Central Nervous System Uptake of Intranasal Glutathione in Parkinson's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- The concentration of metabolites before and after (in)GSH will be compared (change in mean GSH concentration)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.)
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Reduced Glutathione (Drug)
结局指标
主要结局
The concentration of metabolites before and after (in)GSH will be compared (change in mean GSH concentration)
时间窗: 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.
次要结局
- A ROC curve will be generated to compare MRS [glutathione] to peripheral measures of RBC glutathione.(15 minutes after administration)
研究者
Laurie Mischley
Project Appointment
University of Washington