. Standard treatment options for patellar tendinopathies include non-steroidal anti-inflammatory drugs, corticosteroids, cryotherapy, manual therapy, eccentric exercises, and ultrasound. Unfortunately many patients fail to respond to these therapies and return to normal activity levels, and recurrence rates for those who do respond are unacceptably high. Many patients who fail to respond display persistent degenerative changes on imaging studies suggesting a failure to regenerate the pathological tissue. Developing new therapies that can directly promote the synthesis of new, healthy extracellular matrix tissue could therefore address an important therapeutic need and make a substantial improvement in our ability to effectively treat patellar tendinopathy and reduce recurrence rates. Somatropin (human growth hormone of recombinant DNA origin) has been shown to increase protein synthesis and matrix production when delivered directly into the tendon. This study will evaluate the ability of somatropin to improve clinical outcomes and tissue quality in patients with chronic tendinopathy.

Study Overview

• Status: Withdrawn
• Conditions: Tendinopathy
• Intervention / Treatment: Drug: Somatropin; Other: Progressive exercise program; Procedure: Patellar tendon biopsy; Drug: Bacteriostatic saline

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females ages 18 - 50
• Patients with a greater than 3 month history of anterior knee pain
• Patients with a confirmed diagnosis of patellar tendinopathy (confirmation by ultrasonography demonstrating local anterior-posterior thickening of the tendon of at least 1mm compared with the mid-tendon level, and a hypo-echoic area)

Exclusion Criteria:

• Patients who have received corticosteroid injections within 12 months
• Patients who have full-width disruptions of the patellar tendon
• Patients who have undergone previous knee surgery or intraarticular injury
• Patients who have have arthritis (Kellgren and Lawrence grade 2 or higher), open growth plates, diabetes, cardiovascular disease, history of cancer or any major medical illnesses or endocrine disorders
• Patients with a body mass index greater than 35
• Women who are pregnant or planning to become pregnant
• Patients who are current collegiate, professional or elite athletes, or are participating in sports organizations that currently ban the use of somatropin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Drug: Somatropin; Under ultrasound guidance, patients will receive an injection of somatropin (0.1mg in a volume of 0.2mL of bacteriostatic saline) into the area of tendinopathic lesion. A series of three injections will be delivered one week apart. Vials will be blinded.	Drug: Somatropin; Active drug; Other Names: Growth hormone; Human growth hormone; Other: Progressive exercise program; Over a 12 week period beginning at the second study visit patients will perform a standard of care eccentric exercise training regime. Each session consists of three bilateral exercises: leg press, back squat, and hack squat. Subjects will complete four sets in each exercise with a 2-3 minute rest between sets. The repetitions/loads are: 15 repetition maximum (RM) week 1, 12RM weeks 2-3, 10RM weeks 4-5, 8RM weeks 6-8 and 6RM weeks 9-12. All exercises are performed from complete 0º to 90º of knee flexion and back again. Each of the eccentric and concentric phases will occur over a period of 3 seconds, respectively for a total of 6 seconds per contraction.; Procedure: Patellar tendon biopsy; Bilateral biopsies will be performed on an elective basis, although the investigators will aim to have 8 subjects in each group receive the biopsy. Biopsies will be obtained at the 26 week time point. The data obtained from the biopsy will help address the mechanism behind observed changes in outcome scores, physical measurements or imaging studies. The biopsy will be performed under ultrasound guidance and using sterile technique with a disposable 14G, 2cm biopsy instrument.
Placebo Comparator: Drug: Placebo; Under ultrasound guidance, patients will receive an injection of 0.2mL of bacteriostatic saline (which is an equivalent volume of diluent used in the active comparator arm) into the area of tendinopathic lesion. A series of three injections will be delivered one week apart. Vials will be blinded.	Other: Progressive exercise program; Over a 12 week period beginning at the second study visit patients will perform a standard of care eccentric exercise training regime. Each session consists of three bilateral exercises: leg press, back squat, and hack squat. Subjects will complete four sets in each exercise with a 2-3 minute rest between sets. The repetitions/loads are: 15 repetition maximum (RM) week 1, 12RM weeks 2-3, 10RM weeks 4-5, 8RM weeks 6-8 and 6RM weeks 9-12. All exercises are performed from complete 0º to 90º of knee flexion and back again. Each of the eccentric and concentric phases will occur over a period of 3 seconds, respectively for a total of 6 seconds per contraction.; Procedure: Patellar tendon biopsy; Bilateral biopsies will be performed on an elective basis, although the investigators will aim to have 8 subjects in each group receive the biopsy. Biopsies will be obtained at the 26 week time point. The data obtained from the biopsy will help address the mechanism behind observed changes in outcome scores, physical measurements or imaging studies. The biopsy will be performed under ultrasound guidance and using sterile technique with a disposable 14G, 2cm biopsy instrument.; Drug: Bacteriostatic saline; Placebo, the diluent used to reconstitute somatropin; Other Names: Saline; 0.9% NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Victorian Institute of Sport Assessment Patellar outcome score from enrollment	Week 1 to week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patient completed visual analog scale (VAS) of knee pain levels		Week 1, 2, 3, 4, 9, 14, 26
Change in patient completed Victorian Institute of Sport Assessment Patellar outcome score		Week 1, 2, 3, 4, 9, 14, 26
Change in patient completed Patient Reported Outcomes Measurement Instrument System (PROMIS) Physical Function Computer Adaptive Test		Week 1, 2, 3, 4, 9, 14, 26
Change in patient completed Patient Reported Outcomes Measurement Instrument System (PROMIS) Short Form Global Health Scale		Week 1, 2, 3, 4, 9, 14, 26
Ultrasound assessment of patellar tendon quality	Five point assessment scale of tendon quality (0 Normal, Normal tendon structure; 1 Mild, Ill-defined abnormal hypoechogenicity; 2 Moderate, Well-defined abnormal hypoechogenicity; 3 Severe, Well-defined abnormal hypoechogenicity and anechoic clefts; 4 Complete, Full-width tendon disruption or tear)	Weeks 1, 14, 26
Electron micrographs of patellar tendon biopsy sample	Bilateral biopsies will be taken, and the size (measured in squared nanometers) will be measured	Week 26
Gene expression of patellar tendon biopsy sample	Bilateral biopsies will be taken, and the expression of genes will be measured with microarrays or RNA-sequencing	Week 26

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Investigators: Principal Investigator: Christopher L Mendias, PhD, ATC, Hospital for Special Surgery, New York

Publications and helpful links

General Publications

• Kongsgaard M, Kovanen V, Aagaard P, Doessing S, Hansen P, Laursen AH, Kaldau NC, Kjaer M, Magnusson SP. Corticosteroid injections, eccentric decline squat training and heavy slow resistance training in patellar tendinopathy. Scand J Med Sci Sports. 2009 Dec;19(6):790-802. doi: 10.1111/j.1600-0838.2009.00949.x. Epub 2009 May 28.
• 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.
• Boesen AP, Dideriksen K, Couppe C, Magnusson SP, Schjerling P, Boesen M, Aagaard P, Kjaer M, Langberg H. Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation. J Appl Physiol (1985). 2014 Jan 15;116(2):192-203. doi: 10.1152/japplphysiol.01077.2013. Epub 2013 Nov 14.
• Gumucio JP, Sugg KB, Mendias CL. TGF-beta superfamily signaling in muscle and tendon adaptation to resistance exercise. Exerc Sport Sci Rev. 2015 Apr;43(2):93-9. doi: 10.1249/JES.0000000000000041.
• Heinemeier KM, Mackey AL, Doessing S, Hansen M, Bayer ML, Nielsen RH, Herchenhan A, Malmgaard-Clausen NM, Kjaer M. GH/IGF-I axis and matrix adaptation of the musculotendinous tissue to exercise in humans. Scand J Med Sci Sports. 2012 Aug;22(4):e1-7. doi: 10.1111/j.1600-0838.2012.01459.x. Epub 2012 Mar 19.
• Visentini PJ, Khan KM, Cook JL, Kiss ZS, Harcourt PR, Wark JD. The VISA score: an index of severity of symptoms in patients with jumper's knee (patellar tendinosis). Victorian Institute of Sport Tendon Study Group. J Sci Med Sport. 1998 Jan;1(1):22-8. doi: 10.1016/s1440-2440(98)80005-4.
• Hung M, Stuart AR, Higgins TF, Saltzman CL, Kubiak EN. Computerized Adaptive Testing Using the PROMIS Physical Function Item Bank Reduces Test Burden With Less Ceiling Effects Compared With the Short Musculoskeletal Function Assessment in Orthopaedic Trauma Patients. J Orthop Trauma. 2014 Aug;28(8):439-43. doi: 10.1097/BOT.0000000000000059.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 4, 2015
• First Posted (Estimate): November 5, 2015

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: somatropin; patellar tendinopathy; jumper's knee
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Tendinopathy; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: HUM00107019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No