Measures of Mitochondria Dysfunction in PD

Study Overview
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Brief Summary
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This study evaluates metabolic and functional parameters in the skeletal muscle of Parkinson's disease patients for comparison to a set of healthy age-matched controls.

Detailed Description
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The goal of this study is to identify the unique signature of bioenergetic markers and mitochondrial (dys)function in muscle of individuals with PD, who are 65-85 of age, read and speak English, have a Hoehn & Yahr score between 2 and 3 (bilateral disease, not severely disabled) and have a clinical diagnosis of PD. Bioenergetic markers and muscle functional properties will be compared to a control dataset collected over the last few years from healthy elderly subjects in the same age range to provide a foundation for future intervention studies.

Official Title
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Functional and Metabolomic Biomarkers of Mitochondrial Dysfunction in Parkinson's Disease

Conditions
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Parkinson Disease, Mitochondrial

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65-85 years. Ability to attend a 3-hour study visit in Seattle, WA. Ability to read and speak English. Hoehn & Yahr Stage 2-3. (bilateral disease, not severely disabled.) Exclusion Criteria: Any contra-indication to magnetic resonance imaging A history of epilepsy, stroke, brain surgery, or structural brain disease. The presence of other serious illnesses Current or recent enrollment in a clinical trial involving an investigational product or device. Supplementation with NAD, nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and other nutraceuticals designed to target NAD for 30 days prior to baseline study visit. 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. Right limb tremor or dyskinesia that cannot be comfortably controlled for 90 minutes.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ATPmax | Maximal mitochondrial ATP production rates measured by magnetic resonance spectroscopy | baseline | 
| NAD(H) metabolites | Measurement of relative NAD(H) metabolite concentrations in resting skeletal muscle by magnetic resonance spectroscopy | baseline | 
| Muscle force and endurance | Maximum voluntary contraction (MVC) force in Newtons and fatigue resistance assessed by the ability to maintain repeated contractions at 70% MVC will be measured in the hand (flexor digitorum interroseus) and leg (tibialis anterior) using isometric contractions in a custom made apparatus. | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitochondrial metabolites | Separate measurement of NAD(H) metabolite concentrations in cytosol and mitochondria by magnetic resonance spectroscopy in resting skeletal muscle | baseline | 
| Relationship between self report function and mitochondrial energetics | Correlation between self report of fatigue, balance, and muscle pain (PRO-PD) with ATPmax rates and NAD(H) metabolite concentrations measured using magnetic resonance spectroscopy. | baseline | 
| Relationship between clinical assessment and mitochondrial energetics | Correlation between UPDRS with ATPmax and NAD(H) metabolites | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, Mitochondria, Skeletal Muscle, Bioenergetics