ZILRETTA™ for Treatment of Idiopathic Adhesive Capsulitis

Study Overview
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Brief Summary
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Adhesive capsulitis is a fairly common orthopedic condition that causes pain and loss of range of motion. There are a variety of ways to treat adhesive capsulitis, one of them being an intra-articular steroid injection. This is done to help decrease the inflammatory response caused by adhesive capsulitis. In this study, all participants will receive an intra-articular glenohumeral injection of ZILRETTA and will be followed up with at four time points over 1 year to observe pain, function and range of motion following the injection.

Detailed Description
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Adhesive capsulitis is a painful shoulder condition characterized by a gradual loss of both passive and active range of motion due to inflammatory changes and eventual fibrosis and contracture of the shoulder joint capsule. It occurs in about 2% to 5% of the population, and a majority of patients are female. The true cause of the condition remains unclear, however, it has been proposed that the initial synovitis stimulates the development of a fibrotic cascade. The development of adhesive capsulitis has been associated with diabetes mellitus, thyroid dysfunction, Dupuytrens contractures, autoimmune diseases and treatments for certain cancers. Adhesive capsulitis progresses through four predictable phases, defined by symptoms, physical examination, arthroscopic appearance and biopsies. Regardless of stage, the mainstay of treatment for adhesive capsulitis of the shoulder is conservative, focused mainly on physical therapy combined with a home exercise program, regardless of stage. Pharmacologic agents are often used as adjuncts to physical therapy, and include nonsteroidal anti-inflammatory medications (NSAIDs), oral corticosteroids and intra-articular injections of corticosteroids. Although a large percentage of patients in the early stages of disease respond well to conservative treatments, those who fail therapy and injections may require surgical intervention, including arthroscopy with lysis of adhesions and/or manipulation under anesthesia. Numerous studies have investigated the effect and success of injections combined with standard physical therapy for adhesive capsulitis of the shoulder. In general, intra-articular injection of corticosteroids has been found to be superior to administration of oral cortisone and at least equivalent to manipulation under anesthesia alone. Injections have been shown to reduce pain quicker and result in earlier return of range of motion. Low doses of steroid appear equally as effective as higher doses. Image-guided injections, whether ultrasound or fluoroscopic guided injections, have also been shown to be more effective than blinded injections. Failure of an injection and therapy to provide relief either results in a repeat image-guided injection or surgical intervention, both of which have significant associated cost and potential morbidity. Thus, there would be significant potential value to a long-acting, sustained release intra-articular steroid injection for the treatment of adhesive capsulitis of the shoulder. Zilretta®, triamcinolone acetonide extended release suspension 32 mg, is a microsphere formulation of injectable steroid which is FDA-approved for and has shown significant promise for the treatment of knee osteoarthritis. This long-acting steroid could have several important advantages in the treatment of shoulder adhesive capsulitis. It may potentiate and prolong the anti-inflammatory effect of the steroid, and potentially avoid the need for costly additional image-guided injections or expensive and potentially morbid surgery. An additional potential benefit is less elevation of peripheral blood glucose in diabetics, a known complication of traditional steroid injections that has been demonstrated to be mitigated using a sustained release formulation. Out primary aim in this study is to assess patient reported pain and outcomes in patients with idiopathic adhesive capsulitis of the shoulder at 3, 6 and 12 months following single, image guided ZILRETTA injection.

Official Title
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A Stratified Investigation of a Single Injection of ZILRETTA™ (Triamcinolone Acetonide Extended-release Injectable Suspension) for Symptomatic Relief in Patients With Idiopathic Adhesive Capsulitis of the Shoulder

Conditions
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Adhesive Capsulitis, Frozen Shoulder, Adhesive Capsulitis of Shoulder

Intervention / Treatment
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* Drug: triamcinolone acetonide extended-release injectable suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic adhesive capsulitis (onset <6 months prior) Pain rating of 5 or greater out of 10 on 0-10 scale at time of enrollment Willing to come on site for follow up evaluations at 1 month, 3 months, 6 months, and 12 months after the injection Exclusion Criteria: Active workers compensation case Known psychiatric disorders under active treatment Uncontrolled diabetes (defined as diabetic ketoacidosis, severe peripheral neuropathy, ophthalmologic or renal manifestations) Diagnosed osteoarthritis of the ipsilateral or contralateral shoulder Painful joint condition in another part of the body affecting perceived pain

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects receive the ZILRETTA injection
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZILRETTA<br>Single injection of triamcinolone acetonide extended-release injectable suspension, injected in the glenohumeral joint under ultrasound guidance. | Drug: triamcinolone acetonide extended-release injectable suspension<br>* ZILRETTA (triamcinolone acetonide extended-release injectable suspension) injection in the glenohumeral joint administered under ultrasound guidance.<br>* Other names: ZILRETTA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale Score | Pain rating on a scale of 0-10, higher numbers indicating a worse outcome | 6 months after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American Shoulder and Elbow Society Score | Pain and function patient reported outcome for the shoulder. Scores range from 0 to 100 with a score of 0 indicating a worse shoulder condition and 100 indicating a better shoulder condition. | 6 months after injection | 
| American Shoulder and Elbow Society Score | Pain and function patient reported outcome for the shoulder. Scores range from 0 to 100 with a score of 0 indicating a worse shoulder condition and 100 indicating a better shoulder condition. | 12 months after injection | 
| PROMIS Physical Function Score | Patient reported outcome measuring physical function level measured by T scores and standard deviations. The average is 50, so a T score lower than 50 indicates a worse outcome. | 6 months after injection | 
| PROMIS Physical Function Score | Patient reported outcome measuring physical function level measured by T scores and standard deviations. The average is 50, so a T score lower than 50 indicates a worse outcome. | 12 months after injection | 
| Triplanar Range of Motion | Shoulder range of motion | 1 month after injection | 
| Triplanar Range of Motion | Shoulder range of motion | 3 months after injection | 
| Triplanar Range of Motion | Shoulder range of motion | 6 months after injection | 
| Triplanar Range of Motion | Shoulder range of motion | 12 months after injection | 
| Need for another injection | Yes or no answer if the patient needed another corticosteroid injection during their time enrolled in the study | 12 months after injection | 
| Time to second injection (if applicable) | how long after the ZILRETTA injection the patient needed another corticosteroid injection | 12 months after injection |