CNS Uptake of Intranasal Glutathione

Sponsor

University of Washington (Other)

Overall Status

Completed

CT.gov ID

NCT02324426

Collaborator

Michael J. Fox Foundation for Parkinson's Research (Other)

Enrollment

Location

Arm

Duration (Months)

5.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Reduced Glutathione	Phase 1

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.

Outcome Measure: 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.

Interventions and Duration:

If a participant communicates he/she understands the study, meets inclusion criteria, and provides informed consent, individuals will be scheduled for a single visit at the University of Washington for MR imaging (MRI), clinical evaluation, and blood draw. (~ 3 hours). Participants will be asked to be optimally medicated at the time of study visit, to the best of their ability.

Sample Size and Population:

This is a proof-of-concept pilot trial. Based on the data from the single test subject, a sample size of 15 would provide 80% power to detect an increase in CNS glutathione concentrations between pre- and post- administration values, if we are willing to accept an alpha value of 0.2.

1.1 Primary Aims

Primary Aim: To determine whether intranasal reduced glutathione, (in)GSH, is capable of augmenting CNS glutathione concentration. (Region of Interest: putamen)

Hypothesis: Mean MRS glutathione concentration will rise from baseline approximately 15 minutes following administration of 200 mg/ml (in)GSH in 1 cc saline.

1.2 Secondary Objectives

Hypothesis: Baseline CNS glutathione concentrations and RBC glutathione concentrations will be correlated.

To determine whether brain MRS [glutathione] and red blood cell (RBC) glutathione levels are correlated.

Outcome: A ROC curve will be drawn between mean brain [glutathione] and RBC total glutathione.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Central Nervous System Uptake of Intranasal Glutathione in Parkinson's Disease

Study Start Date :

Dec 1, 2014

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Reduced Glutathione 200 mg GSH delivered in 1 cc sterile saline using a syringe with a Mucosal Atomization Device (MAD) tip. Other Names: (in)GSH

Arm

Intervention/Treatment

Experimental: 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.

Drug: Reduced Glutathione

200 mg GSH delivered in 1 cc sterile saline using a syringe with a Mucosal Atomization Device (MAD) tip.

Other Names:

(in)GSH

Outcome Measures

Primary Outcome Measures

The concentration of metabolites before and after (in)GSH will be compared (change in mean GSH concentration) [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 Outcome Measures

A ROC curve will be generated to compare MRS [glutathione] to peripheral measures of RBC glutathione. [15 minutes after administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 2-3. (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.