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

Background Conservative and even surgical management of adhesive capsulitis often is prolonged and painful. Management of adhesive capsulitis is lacking evidence-based 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 ultrasound-guided 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, pass