Efficacy of conditioned autologous serum therapy (Orthokine®) on the dorsal root ganglion in patients with chronic radiculalgia: study protocol for a prospective randomized placebo-controlled double-blind clinical trial (RADISAC trial).

Background: Pulsed radiofrequency (PRF) treatment on the dorsal root ganglion (DRG) has been proposed as a good option for the treatment of persistent radicular pain based on its effect of neuromodulation on neuropathic pain. Autologous conditioned serum (ACS) therapy is a conservative treatment based on the patient's own blood. The aim of this manuscript is to develop a study protocol using ACS on the DRG as a target for its molecular modulation.

Methods: We plan to conduct a randomized controlled study to compare the efficacy of PRF therapy plus ACS versus PRF therapy plus physiological saline 0.9% (PhS) on the DRG to reduce neuropathic pain in patients with persistent lower limb radiculalgia (LLR) and to contribute to the functional improvement and quality of life of these patients. Study participants will include patients who meet study the inclusion/exclusion criteria. Eligible patients will be randomized in a 1:1 ratio to one of treatment with PRF plus ACS (experimental group) or PRF plus PhS (placebo group). The study group will consist of 70 patients (35 per group) who have experienced radicular pain symptoms for ≥ 6 months' duration who have failed to respond to any therapy. Both groups will receive PRF on the DRG treatment before the injection of the sample (control or placebo). Patient assessments will occur at baseline, 1 month, 3 months, 6 months, and 12 months after therapy. The primary efficacy outcome measure is Numeric Pain Rating Scale (NPRS) responders from baseline to 12 months of follow-up using validated minimal important change (MIC) thresholds. A reduction of ≥ 2 points in NPRS is considered a clinically significant pain relief. The secondary efficacy outcome measure is the proportion of Oswestry Low Back Pain Disability Scale (ODS) responders from baseline to 12 months of follow-up in the experimental group (PRF plus ACS) versus the placebo group (PRF plus PhS). ODS responders are defined as those patients achieving the validated MIC of ≥ 10-point improvement in ODS from baseline to 12 months of follow-up as a clinically significant efficacy threshold.

Discussion: This prospective, double-blind, randomized placebo-controlled study will provide level I evidence of the safety and effectiveness of ACS on neuropathic symptoms in LLR patients. TRIAL REGISTRATION {2A}{2B}: EUDRACT number: 2021-005124-38. Validation date: 13 November 2021. Protocol version {3}: This manuscript presents the 2nd protocol version.