PMID- 32418846 OWN - NLM STAT- MEDLINE DCOM- 20210727 LR - 20210903 IS - 2468-6530 (Electronic) IS - 2468-6530 (Linking) VI - 4 IP - 9 DP - 2020 Sep TI - Orally Administered Alpha Lipoic Acid as a Treatment for Geographic Atrophy: A Randomized Clinical Trial. PG - 889-898 LID - S2468-6530(20)30121-4 [pii] LID - 10.1016/j.oret.2020.03.019 [doi] AB - 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. CI - Copyright (c) 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Kim, Benjamin J AU - Kim BJ AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: Benjamin.Kim@uphs.upenn.edu. FAU - Hunter, Allan AU - Hunter A AD - Oregon Eye Consultants, Eugene, Oregon. FAU - Brucker, Alexander J AU - Brucker AJ AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Hahn, Paul AU - Hahn P AD - New Jersey Retina, Teaneck, New Jersey. FAU - Gehrs, Karen AU - Gehrs K AD - Department of Ophthalmology, University of Iowa, Iowa City, Iowa. FAU - Patel, Apurva AU - Patel A AD - Retina Northwest, Portland, Oregon. FAU - Edwards, Albert O AU - Edwards AO AD - Oregon Retina, Eugene, Oregon. FAU - Li, Yafeng AU - Li Y AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Khurana, Rahul N AU - Khurana RN AD - Northern California Retina Vitreous Associates, Mountain View, California. FAU - Nissim, Itzhak AU - Nissim I AD - Division of Genetics and Metabolic Disease, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Daniel, Ebenezer AU - Daniel E AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Grunwald, Juan AU - Grunwald J AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Ying, Gui-Shuang AU - Ying GS AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Pistilli, Maxwell AU - Pistilli M AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Maguire, Maureen G AU - Maguire MG AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Dunaief, Joshua L AU - Dunaief JL AD - Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. LA - eng GR - P30 EY001583/EY/NEI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200402 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 RN - 0 (Antioxidants) RN - 73Y7P0K73Y (Thioctic Acid) SB - IM MH - Administration, Oral MH - Aged MH - Aged, 80 and over MH - Antioxidants/administration & dosage MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Fluorescein Angiography/*methods MH - Fundus Oculi MH - Geographic Atrophy/diagnosis/*drug therapy MH - Humans MH - Male MH - Prospective Studies MH - Thioctic Acid/*administration & dosage MH - Treatment Outcome MH - *Visual Acuity PMC - PMC7483261 MID - NIHMS1582353 COIS- Conflicts of Interest B.J.K. reports being a consultant to Synergy Research, Inc., Apellis Pharmaceuticals, and Allergan. P.H. reports being a consultant for Alcon, Allergan, DORC, Genentech, and Zeiss; and is a speaker for Genentech. M.G.M. reports payments from Genentech/Roche for membership on data monitoring committees. R.N.K serves as a consultant for Allergan, Genentech, and Regeneron; and has grant support from Allergan, Chengdu Kanghong, Clearside Biomedical, Roche, and Santen. G.S.Y. reports payment for being a biostatistical consultant to Chengdu Kanghong Biotech Ltd., and for being a member of Data Safety Monitoring Committee for Synergy Research Inc. No conflicting relationship exists for any other authors. EDAT- 2020/05/19 06:00 MHDA- 2021/07/28 06:00 PMCR- 2021/09/01 CRDT- 2020/05/19 06:00 PHST- 2020/01/26 00:00 [received] PHST- 2020/03/15 00:00 [revised] PHST- 2020/03/23 00:00 [accepted] PHST- 2020/05/19 06:00 [pubmed] PHST- 2021/07/28 06:00 [medline] PHST- 2020/05/19 06:00 [entrez] PHST- 2021/09/01 00:00 [pmc-release] AID - S2468-6530(20)30121-4 [pii] AID - 10.1016/j.oret.2020.03.019 [doi] PST - ppublish SO - Ophthalmol Retina. 2020 Sep;4(9):889-898. doi: 10.1016/j.oret.2020.03.019. Epub 2020 Apr 2.