Orally Administered Alpha Lipoic Acid as a Treatment for Geographic Atrophy: A Randomized Clinical Trial.

Purpose: Alpha lipoic acid (ALA) is a nutraceutical and potent antioxidant that has shown efficacy in the retina light damage mouse model and in humans for multiple sclerosis. Our objective was to evaluate the efficacy and safety of oral ALA for the treatment of geographic atrophy (GA).

Design: Randomized, controlled, double-masked, multicenter phase 2 clinical trial of ALA versus placebo.

Participants: Participants with unilateral or bilateral GA from age-related macular degeneration.

Methods: Participants were randomized to 1200 mg daily of ALA or placebo. Fundus autofluorescence, fundus color photography, and spectral-domain OCT were conducted and best-corrected visual acuity (BCVA) was obtained at baseline and every 6 months through month 18.

Main Outcome Measures: Annual rate of change over 18 months in square root-transformed area of GA in study eyes as measured on fundus autofluorescence. Secondary outcomes included the number of adverse events (AEs), change in BCVA, and annual rate of change in area of GA measured on color photographs.

Results: Fifty-three participants (mean age, 80 years) were randomized (April 2016-August 2017). Twenty-seven participants (37 eyes) were in the placebo group, and 26 participants (36 eyes) were in the ALA group. Unadjusted mean (standard error) annual change in GA area was 0.28 (0.02) mm and 0.31 (0.02) mm for the placebo and ALA groups, respectively (difference, 0.04 mm; 95% confidence interval [CI], -0.03 to 0.11 mm; P = 0.30). Adjusting for baseline GA area, number of GA lesions, and presence of subfoveal GA, the mean annual change in GA area was 0.27 (0.04) mm and 0.32 (0.05) mm for the placebo and ALA groups, respectively (difference, 0.05 mm; 95% CI, -0.02 to 0.12 mm; P = 0.14). At 18 months, the percent of eyes losing 15 letters or more of BCVA was 22% (8 of 36) and 14% (5 of 36) in the placebo and ALA groups, respectively (P = 0.54). No difference was found in the percentage of participants with nonserious AEs (P = 0.96) or serious AEs (P = 0.28) between the placebo and ALA groups.

Conclusions: Results do not support ALA having beneficial effects on GA or BCVA. This trial design may be useful for other GA repurposing drug trials.