Phase IIb Study of Intranasal Glutathione in Parkinson's Disease

NCT02424708 | Completed Phase 2

• 1 other identifier: 14-1443
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Parkinson's Disease

Keywords

Reduced Glutathione; Intranasal; (in)GSH; Parkinson's Disease; Glutathione; Uptake; central nervous system

Outcome Measures

Primary Outcomes (1)

• Change in Unified Parkinson's Disease Rating Scale (UPDRS) Score

  12 weeks

Secondary Outcomes (1)

• Red blood cell (RBC) GSH levels will be measured at baseline, week 4, week 12, and 16.

  up to 16 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

The study medication is packaged in sterile 1 ml pre-filled syringes, containing saline, which will be delivered intranasally.

Drug: Placebo

Reduced Glutathione 100mg

ACTIVE COMPARATOR

The study medication is packaged in sterile 1 ml pre-filled syringes, containing 100 mg/ml of reduced glutathione (GSH), which will be delivered intranasally.

Drug: Reduced Glutathione 100mg

Reduced Glutathione 200mg

ACTIVE COMPARATOR

The study medication is packaged in sterile 1 ml pre-filled syringes, containing 200 mg/ml of reduced glutathione (GSH), which will be delivered intranasally.

Drug: Reduced Glutathione 200mg

Interventions

Reduced Glutathione 100mg DRUG

100mg GSH delivered intranasally, three times a day for 12 weeks, in 1 cc sterile saline using a syringe with a Mucosal Atomization Device (MAD) tip.

Also known as: (in)GSH

Reduced Glutathione 100mg

Reduced Glutathione 200mg DRUG

200mg GSH delivered intranasally, three times a day for 12 weeks, in 1 cc sterile saline using a syringe with a Mucosal Atomization Device (MAD) tip.

Also known as: (in)GSH

Reduced Glutathione 200mg

Placebo DRUG

Saline delivered intranasally, three times a day for 12 weeks, in 1 cc sterile saline using a syringe with a Mucosal Atomization Device (MAD) tip.

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PD made by a clinical neurologist within the previous 10 years
• A modified Hoehn \& Yahr Stage \<3
• Age \>21
• Subjects must be able to attend study visits at baseline, weeks 4, 8, 12, and 16.
• Subjects must be able to demonstrate, or have a caregiver administer, medication.
• Dose and frequency of pharmaceutical medications must be stable for 1 month prior to enrollment.
• Dose and frequency of naturopathic medications must be stable for 1 month prior to enrollment.
• Diet, exercise, and medications must be kept constant throughout participation in the study. (Medication changes considered essential by a participant's physician will be permitted and recorded).
• Ability to read and speak English.

You may not qualify if:

• Dementia as evidenced by a Montreal Cognitive Assessment score of less than 24.
• Diseases with features common to PD (e.g., essential tremor, multiple system atrophy, progressive supranuclear palsy)
• Epilepsy
• A history of stroke
• The presence of other serious illnesses
• Respiratory disease (e.g. asthma, COPD)
• A history of brain surgery
• A history of structural brain disease
• A history of intranasal telangiectasia
• Supplementation with glutathione, and agents shown to increase glutathione, will not be permitted and their use will necessitate a 90-day washout period; this will be required for all forms of glutathione and the glutathione precursor, N-acetylcysteine.
• Pregnant or at risk of becoming pregnant (i.e., unwilling to use birth control if a sexually active, pre-menopausal female). Urine pregnancy tests will be administered to pre-menopausal women.

Sponsors & Collaborators

• Bastyr University: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (2)

Bastyr University

Kenmore, Washington, 98028, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (16)

• 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.

  PMID: 18517105 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.

  PMID: 2291479 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.

  PMID: 17023271 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.

  PMID: 8285590 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.

  PMID: 3963383 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.

  PMID: 18353131 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.

  PMID: 10931172 BACKGROUND

• 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.

  PMID: 12771261 RESULT

• 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.

  PMID: 9444566 RESULT

• 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.

  PMID: 2911028 RESULT

• 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.

  PMID: 16376913 RESULT

• 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.

  PMID: 8938817 RESULT

• 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.

  PMID: 8080242 RESULT

• 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.

  PMID: 1454205 RESULT

• 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.

  PMID: 20345926 RESULT

• 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.

  PMID: 12222941 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

Glutathione; Sodium Chloride

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Laurie K Mischley, NDMPHPhD(c)

  Bastyr University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 23, 2015
• Study Start: April 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2016
• Last Updated: June 24, 2016

Record last verified: 2016-06

Locations

US (2)