A randomized, double-blind phase I/IIa study of intranasal glutathione in Parkinson's disease.

BACKGROUND: Depletion of reduced glutathione is associated with PD and glutathione augmentation has been proposed as a disease-modifying strategy. The aim of this study was to determine the safety and tolerability of intranasal reduced glutathione in individuals with PD. METHODS: Thirty individuals with PD were randomized to either placebo (saline), 300 mg/day, or 600 mg/day of intranasal glutathione in three divided daily doses. Follow-up visits included side effect screening of PD symptoms and cognition, blood chemistry, sinus irritation, and hyposmia. Tolerability was measured by frequency and severity of reported adverse events, compliance, and withdrawals from the study. RESULTS: After 3 months, there were no substantial differences between groups in the number of adverse events reported or observed among all safety measures assessed. All groups met tolerability criteria. CONCLUSIONS: These data support the safety and tolerability of intranasal glutathione in this population. Pharmacokinetic and dose-finding studies are warranted.

Use of a self-rating scale of the nature and severity of symptoms in Parkinson's Disease (PRO-PD): Correlation with quality of life and existing scales of disease severity.

A self-rating scale was developed to permit patient-reported, remote assessment of Parkinson's disease symptom severity. The goal was to create a continuous outcome measure that does not require a clinical exam, does not fluctuate in response to dopaminergic medications, takes only a few minutes to complete, allows for stratification by symptom(s), and captures both motor and non-motor Parkinson's disease symptoms, major contributors to quality of life. The Patient Reported Outcomes in Parkinson's Disease (PRO-PD) is the cumulative score of 32 slider bars, each evaluating a common Parkinson's disease symptom. The PRO-PD has been used as an outcome measure in three studies. The baseline data from each of these studies were pooled for this analysis. Symptom frequency and severity are described, as well as correlation coefficients with existing measures of Parkinson's disease severity. Data on 1031 participants with Parkinson's disease were available for analysis. Fatigue, impaired handwriting, daytime sleepiness, slowness, tremor, muscle cramps, and forgetfulness were the most frequently reported symptoms. Persons with a relatively long duration of Parkinson's disease tended to report more, and more severe, symptoms. The PRO-PD was most highly correlated with the Parkinson's Disease Questionaire-39 (r = 0.763, P < 0.000) and Patient-Reported Outcome Measurement Information System Global quality of life (r = -0.7293, P < 0.000), other patient-reported quality of life measures. The PRO-PDnon-motor subset was highly correlated with the Non-Motor Symptom Score (r = 0.7533, P < 0.000). There was a moderate correlation seen with Hoehn & Yahr (r = 0.5922, P < 0.000), total Unified Parkinson's disease Rating Scale (r = 0.4724, P < 0.000), and the Timed-Up-&-Go (r = 0.4709, P < 0.000). The PRO-PD may have utility for patients, providers, and researchers as a patient-centered measure of Parkinson's disease symptom severity. Further PRO-PD validation efforts are warranted.

Role of Diet and Nutritional Supplements in Parkinson's Disease Progression.

OBJECTIVES: The goal of this study is to describe modifiable lifestyle variables associated with reduced rate of Parkinson's disease (PD) progression. METHODS: The patient-reported outcomes in PD (PRO-PD) were used as the primary outcome measure, and a food frequency questionnaire (FFQ) was used to assess dietary intake. In this cross-sectional analysis, regression analysis was performed on baseline data to identify the nutritional and pharmacological interventions associated with the rate of PD progression. All analyses were adjusted for age, gender, and years since diagnosis. RESULTS: 1053 individuals with self-reported idiopathic PD were available for analysis. Foods associated with the reduced rate of PD progression included fresh vegetables, fresh fruit, nuts and seeds, nonfried fish, olive oil, wine, coconut oil, fresh herbs, and spices (P < 0.05). Foods associated with more rapid PD progression include canned fruits and vegetables, diet and nondiet soda, fried foods, beef, ice cream, yogurt, and cheese (P < 0.05). Nutritional supplements coenzyme Q10 and fish oil were associated with reduced PD progression (P = 0.026 and P = 0.019, resp.), and iron supplementation was associated with faster progression (P = 0.022). DISCUSSION: These are the first data to provide evidence that targeted nutrition is associated with the rate of PD progression.

Phase IIb Study of Intranasal Glutathione in Parkinson's Disease.

BACKGROUND: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson's disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD. OBJECTIVE: This Phase IIb study was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH, for symptomatic relief is warranted and to determine the most appropriate trial design for a disease-modification study. METHODS: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1-3 PD. Participants were randomized to receive intranasal placebo (saline), 100 mg GSH, or 200 mg GSH thrice daily for three months, and were observed over a one-month washout period. RESULTS: All cohorts improved over the intervention period, including placebo. The high-dose group demonstrated improvement in total Unified PD Rating Scale (UPDRS) (-4.6 (4.7), P = 0.0025) and UPDRS motor subscore (-2.2 (3.8), P = 0.0485) over baseline, although neither treatment group was superior to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy. CONCLUSIONS: Although predicted improvements in PD total and motor scores were observed, these data do not suggest (in)GSH is superior to placebo after a three month intervention. The symptomatic effects are sufficient to warrant a delayed-start or wash-out design study for disease-modification trials. Whether long-term use of (in)GSH leads to clinical improvements that are sustained and significantly different than placebo will require appropriately-powered longer-duration studies in larger cohorts. The improvement in the placebo arm was more robust than has been observed in previous PD studies and warrants further investigation.