Intranasal Glutathione in Parkinson's Disease

Study Overview
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Brief Summary
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Excessive free radical formation and depletion of the brain's primary antioxidant, glutathione, are established components of Parkinson's disease (PD) pathophysiology. While there is rationale for the therapeutic use of reduced glutathione (GSH) in PD, and even some preliminary evidence to suggest the use of GSH can lead to symptomatic improvement, obstacles surrounding currently employed delivery methods have hindered the clinical utility of this therapy. Intranasal GSH, (in)GSH, is a novel method of delivery for this popular CAM therapy in patients with PD, and bypasses the obstacles associated with other delivery methods. It has been used in clinical practice since 2005. The aim of this study is to evaluate safety, tolerability, and preliminary absorption data of (in)GSH in volunteers with PD in a Phase I single ascending dose escalation study.

Detailed Description
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Individuals will be randomized to one of three treatment (100 mg GSH/ ml, 200 mg GSH/ ml, or placebo) arms in a double-blind fashion. All study medication will be administered 1 ml three times daily for three months, with a one-month wash out.

Official Title
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A Phase 1 Study of Intranasal Reduced Glutathione in Parkinson's Disease

Conditions
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Parkinson's Disease (PD)

Intervention / Treatment
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* Drug: Intranasal glutathione - (in)GSH
* Drug: Intranasal glutathione - (in)GSH
* Drug: Saline Intranasal Delivery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Parkinson's Disease made by neurologist within previous 10 years Modified Hoehn and Yahr Stage <3 Age >20 Subjects must be able to attend study visits at screening, baseline, weeks 4, 8, 12, 16 Subjects must be able to demonstrate self-administration of study medication or have active caregiver who can administer daily. Dose and frequency of all pharmaceutical medications must be stable for one month prior to enrollment. Diet, exercise and supplementation must be kept constant throughout participation in study Ability to read and speak English Exclusion Criteria: Dementia as evidenced by Montreal Cognitive Assessment (MoCA) <24 Diseases with features common to Parkinson's Disease (eg. essential tremor, multiple system atrophy, progressive supranuclear palsy) Epilepsy History of stroke, CVA Elevated levels of ALT, AST, BUN or creatinine Chronic sinusitis as defined by SNOT-20 score >1.0 on items 1-10. Presence of other serious illness History of brain surgery History of structural brain damage History of intranasal telangiectasia Supplementation with glutathione and agents shown to increase glutathione will not be permitted and will require a 90 day washout period. Pregnant or at risk of becoming pregnant.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intranasal GSH 100mg/ml<br>Study participant will be provided with monthly supply of study medication and will be asked to intake 100mg/ml of intranasal glutathione (n=15) An amount of 1ml with a frequency 3x per days and duration of 12 weeks with a dosage of 2100mg | Drug: Intranasal glutathione - (in)GSH<br>* Intranasal glutathione-Tripeptide glutathione 100 mg/ml. 1 ml 3x per day TID X 12 weeks at 2100mg in 15 participants<br>|
| Active Comparator: Intranasal glutathione 200mg/ml<br>Study participant will be provided with monthly supply of study medication and will be asked to intake 200/ml of intranasal glutathione (n=15) An amount of 1ml with a frequency 3x per days and duration of 12 weeks with a dosage of 4200mg | Drug: Intranasal glutathione - (in)GSH<br>* Intranasal Glutathione-Tripeptide glutathione - 200mg/ml. 1 ml 3x per day TID X 12 weeks at 4200mg in 15 participants<br>|
| Placebo Comparator: Saline intranasal delivery<br>Study participant will be provided with monthly supply of study medication and will be asked to intake Intranasal saline delivery (n=15) An amount of 1ml with a frequency 3x per day with a duration of 12 weeks | Drug: Saline Intranasal Delivery<br>* Saline administration 1ml 3x/day 12 weeks in 15 participants<br>|
| No Intervention: Watchful waiting<br>No intervention, watchful waiting only (n=4) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Safety | 1a. Laboratory monitoring for adverse events will include CBC, ALT, AST, BUN, creatinine, uric acid, and urinalysis. Data will be collected throughout the 12-week intervention and at 1-mo following cessation of the study medication. 1b. Clinical adverse events will be measured using a daily patient diary and record score cards specifically screening for sinus irritation. Monitoring of Side Effects System (MOSES) will be used to screen for systemic and generalized adverse events. 1c. Effect on PD symptoms will be measured by the UPDRS to screen for accelerated disease activity. | 12 weeks | 
| Determination of Tolerability | Participants will be asked to keep a daily log and unused study medication will be measured at each clinical visit. Tolerability will be measured by frequency and severity of reported adverse events and withdrawal from study. The goal will be to identify the maximum tolerated dose (MTD) which will be defined as the highest dose achieving adherence, as defined as 80% of the group taking the prescribed dose 80% of the time. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of systemic absorption characteristics | Red blood cell GSH levels will be measured at baseline, 4 weeks, and 12 weeks. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Neuroprotection, Glutathione, Intranasal