Safety and Effectiveness of Placental Connective Tissue Matrix Allograft Versus Corticosteroid Injection in Adhesive Capsulitis: A Double-Blinded Prospective Randomized Study.

Background: Adhesive capsulitis causes significant pain and functional limitation, with limited effective treatment options. Current standard-of-care treatments, such as corticosteroid injections, may offer short-term symptom relief but are associated with limited long-term efficacy and potential side effects. Regenerative therapies using extracellular matrix-based products derived from placental tissue have shown promise in treating musculoskeletal injuries due to their anti-inflammatory and tissue-healing properties. Clinical data supporting their use in adhesive capsulitis remains limited. The objective of this study was to compare the safety and effectiveness of a flowable placental connective tissue matrix allograft (PCTMA) vs. corticosteroid injection for adhesive capsulitis. Hypothesis: We hypothesized that intra-articular injection of a placental connective tissue allograft would result in superior clinical outcomes compared with corticosteroid injection for adhesive capsulitis of the shoulder. Study Design: Randomized controlled clinical trial. Methods: This double-blinded prospective study randomized patients with adhesive capsulitis to receive either intra-articular PCTMA (1 cc) with lidocaine (study group, n = 25) or corticosteroid injection with triamcinolone 20 mg and lidocaine (control group, n = 27). Inclusion criteria included ages 18 to 75 years, clinical diagnosis of adhesive capsulitis, shoulder pain >6 weeks, and MRI confirmation without other shoulder pathology. The primary end point was change from baseline in Shoulder Pain and Disability Index (SPADI) score. Secondary end points included Visual Analog Scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, and passive range of motion. Assessments occurred at 4, 12, and 24 weeks postinjection. Results: Both groups improved over time. At 24 weeks, mean SPADI improvement was similar between groups [PCTMA: -40.4 (SD 18.81) vs. corticosteroid: -37.7 (SD 30.12)] (p = 0.73), but post hoc responder analyses favored PCTMA: SPADI responders 88% vs. 63% (p = 0.04), VAS responders 80% vs. 56% (p = 0.06), and ASES responders 88% vs. 56% (p = 0.01). One serious adverse event unrelated to the study intervention was reported. Conclusion: Flowable intra-articular PCTMA demonstrated a favorable safety profile and comparable improvements in pain and disability to corticosteroid injection at 24 weeks. A post hoc responder analysis favored PCTMA, suggesting potential for more sustained clinical benefit warranting further investigation. Clinical Relevance: This study provides the first randomized controlled comparison of PCTMA vs. corticosteroid injection for adhesive capsulitis, offering preliminary evidence to guide treatment selection and informing the design of future, larger-scale trials investigating biologic therapies for this condition. Trial Registration: The authors confirm that the protocol was finalized before patient enrollment. Clinical trial registration (NCT05844930) was completed in April 2023. Level of Evidence: Therapeutic Level II.See Instructions for Authors for a complete description of levels of evidence.