CNS Uptake of Intranasal Glutathione

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02324426
• Other study ID #: 48273-A
• Status: Completed
• Phase: Phase 1
• First received: December 4, 2014
• Last updated: April 29, 2015
• Start date: December 2014
• Est. completion date: March 2015

Study information

• Verified date: March 2015
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

1. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

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

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Michael J. Fox Foundation for Parkinson's Research

Country where clinical trial is conducted

United States, 

References & Publications (23)

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Mischley LK SL, Samii A, Pollisar N, Lau R, Leverenz J, . Phase I Study of Intranasal Glutathione in Parkinson's Disease. Seattle: Bastyr University Research Instittue; 2013.

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Mischley, L. Glutathione Deficiency in Parkinson's Disease: Intranasal Administration as a Method of Augmentation. Journal of Orthomolecular Medicine 26(1):32-36, 2011.

Mullins PG, McGonigle DJ, O'Gorman RL, Puts NA, Vidyasagar R, Evans CJ; Cardiff Symposium on MRS of GABA, Edden RA. Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. Neuroimage. 2014 Feb 1;86:43-52. doi: 10.1016/j.neuroimage.2012.12.004. Epub 2012 Dec 13. Review. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The concentration of metabolites before and after (in)GSH will be compared (change in mean GSH concentration)	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.	15 minutes after administration	No
Secondary	A ROC curve will be generated to compare MRS [glutathione] to peripheral measures of RBC glutathione.		15 minutes after administration	No