Lipoic Acid for Neuroprotection in Secondary Progressive Multiple Sclerosis (P1.373)

Abstract

OBJECTIVE: To determine if Lipoic acid (LA) is neuroprotective, reduces disability, improves quality of life, and is safe in a secondary progressive multiple sclerosis (SPMS) population. BACKGROUND: LA is an inexpensive and readily-available oral antioxidant supplement. LA decreases inflammation and reduces optic nerve and spinal cord atrophy in experimental autoimmune encephalitis (EAE). LA reaches therapeutic blood levels and is tolerated at high doses in people with MS. LA may exert its effects by reducing microglial activation. DESIGN/METHODS: We conducted a 2 year, double-blind, randomized controlled trial of 1200mg daily LA versus placebo. The last subject exited August, 2015. Primary outcome was reduction in MRI whole brain atrophy. Secondary outcomes included atrophy of brain substructures, spinal cord atrophy, retinal and macular atrophy, changes in neurological exam, walking, cognition, fatigue, and quality of life. Pharmacokinetic labs were drawn at baseline and month 12. Adverse events and safety laboratory measures were monitored. RESULTS: Of the 54 randomized subjects, 51 subjects took at least 1 dose of study drug and were included in analysis. Average age was 58.5±5.9 (40-69) years, 61[percnt] were female, and 96[percnt] Caucasian. Average disease duration was 29.6±9.5 (9-51) years and median EDSS 6.0 (3.0-9.0). Four (7.8[percnt]) subjects terminated early (1 each of glomerulonephritis, testicular cancer, renal failure, MRI intolerance). Common adverse event categories were injuries (40), infections (40), and gastrointestinal disorders (21). Compliance, measured by pill counts, was > 90[percnt] in 93[percnt] of subjects and >80[percnt] for all subjects. Mean baseline CMax was 3.04±0.43 (0.69-8.47) ng/ml with no significant difference at month 12. CONCLUSIONS: LA demonstrated safety, tolerability, and high compliance over 2 years. LA achieved therapeutic blood levels at values comparable with those previously reported. Primary and secondary outcomes will be presented on the effectiveness of this inexpensive antioxidant. Study supported by: Department of Veterans Affairs, RR&D Service.

Disclosure: Dr. Spain has nothing to disclose. Dr. Murchison has received research support from NINDS. Dr. Horak has received personal compensation for activities with Consensus Medical and North American Education, and APDM. Dr. Simon has received research support for activities with Biogen Idec. Dr. Bourdette has received personal compensation for activities with Biogen Idec, Serono, and Teva Neurosciences as a speaker/faculty.