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

Study Overview
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Brief Summary
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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.

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

Conditions
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Tendinopathy

Intervention / Treatment
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* Drug: Somatropin
* Drug: Bacteriostatic saline
* Other: Progressive exercise program
* Procedure: Patellar tendon biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Drug: Somatropin<br>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<br>* Active drug<br>* Other names: Human growth hormone;Other: Progressive exercise program<br>* 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.<br>Procedure: Patellar tendon biopsy<br>* 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.<br>|
| Placebo Comparator: Drug: Placebo<br>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. | Drug: Bacteriostatic saline<br>* Placebo, the diluent used to reconstitute somatropin<br>* Other names: 0.9% NaCl;Other: Progressive exercise program<br>* 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.<br>Procedure: Patellar tendon biopsy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patellar tendinopathy, somatropin, jumper's knee