Impact of a Multimodal Intervention Combining Manual Therapy, Exercise, Reduced Methylxanthine Intake, and Nocturnal Light Avoidance on Inflammatory and Metabolic Profiles, Pain, Functionality, and Sleep Quality in Patients with Frozen Shoulder: A Single-Blind Randomized Controlled Trial.

Frozen shoulder (FS) is a common musculoskeletal condition with significant socioeconomic impact. Despite its prevalence, the condition lacks a definitive understanding and universally effective treatment approach. To evaluate the effects of an intervention combining manual therapy, conventional exercises, and strategies to improve sleep quality and circadian rhythm on recovery and biomarkers in patients with FS. A single-blind, randomized, controlled trial was conducted with 34 participants divided into control and experimental groups (n = 17 each). Both groups received manual therapy and conventional exercises, while the experimental group (EG) also received sleep and circadian rhythm optimization instructions. Biomarkers (fasting glucose, insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA) index, leptin, triglycerides, total cholesterol, HDL cholesterol, uric acid, CRP, IL-1β, IL-6, IL-17, IL-10, IL-33, HMGB1, and TNF-α) and functional outcomes (SPADI, ROM, and PSQI) were assessed pre- and post-intervention. After six weeks, the EG showed significant improvements in IL-10 levels (mean change: 2.5 pg/mL vs. 0.5 pg/mL in the control group (CG), = 0.03), IL-6 reduction (-1.8 pg/mL vs. -0.4 pg/mL, = 0.02), and HOMA index (-0.8 vs. -0.2, = 0.04). ROM improved by 20 degrees in the EG versus 10 degrees in the CG ( = 0.01), SPADI scores decreased by 25 points versus 15 points ( = 0.03), and PSQI improved by 4 points compared to 2 points ( = 0.05). The integration of sleep quality and circadian rhythm optimization into conventional rehabilitation significantly enhances recovery, particularly IL-10 modulation, but these did not translate into superior clinical improvements within the study period. Further long-term studies are needed to confirm whether early biological effects lead to sustained functional recovery in FS patients.