ZILRETTA™ for Treatment of Idiopathic Adhesive Capsulitis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Adhesive Capsulitis of Shoulder; Adhesive Capsulitis; Frozen Shoulder
• Intervention / Treatment: Drug: triamcinolone acetonide extended-release injectable suspension

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kaitlyn Shank, MEd, ATC; Phone Number: 434-243-5653; Email: kshank@virginia.edu
• Study Contact Backup: Name: Lizzie Leitch, MEd, ATC; Phone Number: 434-243-0256; Email: ebl7nu@hscmail.mcc.virginia.edu

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
      • Contact: Kaitlyn Shank, MEd, ATC; Phone Number: 434-243-5653; Email: kshank@virginia.edu
      • Contact: Lizzie Leitch, MEd, ATC; Phone Number: 434-243-0256; Email: ebl7nu@hscmail.mcc.virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Brian Werner, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2019
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Bursitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: 21584

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes