CORR® ORS Richard A. Brand Award: Clinical Trials of a New Treatment Method for Adhesive Capsulitis

Abstract

Background Conservative and even surgical management of adhesive capsulitis often is prolonged and painful. Management of adhesive capsulitis is lacking evidencebased controlled clinical trials. Questions/Purposes We asked: (1) Does a collagenase clostridium histolyticum (CCH) injection lyse shoulder capsule collagen in adhesive capsulitis and at what dose? (2) Can a shoulder capsule injection be administered extraarticularly? (3) Do CCH injections result in better scores for pain and function than can be achieved with physical therapy among patients with adhesive capsulitis?Methods First, 60 patients with adhesive capsulitis were evaluated by clinical examination. To make the diagnosis of adhesive capsulitis, a patient had to have restricted active ROM of at least 60°in total active ROM in the affected shoulder compared with the unaffected contralateral shoulder; with the scapula stabilized, external rotation with the elbow at the side was a very important determinant. Patients were randomized to receive a single injection of 0.5 mL placebo or 0.145, 0.29, or 0.58 mg CCH. All 60 patients were followed up at 30 days. After that, if patients did not attain treatment thresholds they were eligible for up to five open-label 0.58-mg collagenase injections. For the longer-term followup in the open-label phase, 53 patients (83%) were followed to 12 months, 46 (77%) for 24 months, 36 (60%) for 36 months, 37 (62%) for 48 months, and 25 (42%) for 60 months. The extraarticular injection was directed at the anterior shoulder capsule with the patient in the supine position. To prove that these injections could be delivered reliably to the anterior shoulder capsule extraarticularly, the next study involved volunteers without adhesive capsulitis, in which 10 volunteers received a 10-mL injection of normal saline under ultrasound guidance. Finally, to determine the efficacy and dosing of CCH, four cohorts of 10 patients received up to three ultrasoundguided injections separated by 21 days. These injections were administered at one of four dose-volume levels. A fifth cohort of 10 patients was used as a control group and performed standardized home shoulder exercises only. All patients performed standardized home shoulder exercises three times daily. For Study 3, followup was at 22, 43, 64, and 92 days. No patients were lost to followup. Results In the first study, a single CCH injection did not provide clinically important improvements from baseline in active ROM, passive ROM, and function and pain scores compared with patients who received placebo. UltrasoundThe Stony Brook University Research Foundation and MAB and EDW received funding from Auxilium Pharmaceutical, Inc.

Accuracy of unguided and ultrasound guided Coracohumeral ligament infiltrations – a feasibility cadaveric case series

“…Infiltrations delivered between the glenohumeral joint capsule and the CHL would lie in the rotator interval, a structure implicated in GHIAC. These infiltrations would be considered clinically effective, especially in the light of recent work on collagenase infiltrations with positive outcome attributed to the effect on the rotator interval and the CHL [25].…”

“…The upper, middle and lower trunks of the brachial plexus, cephalic vein, axillary artery and vein are all located medially and inferiorly to the coracoid process [29,30] and therefore remote from the infiltration. A similar infiltration approach has been utilized to target the glenohumeral anterior capsule with collagenase infiltration without serious complications [25]. As intraarticular corticosteroid infiltration is advocated in the treatment of GHIAC and may be chondroprotective [31][32][33], this risk is not incurred.…”

Outcomes From Conservative Treatment of Shoulder Idiopathic Adhesive Capsulitis and Factors Associated With Developing Contralateral Disease

“…A diagnosis of idiopathic adhesive capsulitis was made by physical examination demonstrating a deficit of at least 60° in total active range of motion in the affected shoulder or a deficit of at least 30° in active range of motion in 1 or more of the movements including forward flexion, abduction, external rotation, or internal rotation at 90° of shoulder abduction compared with the contralateral unaffected shoulder. 4 Total active range of motion was defined as the sum of active forward flexion, abduction, external rotation, and internal rotation at 90° of shoulder abduction. 4 For patients presenting with bilateral idiopathic adhesive capsulitis, range of motion was compared with age- and sex-matched normal motion in asymptomatic patients.…”

“… 4 Total active range of motion was defined as the sum of active forward flexion, abduction, external rotation, and internal rotation at 90° of shoulder abduction. 4 For patients presenting with bilateral idiopathic adhesive capsulitis, range of motion was compared with age- and sex-matched normal motion in asymptomatic patients. 6 …”

Shoulder Stiffness – How to Treat?

“…Extra-articular injections of Clostridium histolyticum collagenase were evaluated as a further treatment option for shoulder stiffness. However, therapeutic use, which was studied in an RCT with a small number of cases, requires further tests of safety and efficacy before a conclusion can be drawn about use in routine clinical practice [42].…”