Journal of Clinical Neurology and Neurosurgery

Safety and Efficacy of Novel Epidural Clonidine Micropellets for Lumbosacral Radiculopathy

Abstract

Nagy A Mekhail*, Ali R Rezai, Pragya B Gupta, W Porter McRoberts, Gregory J Fiore, Bryan A Jones, Lou-Anne G Acevedo-Moreno, Chris J Gilligan and Ramsin M Benyamin

Background: Chronic back and leg pain is a leading cause of disability and results in a significant health care expenditure. Options such as physical therapy, corticosteroids Epidural Injections (ESI) or spine surgery have limited long term benefit and may cause significant morbidity. Clonidine has anti-neuropathic pain and anti-inflammatory properties. A novel, slow-release biodegradable polymer (Poly (D, L-lactide) clonidine micropellets deliver sustained, high clonidine levels and may provide prolonged pain relief with minimal systemic side effects. Methods: A pilot multicenter investigation of the safety, pharmacokinetics (PK) and effectiveness of clonidine micropellets in patients with chronic lumbosacral radiculopathy. Three sequential cohorts of 18 subjects each received a single epidural injection of clonidine 0.325 mg, 0.975 mg or 1.95 mg (1, 3 or 6 micropellets, respectively) at the interlaminar epidural level that corresponds to the painful dermatomes. Clonidine PK was evaluated at multiple time points for 84 days. Paired t-tests were performed to examine changes from baseline within each cohort, and analysis of covariance evaluated differences between dose levels. NRS and RMS-Q disability scores were recorded at baseline and for one year follow up. Results: Peak plasma clonidine was observed 24h after injection and the mean elimination half-life ranged from 13 to 20 days. Statistically significant reduction in leg and back pain from baseline at all-time points up to 1 year was observed, in all cohorts as well as significant improvement in the RMS-Q at all timepoints. Adverse events and rescue medications were also recorded. Conclusion: Clonidine Micropellets would safely and slowly deliver clonidine over a prolonged period. Clonidine’s anti-neuropathic and anti-inflammatory effects could treat the radicular back and leg pain.