A Study to Evaluate the Safety and Efficacy of RQC for AMD

Summary

To evaluate the safety and efficacy of resveratrol, quercetin, and curcumin in combination (RQC) over 2 years in patients with age-related macular degeneration (AMD).

Timeline

Start

2021-10-04

Primary completion

2024-11-07

Completion

2024-11-07

Publications

• Background Almeida L, Vaz-da-Silva M, Falcao A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P. Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res. 2009 May;53 Suppl 1:S7-15. doi: 10.1002/mnfr.200800177.
• Background Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron. 2012 Jul 12;75(1):26-39. doi: 10.1016/j.neuron.2012.06.018.
• Background Barratt-Due A, Pischke SE, Nilsson PH, Espevik T, Mollnes TE. Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets. J Leukoc Biol. 2017 Jan;101(1):193-204. doi: 10.1189/jlb.3VMR0316-132R. Epub 2016 Aug 31.
• Background Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1246-52. doi: 10.1158/1055-9965.EPI-07-0022.
• Background Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, Brenner DE. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010 Nov 15;70(22):9003-11. doi: 10.1158/0008-5472.CAN-10-2364. Epub 2010 Oct 8.
• Background Byun EB, Yang MS, Choi HG, Sung NY, Song DS, Sin SJ, Byun EH. Quercetin negatively regulates TLR4 signaling induced by lipopolysaccharide through Tollip expression. Biochem Biophys Res Commun. 2013 Feb 22;431(4):698-705. doi: 10.1016/j.bbrc.2013.01.056. Epub 2013 Jan 24.
• Background Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8. doi: 10.1089/107555303321223035.
• Background Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.
• Background AREDS2 Research Group; Chew EY, Clemons T, SanGiovanni JP, Danis R, Domalpally A, McBee W, Sperduto R, Ferris FL. The Age-Related Eye Disease Study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Ophthalmology. 2012 Nov;119(11):2282-9. doi: 10.1016/j.ophtha.2012.05.027. Epub 2012 Jul 26.
• Background Chew EY, Lindblad AS, Clemons T; Age-Related Eye Disease Study Research Group. Summary results and recommendations from the age-related eye disease study. Arch Ophthalmol. 2009 Dec;127(12):1678-9. doi: 10.1001/archophthalmol.2009.312. No abstract available.
• Background Cottart CH, Nivet-Antoine V, Beaudeux JL. Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans. Mol Nutr Food Res. 2014 Jan;58(1):7-21. doi: 10.1002/mnfr.201200589. Epub 2013 Jun 6.
• Background Davis MD, Gangnon RE, Lee LY, Hubbard LD, Klein BE, Klein R, Ferris FL, Bressler SB, Milton RC; Age-Related Eye Disease Study Group. The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17. Arch Ophthalmol. 2005 Nov;123(11):1484-98. doi: 10.1001/archopht.123.11.1484.
• Background Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, Ng CS, Badmaev V, Kurzrock R. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008 Jul 15;14(14):4491-9. doi: 10.1158/1078-0432.CCR-08-0024.
• Background Egert S, Wolffram S, Bosy-Westphal A, Boesch-Saadatmandi C, Wagner AE, Frank J, Rimbach G, Mueller MJ. Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr. 2008 Sep;138(9):1615-21. doi: 10.1093/jn/138.9.1615.
• Background Ferris FL 3rd, Bailey I. Standardizing the measurement of visual acuity for clinical research studies: Guidelines from the Eye Care Technology Forum. Ophthalmology. 1996 Jan;103(1):181-2. doi: 10.1016/s0161-6420(96)30742-2. No abstract available.
• Background Ferris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR; Beckman Initiative for Macular Research Classification Committee. Clinical classification of age-related macular degeneration. Ophthalmology. 2013 Apr;120(4):844-51. doi: 10.1016/j.ophtha.2012.10.036. Epub 2013 Jan 16.
• Background Ferry DR, Smith A, Malkhandi J, Fyfe DW, deTakats PG, Anderson D, Baker J, Kerr DJ. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996 Apr;2(4):659-68.
• Background Feuer WJ, Yehoshua Z, Gregori G, Penha FM, Chew EY, Ferris FL, Clemons TE, Lindblad AS, Rosenfeld PJ. Square root transformation of geographic atrophy area measurements to eliminate dependence of growth rates on baseline lesion measurements: a reanalysis of age-related eye disease study report no. 26. JAMA Ophthalmol. 2013 Jan;131(1):110-1. doi: 10.1001/jamaophthalmol.2013.572. No abstract available.
• Background Gradisar H, Keber MM, Pristovsek P, Jerala R. MD-2 as the target of curcumin in the inhibition of response to LPS. J Leukoc Biol. 2007 Oct;82(4):968-74. doi: 10.1189/jlb.1206727. Epub 2007 Jul 3.
• Background Grunwald JE, Pistilli M, Ying GS, Maguire MG, Daniel E, Martin DF; Comparison of Age-related Macular Degeneration Treatments Trials Research Group. Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2015 Apr;122(4):809-16. doi: 10.1016/j.ophtha.2014.11.007. Epub 2014 Dec 24.
• Background Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013 Jan;15(1):195-218. doi: 10.1208/s12248-012-9432-8. Epub 2012 Nov 10.
• Background Handa JT, Bowes Rickman C, Dick AD, Gorin MB, Miller JW, Toth CA, Ueffing M, Zarbin M, Farrer LA. A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration. Nat Commun. 2019 Jul 26;10(1):3347. doi: 10.1038/s41467-019-11262-1.
• Background Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017 Oct 22;6(10):92. doi: 10.3390/foods6100092.
• Background Jobin C, Bradham CA, Russo MP, Juma B, Narula AS, Brenner DA, Sartor RB. Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J Immunol. 1999 Sep 15;163(6):3474-83.
• Background Keenan TD, Agron E, Domalpally A, Clemons TE, van Asten F, Wong WT, Danis RG, Sadda S, Rosenfeld PJ, Klein ML, Ratnapriya R, Swaroop A, Ferris FL 3rd, Chew EY; AREDS2 Research Group. Progression of Geographic Atrophy in Age-related Macular Degeneration: AREDS2 Report Number 16. Ophthalmology. 2018 Dec;125(12):1913-1928. doi: 10.1016/j.ophtha.2018.05.028. Epub 2018 Jul 27.
• Background la Porte C, Voduc N, Zhang G, Seguin I, Tardiff D, Singhal N, Cameron DW. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet. 2010 Jul;49(7):449-54. doi: 10.2165/11531820-000000000-00000.
• Background Merle NS, Paule R, Leon J, Daugan M, Robe-Rybkine T, Poillerat V, Torset C, Fremeaux-Bacchi V, Dimitrov JD, Roumenina LT. P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4/heme-dependent manner. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6280-6285. doi: 10.1073/pnas.1814797116. Epub 2019 Mar 8.
• Background Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vis (Lond). 2016 Dec 22;3:34. doi: 10.1186/s40662-016-0063-5. eCollection 2016.
• Background Seddon JM, Silver RE, Kwong M, Rosner B. Risk Prediction for Progression of Macular Degeneration: 10 Common and Rare Genetic Variants, Demographic, Environmental, and Macular Covariates. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2192-202. doi: 10.1167/iovs.14-15841.
• Background Suresh K. An overview of randomization techniques: An unbiased assessment of outcome in clinical research. J Hum Reprod Sci. 2011 Jan;4(1):8-11. doi: 10.4103/0974-1208.82352.
• Background Vadhan-Raj S, Weber DM, Wang M, Giralt SA, Thomas SK, Alexanian R, Zhou X, Patel P, Bueso-Ramos CE, Newman RA, Aggarwal BB. Curcumin downregulates NF-kB and related genes in patients with multiple myeloma: results of a phase I/II study. Blood. 2007;110(11):1177.
• Background Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014 Feb;2(2):e106-16. doi: 10.1016/S2214-109X(13)70145-1. Epub 2014 Jan 3.
• Background Youn HS, Lee JY, Fitzgerald KA, Young HA, Akira S, Hwang DH. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. J Immunol. 2005 Sep 1;175(5):3339-46. doi: 10.4049/jimmunol.175.5.3339.
• Background Youn HS, Saitoh SI, Miyake K, Hwang DH. Inhibition of homodimerization of Toll-like receptor 4 by curcumin. Biochem Pharmacol. 2006 Jun 28;72(1):62-9. doi: 10.1016/j.bcp.2006.03.022. Epub 2006 Apr 1.
• Background Koronyo Y, Biggs D, Barron E, Boyer DS, Pearlman JA, Au WJ, Kile SJ, Blanco A, Fuchs DT, Ashfaq A, Frautschy S, Cole GM, Miller CA, Hinton DR, Verdooner SR, Black KL, Koronyo-Hamaoui M. Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease. JCI Insight. 2017 Aug 17;2(16):e93621. doi: 10.1172/jci.insight.93621. eCollection 2017 Aug 17.
• Background Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Miller CA, Ko MK, Black KL, Schwartz M, Farkas DL. Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage. 2011 Jan;54 Suppl 1:S204-17. doi: 10.1016/j.neuroimage.2010.06.020. Epub 2010 Jun 13.

Drugs

Indications