Combined Acupuncture and Moxibustion for Chronic Nonspecific Low Back Pain: A Three-Arm Assessor-Blinded Randomized Trial with Inflammatory Biomarker Assessment

Abstract

Background: Chronic nonspecific low back pain (CNLBP) represents a leading global cause of disability. Long-term pharmacological management is restricted by various adverse effects, while complementary acupuncture-moxibustion is widely applied in clinical practice. High-quality three-arm randomized trials quantifying the incremental benefit of supplementary moxibustion remain scarce, and correlations between clinical gains and systemic inflammatory changes require further clinical verification. Objective: This trial aimed to evaluate incremental clinical benefits of adding moxibustion to standardized acupuncture relative to acupuncture monotherapy and conventional rehabilitation, and explore potential correlations between symptom improvement and peripheral inflammatory fluctuations. Methods: This prospective single-center assessor-blinded three-arm randomized trial was performed following CONSORT 2010 and STRICTA 2010 guidelines, prospectively registered at Chinese Clinical Trial Registry (ChiCTR240008569, registration date: March 12, 2024; recruitment initiated from March 15, 2024 to September 30, 2024; final follow-up finished March 2025). A total of 156 eligible participants were randomized at a 1:1:1 ratio. The primary endpoint was adjusted between-group difference in week-8 NRS change from baseline. Secondary endpoints included ODI, PSQI, EQ-5D-5L, PGIC, weekly paracetamol consumption and serum hs-CRP, IL-6, TNF-α. Intention-to-treat (ITT) served as primary analysis set, per-protocol (PP) for sensitivity analysis (Global Burden of Disease Collaborative Network, 2023); multiple imputation with 20 chained datasets was adopted for missing values. Linear mixed-effects model and ANCOVA corrected for baseline covariates; Bonferroni correction was applied for secondary outcome pairwise comparisons. Results: Among 192 screened patients, 36 were excluded and 156 randomized. Eleven participants dropped out within the 8-week intervention, with another six lost to follow-up from week 8 to week 24; 145 completed 8-week treatment and 139 finished the final 24-week follow-up. All baseline indicators were balanced across three groups (all P>0.05). At week 8, combined therapy yielded superior NRS reduction versus acupuncture alone (adjusted MD = −1.18, 95% CI: −1.74 to −0.62, P < 0.001, Cohen’s d=0.78) and rehabilitation (adjusted MD = −2.31, 95% CI: −2.89 to −1.73, P < 0.001, Cohen’s d=1.24), and the inter-group difference exceeded predefined MCID of 1.0 point. Significant improvements in ODI, PSQI and EQ-5D persisted up to week 24. The proportion of patients achieving ≥50% NRS reduction was 61.5%, 38.5% and 19.2% for combined, acupuncture and rehabilitation groups respectively; weekly paracetamol intake decreased by 74.2%, 50.0% and 25.0% (Qaseem A, et al., 2017). Serum pro-inflammatory cytokines declined more substantially in combined cohort. Only mild, self-limited adverse events occurred with no severe adverse incidents recorded. Conclusion: Combined acupuncture-moxibustion generates statistically and clinically meaningful extra benefits for CNLBP in pain relief, physical function, sleep and quality of life alongside reduced rescue analgesic intake, with durable therapeutic effects sustained for six months. Reduced peripheral inflammatory markers suggest potential associations between clinical remission and alleviated systemic low-grade inflammation, without definitive causal evidence. Further multicenter sham-controlled trials are required to validate present findings.