Safety and Effectiveness of Intermittent Hypoxia Treatment in Parkinson's Disease

Study Overview
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Brief Summary
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To explore the safety, feasibility and net symptomatic effects of multiple (3x/week, for 4 weeks) intermittent hypoxia treatment sessions in individuals with PD. Secondary outcomes include exploring induction of relevant neuroprotective pathways as measured in serum.

Detailed Description
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Intermittent hypoxia therapy is a non-pharmacological intervention used by athletes and individuals with cardiovascular disease, amongst others. The safety and feasibility of (intermittent) hypoxia therapy and its short-term effects on Parkinson's disease (PD) symptoms were assessed in a previous exploratory phase I trial. However, the net effects of multiple hypoxia treatment sessions on PD symptoms are unknown. The results of the previous phase I trial informed the study design of the newly proposed phase 1b-2a safety and efficacy trial. 45 minutes of normobaric intermittent hypoxia (FiO2 0.16 for 5 minutes interspersed with 5 minutes normoxia) will be delivered via a hypoxicator (a device that titrates decreased fractional oxygen from room air) through an oxygen mask in the hospital and subsequently at participants' homes. Interventions will be conducted 3 times a week, for 4 weeks in total.

Official Title
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A Randomized Phase 1b-2a Trial of the Safety and Effectiveness of Intermittent Hypoxia Treatment in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Other: Hypoxia through modified hypoxic generator
* Other: Normoxia through hypoxic generator without active elements


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Informed consent Clinical diagnosis of Parkinson's disease by a movement disorder specialized neurologist. Hoehn and Yahr staging 1 to and including 3 (indicating mild to moderate PD). Exclusion criteria A potential subject who meets any of the following criteria will be excluded from participation in this study: Individuals with diseases leading to restrictive and obstructive pulmonary diseases, sleep apnea and cardiac output deficits, such as pulmonary fibrosis, COPD, sleep apnea or excessive alcoholic intake, and congestive heart failure respectively Individuals with coronary artery disease NYHA classes III and IV Arterial blood gas abnormalities at screening procedure Individuals with shortness of breath or other airway or breathing-related inconvenience related to lack of dopaminergic medication Inability for in-clinic measurements in OFF phase Individuals with active deep brain stimulation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Hypoxic generator without active elements, pulsewise ventilation assured to ascertain blinding | Other: Normoxia through hypoxic generator without active elements<br>* Commercially available hypoxic generator, modified to allow for convenient remote interventions by non-expert participants, without active elements.<br>|
| Experimental: Active intervention<br>FiO2 0.16 for 5 minutes interspersed with 5 minutes normoxia (intermittent hypoxia) | Other: Hypoxia through modified hypoxic generator<br>* Commercially available hypoxic generator, modified to allow for convenient remote interventions by non-expert participants.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and nature of adverse events |  | 2 months | 
| Feasibility questionnaire, overall study success | Higher indicates better score | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDS-UPDRS part II and III | Lower indicates better score | 1 month | 
| Purdue pegboard test (PPT) | Higher indicates better score | 1 month | 
| Timed up & Go Test (TUGT) | Lower indicates better score | 1 month | 
| Exercise tolerance (6-minute walk test, 6MWT) | Higher indicates better score | 1 month | 
| Accelerometry data for tremor amplitude | Lower indicates better score | 1 month | 
| Accelerometry data for pronation-supination | Higher indicates better score | 1 month | 
| Hematocrit | Higher indicates better result | 1 month | 
| Neurofilament light chain (NfL) | Higher indicates better result | 1 month | 
| BDNF | Higher indicates better result | 1 month | 
| Platelet-derived growth factor receptor beta (PDGFRβ) | Higher indicates better result | 1 month | 
| Clusterin | Higher indicates better result | 1 month | 
| GFAP | Higher indicates better result | 1 month | 
| UCH-L1 | Higher indicates better result | 1 month |