Clinical trial NCT04831255: ZILRETTA™ for Treatment of Idiopathic Adhesive Capsulitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Adhesive Capsulitis
Frozen Shoulder
Adhesive Capsulitis of Shoulder
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2021-04-05
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects receive the ZILRETTA injection
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Visual Analog Scale Score
timeFrame: 6 months after injection
Secondary outcomes:
measure: American Shoulder and Elbow Society Score
timeFrame: 6 months after injection
measure: American Shoulder and Elbow Society Score
timeFrame: 12 months after injection
measure: PROMIS Physical Function Score
timeFrame: 6 months after injection
measure: PROMIS Physical Function Score
timeFrame: 12 months after injection
measure: Triplanar Range of Motion
timeFrame: 1 month after injection
measure: Triplanar Range of Motion
timeFrame: 3 months after injection
measure: Triplanar Range of Motion
timeFrame: 6 months after injection
measure: Triplanar Range of Motion
timeFrame: 12 months after injection
measure: Need for another injection
timeFrame: 12 months after injection
measure: Time to second injection (if applicable)
timeFrame: 12 months after injection
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Brian Werner, MD
role: PRINCIPAL_INVESTIGATOR
References: