Central Nervous System Uptake of Intranasal Glutathione in Parkinson's Disease
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- University of Washington
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- The concentration of metabolites before and after (in)GSH will be compared (change in mean GSH concentration)
Study Overview
Brief Summary
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 glutathione augmentation. The aim of this study is to evaluate whether 200 mg of (in)GSH results in measurable changes in brain glutathione concentrations, as measured by magnetic resonance spectroscopy (MRS) in 15 individuals with PD.
Detailed Description
Objectives
Primary Aim: To determine whether intranasal reduced glutathione, (in)GSH, is capable of augmenting CNS glutathione levels.
Hypothesis: Mean MRS glutathione concentration will rise from baseline following administration of 1 cc 200 mg/ml (in)GSH.
Design and Outcomes:
This pilot study seeks to obtain baseline data regarding the feasibility of MRS to detect a change in CNS glutathione concentration following administration of 200 mg (in)GSH. CNS glutathione levels will be measured using magnetic resonance spectroscopy (MRS), with the putamen as the region of interest. Baseline brain GSH concentrations will be measured by MRS at approximately the same time each day in all individuals before and after administration of study medication.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age > 18 years.
- •Ability to attend a 3 hour study visit in Seattle, WA.
- •Ability to read and speak English.
- •Have three or more of the required positive criteria for PD from Step 3 of the UK Brain Bank Diagnostic Criteria for Parkinson's Disease.
- •A modified Hoehn & Yahr Stage 2-
- •(bilateral disease, not severely disabled.)
Exclusion Criteria
- •Any contra-indication to magnetic resonance imaging, including pacemaker, pacemaker wires, aneurysm clip, or any electronic implant, weight over 136 kg (300 lb), metal embedded in soft tissue or in the eye, prosthetic eye, claustrophobia, substance abuse, use of recreational drugs, pregnancy, or other medical contraindications.
- •A history of epilepsy, stroke, brain surgery, or structural brain disease.
- •The presence of other serious illnesses (discretion of study clinician, e.g. concurrent cancer treatment.)
- •Pregnant.
- •A history of sulfur sensitivity, e.g. reaction N-acetylcysteine, MSM, SAMe.
- •A recent history of asthma.
- •Supplementation with glutathione (oral, intravenous, intranasal, or nebulized) or the glutathione precursor, N-acetylcysteine, for six months prior to baseline study visit.
- •History of sensitivity to sulfur containing medications/ supplements, i.e. NAC, MSM.
- •Current drug or alcohol use or dependence.
- •Inability/unwillingness to provide informed consent. (e.g. diagnosis of dementia, confusion about study goals or participation.)
- •Acute infection (e.g. upper respiratory, dermal) in the previous 30 days.
- •Diagnosis of any mental illness, ever. (Mental illness has been associated with glutathione depletion.)
- •Diagnosis of any chronic disease, ever. (e.g. Hep C, autoimmune disease, etc.)
- •Head tremor or head dyskinesia that cannot be comfortably controlled for 90 minutes.
Arms & Interventions
Reduced Glutathione
The study medication is packaged in sterile 1 ml pre-filled syringes, each containing 200 mg/ ml of reduced glutathione (GSH), which will be delivered intranasally.
Intervention: Reduced Glutathione (Drug)
Outcomes
Primary Outcomes
The concentration of metabolites before and after (in)GSH will be compared (change in mean GSH concentration)
Time Frame: 15 minutes after administration
Describe the change in mean GSH concentration following administration of (in)GSH. The data analysis will be ipsative- results will be reported as percent change from the individual's own baseline GSH concentration.
Secondary Outcomes
- A ROC curve will be generated to compare MRS [glutathione] to peripheral measures of RBC glutathione.(15 minutes after administration)
Investigators
Laurie Mischley
Project Appointment
University of Washington