Phase IIb Study of Intranasal Glutathione in Parkinson's Disease

Summary

Glutathione is an important nutrient for brain function and loss of glutathione has been implicated in Parkinson's disease. Glutathione is an antioxidant made in the body out of three amino acids, the nutrients that make up protein. This study will determine whether administration of either dose of glutathione, as a nasal spray, improves PD symptoms over time in a population of individuals with Parkinson's disease (PD).

Timeline

Start

2015-04

Primary completion

2016-03

Completion

2016-04

Publications

• Background Allen J. Inhaled glutathione for the prevention of air pollution-related health effects: a brief review. Altern Ther Health Med. 2008 May-Jun;14(3):42-4.
• Background Baker MA, Cerniglia GJ, Zaman A. Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples. Anal Biochem. 1990 Nov 1;190(2):360-5. doi: 10.1016/0003-2697(90)90208-q.
• Background Chinta SJ, Andersen JK. Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: implications for Parkinson's disease. Free Radic Biol Med. 2006 Nov 1;41(9):1442-8. doi: 10.1016/j.freeradbiomed.2006.08.002. Epub 2006 Aug 7.
• Background Dexter DT, Sian J, Rose S, Hindmarsh JG, Mann VM, Cooper JM, Wells FR, Daniel SE, Lees AJ, Schapira AH, et al. Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann Neurol. 1994 Jan;35(1):38-44. doi: 10.1002/ana.410350107.
• Background Eyer P, Podhradsky D. Evaluation of the micromethod for determination of glutathione using enzymatic cycling and Ellman's reagent. Anal Biochem. 1986 Feb 15;153(1):57-66. doi: 10.1016/0003-2697(86)90061-8.
• Background Schapira AH. Progress in neuroprotection in Parkinson's disease. Eur J Neurol. 2008 Apr;15 Suppl 1:5-13. doi: 10.1111/j.1468-1331.2008.02055.x.
• Background Schulz JB, Lindenau J, Seyfried J, Dichgans J. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem. 2000 Aug;267(16):4904-11. doi: 10.1046/j.1432-1327.2000.01595.x.
• Results Merkus P, Guchelaar HJ, Bosch DA, Merkus FW. Direct access of drugs to the human brain after intranasal drug administration? Neurology. 2003 May 27;60(10):1669-71. doi: 10.1212/01.wnl.0000067993.60735.77.
• Results Pearce RK, Owen A, Daniel S, Jenner P, Marsden CD. Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease. J Neural Transm (Vienna). 1997;104(6-7):661-77. doi: 10.1007/BF01291884.
• Results Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K, Youdim MB. Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem. 1989 Feb;52(2):515-20. doi: 10.1111/j.1471-4159.1989.tb09150.x.
• Results Sakhi AK, Russnes KM, Smeland S, Blomhoff R, Gundersen TE. Simultaneous quantification of reduced and oxidized glutathione in plasma using a two-dimensional chromatographic system with parallel porous graphitized carbon columns coupled with fluorescence and coulometric electrochemical detection. J Chromatogr A. 2006 Feb 3;1104(1-2):179-89. doi: 10.1016/j.chroma.2005.11.129.
• Results Sechi G, Deledda MG, Bua G, Satta WM, Deiana GA, Pes GM, Rosati G. Reduced intravenous glutathione in the treatment of early Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry. 1996 Oct;20(7):1159-70. doi: 10.1016/s0278-5846(96)00103-0.
• Results Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol. 1994 Sep;36(3):348-55. doi: 10.1002/ana.410360305.
• Results Sofic E, Lange KW, Jellinger K, Riederer P. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci Lett. 1992 Aug 17;142(2):128-30. doi: 10.1016/0304-3940(92)90355-b.
• Results Winter Y, Balzer-Geldsetzer M, Spottke A, Reese JP, Baum E, Klotsche J, Rieke J, Simonow A, Eggert K, Oertel WH, Dodel R. Longitudinal study of the socioeconomic burden of Parkinson's disease in Germany. Eur J Neurol. 2010 Sep;17(9):1156-1163. doi: 10.1111/j.1468-1331.2010.02984.x. Epub 2010 Mar 22.
• Results Wolfe TR, Hillman TA, Bossart PJ. The comparative risks of bacterial contamination between a venturi atomizer and a positive displacement atomizer. Am J Rhinol. 2002 Jul-Aug;16(4):181-6; discussion 186.

Drugs

Indications