A Safety and Efficacy Study of Carbidopa-levodopa in Patients With Macular Degeneration

Summary

From 3 large patient databases, patients diagnosed with AMD who have never taken levodopa(L-DOPA) containing medications have a mean age of diagnosis at 71 years. Patients who have been treated with L-DOPA containing medications have a mean age of diagnosis of AMD at 79 years. L-DOPA binds to GPR143 in the retinal pigment epithelium, and releases PEDF, which protects the retina and downregulates VEGF, which is the cause of neovascularization. The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with AMD, and measure the effects on surrogate functional biomarkers of AMD.

Timeline

Start

2019-09

Primary completion

2020-12

Completion

2020-12

Outcome

Outcome not reported

Stopped: “Decided to do studies in patients with AMD”

Publications

• Background Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004 Nov;82(11):844-51. Epub 2004 Dec 14.
• Background Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008 Jun 12;358(24):2606-17. doi: 10.1056/NEJMra0801537. No abstract available.
• Background Bressler SB, Munoz B, Solomon SD, West SK; Salisbury Eye Evaluation (SEE) Study Team. Racial differences in the prevalence of age-related macular degeneration: the Salisbury Eye Evaluation (SEE) Project. Arch Ophthalmol. 2008 Feb;126(2):241-5. doi: 10.1001/archophthalmol.2007.53.
• Background Nowacka B, Lubinski W, Honczarenko K, Potemkowski A, Safranow K. Ophthalmological features of Parkinson disease. Med Sci Monit. 2014 Nov 11;20:2243-9. doi: 10.12659/MSM.890861.
• Background Ferrara N. Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat Med. 2010 Oct;16(10):1107-11. doi: 10.1038/nm1010-1107. No abstract available.
• Background Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci. 2016 May;73(9):1765-86. doi: 10.1007/s00018-016-2147-8. Epub 2016 Feb 6.
• Background Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS. L-DOPA is an endogenous ligand for OA1. PLoS Biol. 2008 Sep 30;6(9):e236. doi: 10.1371/journal.pbio.0060236.
• Background Falk T, Congrove NR, Zhang S, McCourt AD, Sherman SJ, McKay BS. PEDF and VEGF-A output from human retinal pigment epithelial cells grown on novel microcarriers. J Biomed Biotechnol. 2012;2012:278932. doi: 10.1155/2012/278932. Epub 2012 Apr 2.
• Background Brilliant MH, Vaziri K, Connor TB Jr, Schwartz SG, Carroll JJ, McCarty CA, Schrodi SJ, Hebbring SJ, Kishor KS, Flynn HW Jr, Moshfeghi AA, Moshfeghi DM, Fini ME, McKay BS. Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration. Am J Med. 2016 Mar;129(3):292-8. doi: 10.1016/j.amjmed.2015.10.015. Epub 2015 Oct 30.
• Background Sinemet package insert (FDA approved).
• Background Chandramohan A, Stinnett SS, Petrowski JT, Schuman SG, Toth CA, Cousins SW, Lad EM. VISUAL FUNCTION MEASURES IN EARLY AND INTERMEDIATE AGE-RELATED MACULAR DEGENERATION. Retina. 2016 May;36(5):1021-31. doi: 10.1097/IAE.0000000000001002.
• Background Owsley C, McGwin G Jr, Clark ME, Jackson GR, Callahan MA, Kline LB, Witherspoon CD, Curcio CA. Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration. Ophthalmology. 2016 Feb;123(2):344-351. doi: 10.1016/j.ophtha.2015.09.041. Epub 2015 Oct 30.
• Background Wu Z, Ayton LN, Luu CD, Guymer RH. Longitudinal changes in microperimetry and low luminance visual acuity in age-related macular degeneration. JAMA Ophthalmol. 2015 Apr;133(4):442-8. doi: 10.1001/jamaophthalmol.2014.5963.
• Background Hongyang Zhang; Nizar Saleh Abdelfattah; David S Boyer; Srinivas R Sadda, Longitudinal Quantitative OCT Analysis of Drusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration, ARVO Annual Meeting Abstract, 2015.
• Background Finger RP, Chong E, McGuinness MB, Robman LD, Aung KZ, Giles G, Baird PN, Guymer RH. Reticular Pseudodrusen and Their Association with Age-Related Macular Degeneration: The Melbourne Collaborative Cohort Study. Ophthalmology. 2016 Mar;123(3):599-608. doi: 10.1016/j.ophtha.2015.10.029. Epub 2015 Dec 8.
• Background Owsley C, McGwin G, Jackson GR, Heimburger DC, Piyathilake CJ, Klein R, White MF, Kallies K. Effect of short-term, high-dose retinol on dark adaptation in aging and early age-related maculopathy. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1310-8. doi: 10.1167/iovs.05-1292.
• Background Westfall, T.C. and Westfall, D.P. Drugs Acting at Synaptic and Neuroeffector Junctions. Pharmacological Basis of Therapeutics, 11th Edition, 530-535, McGraw-Hill, 2006.
• Background Standaert, D.G. and Young, A.B. Treatment of Central Nervous System Degenerative Disorders. Pharmacological Basis of Therapeutics, 11th Edition, 530-535, McGraw-Hill, 2006.

Drugs

Indications