RT Journal Article
SR Electronic
T1 Lipoic acid in secondary progressive MS
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e374
DO 10.1212/NXI.0000000000000374
VO 4
IS 5
A1 Rebecca Spain
A1 Katherine Powers
A1 Charles Murchison
A1 Elizabeth Heriza
A1 Kimberly Winges
A1 Vijayshree Yadav
A1 Michelle Cameron
A1 Ed Kim
A1 Fay Horak
A1 Jack Simon
A1 Dennis Bourdette
YR 2017
UL http://nn.neurology.org/content/4/5/e374.abstract
AB Objective: To determine whether lipoic acid (LA), an endogenously produced antioxidant, slowed the whole-brain atrophy rate and was safe in secondary progressive MS (SPMS).Methods: Patients with SPMS aged 40–70 years enrolled in a single center, 2-year, double-blind, randomized trial of daily oral 1,200 mg LA vs placebo. Primary outcome was change in annualized percent change brain volume (PCBV). Secondary outcomes were changes in rates of atrophy of segmented brain, spinal cord, and retinal substructures, disability, quality of life, and safety. Intention-to-treat analysis used linear mixed models.Results: Participation occurred between May 2, 2011, and August 14, 2015. Study arms of LA (n = 27) and placebo (n = 24) were matched with mean age of 58.5 (SD 5.9) years, 61% women, mean disease duration of 29.6 (SD 9.5) years, and median Expanded Disability Status Score of 6.0 (interquartile range 1.75). After 2 years, the annualized PCBV was significantly less in the LA arm compared with placebo (−0.21 [standard error of the coefficient estimate (SEE) 0.14] vs −0.65 [SEE 0.10], 95% confidence interval [CI] 0.157–0.727, p = 0.002). Improved Timed 25-Foot Walk was almost but not significantly better in the LA than in the control group (−0.535 [SEE 0.358] vs 0.137 [SEE 0.247], 95% CI −1.37 to 0.03, p = 0.06). Significantly more gastrointestinal upset and fewer falls occurred in LA patients. Unexpected renal failure (n = 1) and glomerulonephritis (n = 1) occurred in the LA cohort. Compliance, measured by pill counts, was 87%.Conclusions: LA demonstrated a 68% reduction in annualized PCBV and suggested a clinical benefit in SPMS while maintaining favorable safety, tolerability, and compliance over 2 years.ClinicalTrials.gov identifier: NCT01188811.Classification of evidence: This study provides Class I evidence that for patients with SPMS, LA reduces the rate of brain atrophy.AE=adverse event; CI=confidence interval; EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Status Scale; GI=gastrointestinal; ITT=intention to treat; LA=lipoic acid; MP-RAGE=magnetization-prepared rapid acquisition gradient echo; OCT=optical coherence tomography; PCBV=percent change brain volume; PI=principal investigator; RRMS=relapsing-remitting MS; SAE=serious AE; SEE=standard errors of the coefficient estimate; SPMS=secondary progressive MS