Phase IIb Study of Intranasal Glutathione in Parkinson's Disease

NCT ID: NCT02424708

Last Updated: 2016-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-30

Study Completion Date

2016-04-30

Brief Summary

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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).

Detailed Description

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The study begins with a pre-screening telephone interview. During this conversation participants will be asked a series of questions that will help us identify whether they are eligible for participation in this study. The pre-screening interview process will take approximately 10 minutes and will include all screening criteria that does not require clinical or laboratory examination

All routine research visits will take place at Bastyr University Campus (Kenmore, WA). Participants will be asked to schedule visits at approximately the same time of day each visit .If they are on medications, we would like them to take their medications as they normally would on the day of the visit. Participants will be randomly assigned to one of three different study groups- a low dose group, a high dose group, or a placebo group.

Study participants will invited to volunteer for two magnetic resonance imagine (MRI) scans as part of this study, an optional part of study participation. For those who volunteer and qualify, MRIs will be performed at the University of Washington Radiology Department early in the morning. One scan will be taken at baseline before taking glutathione and the second upon completion of the study medication. There will be a separate consent form for those who participate in the imaging portion of this study. Among the participants who volunteer, the first 15 to qualify for an MRI scan will be scheduled according to MRI availability.

If participants are enrolled in the study, they will be asked to keep a daily log of actual frequency of administration of study medication, if any, as well as any changes in their PD symptoms, any adverse events they might experience, and their general well-being. We are giving participants enough medication to last four weeks, until the date of their next appointment. The medication should be taken three times a day (morning, afternoon, and evening).

Visit 1- Baseline: (Approximately 1 hour)

* Urine sample
* Venipuncture (blood draw, (40 mL / \~3 Tbsp) to assess blood antioxidant status..
* Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS), which involves assessing degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.
* Participant will be taught how and when to administer the study medication and be given a 1-month supply.

Visit 2- Week 4 follow-up: (Approximately 1 hour)

* Urine sample
* Venipuncture (blood draw, (40 mL / \~3 Tbsp) to assess blood antioxidant status..
* Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) and Webster-Step Second test involve assessing degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.
* Participant will be asked to return any unused study medication and applicator tips from the first month of the study and be given the next 1-month supply.
* We will inquire about medication changes and collect medication use logs.

Visit 3- Week 8 follow-up: (Approximately 1/2 hour)

* Participant will be asked to return any unused study medication from the second month of the study and be given the next 1-month supply.
* We will inquire about medication changes and collect medication use logs.

Visit 4- Week 12 follow-up: (Approximately 1 hour)

* Urine sample
* Venipuncture (blood draw, (40 mL / \~3 Tbsp) to assess blood antioxidant status..
* Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) to assess degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.
* Participants will be asked to return any unused study medication from the third month of the study.
* We will inquire about medication changes and collect medication use logs.

Visit 5- Week 16 follow-up: (Approximately 1 hour)

This visit is included to determine whether there are any lasting effects of the study medication one month following discontinuation of use. The visit will include:

* Urine sample
* Venipuncture (blood draw, (40 mL / \~3 Tbsp) to assess blood antioxidant status..
* Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) which involves assessing degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.

Overall, approximately 5 hours will be required for study participation. Blood draws will occur at most, but not all visits, and will not exceed 4 Tbsp per month.

Conditions

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Parkinson's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Reduced Glutathione 100mg

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.

Group Type ACTIVE_COMPARATOR

Reduced Glutathione 100mg

Intervention Type 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.

Reduced Glutathione 200mg

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.

Group Type ACTIVE_COMPARATOR

Reduced Glutathione 200mg

Intervention Type 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.

Interventions

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Reduced Glutathione 100mg

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.

Intervention Type DRUG

Reduced Glutathione 200mg

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Other Intervention Names

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(in)GSH (in)GSH Saline

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role collaborator

Bastyr University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laurie K Mischley, NDMPHPhD(c)

Role: PRINCIPAL_INVESTIGATOR

Bastyr University

Locations

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Bastyr University

Kenmore, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 18517105 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2291479 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17023271 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8285590 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3963383 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18353131 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10931172 (View on PubMed)

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.

Reference Type RESULT
PMID: 12771261 (View on PubMed)

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.

Reference Type RESULT
PMID: 9444566 (View on PubMed)

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.

Reference Type RESULT
PMID: 2911028 (View on PubMed)

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.

Reference Type RESULT
PMID: 16376913 (View on PubMed)

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.

Reference Type RESULT
PMID: 8938817 (View on PubMed)

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.

Reference Type RESULT
PMID: 8080242 (View on PubMed)

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.

Reference Type RESULT
PMID: 1454205 (View on PubMed)

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.

Reference Type RESULT
PMID: 20345926 (View on PubMed)

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.

Reference Type RESULT
PMID: 12222941 (View on PubMed)

Other Identifiers

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14-1443

Identifier Type: -

Identifier Source: org_study_id

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