Background
Study objectives
Primary objectives
Secondary objectives
Hypothesis
Methods/Design
Multiple N-of-1 trials
Study population
Inclusion criteria | Exclusion criteria |
---|---|
Clinical diagnosis of Parkinson’s disease by a movement-disorder specialized neurologist | Individuals with diseases leading to restrictive and obstructive pulmonary diseases, pulmonary diffusion deficits, apnea and cardiac output deficits, such as pulmonary fibrosis, COPD, sleep apnea or excessive alcoholic intake, and congestive heart failure respectively |
Hoehn and Yahr staging 1.5 to 3 | Arterial blood gas abnormalities at screening day |
Age > 18 years | Individuals with shortness of breath or other airway or breathing-related inconvenience related to lack of dopaminergic medication will be excluded |
Participant can provide informed consent | Inability to comply to intervention in off-medication condition (for example due to extreme discomfort, distress or severe head tremor due to being OFF, i.e. without dopaminergic medication) |
Individuals with unstable dopaminergic medication dose (changes in the last month) | |
Individuals likely to start dopaminergic treatment in the next month, also judged by their treating neurologist | |
Individuals with active deep brain stimulation | |
Individuals unable to provide informed consent |
Sample size
Recruitment, screening and inclusion
Intervention
-
Continuous hypoxia for 45 min, at ~ 2000 m (16.3% O2)
-
Continuous hypoxia for 45 min, at ~ 4000 m (12.7% O2)
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Intermittent hypoxia with 5 × 5-min at ~ 2000 m (16.3% O2), interspersed with 5-min normoxic recovery
-
Intermittent hypoxia with 5 × 5-min at ~ 4000 m (12.7% O2), interspersed with 5-min normoxic recoveryPlacebo intervention:
-
Continuous normoxia for 45 min (20.9% O2)
Study procedures
Screening
Pilot phase
Intervention
Randomization and blinding
Randomization
Blinding
Outcomes and measurements
Primary outcomes
Primary outcome variable | Measurement frequency |
---|---|
Nature and number of adverse events | Every 10 min during intervention, up to one hour post-intervention, one time next morning post-intervention |
Self-reported dizziness, discomfort and stress on a ten-point scale | Every 10 min up to one hour post-intervention, one time next morning post-intervention |
Number of serious or irreversible adverse events | Every 10 min, up to one hour post-intervention, one time next morning post-intervention |
Measured continuously for safety, recorded: | |
- Blood pressure systolic-diastolic | Baseline and every 5 min—> 30 min post-intervention |
- Heartrate | Baseline and every 5 min—> 30 min post-intervention |
- Respiratory rate | Baseline and every 5 min—> 30 min post-intervention |
- Oxygen saturation | Baseline and every 5 min—> 30 min post-intervention |
Feasibility questionnaire (total score and subscores) (in Supplementary Materials) | After 1st, 5th and 10th intervention |
Secondary outcomes
Self-reported outcomes
Self-reported outcome variable | Researcher | Participant | Moment of measurement (in addition to baseline) | Measurement unit |
---|---|---|---|---|
General symptom impression | X | Directly after intervention and post-intervention 30 min, 1 h, 2 h, 3 h, 4 h and 5 h, and once every morning on the next three days | 10-point Likert scale allowing half points | |
Urge for dopaminergic medication on the usual moments of intake | X | Directly after intervention and post-intervention 30 min, 1 h, 2 h, 3 h, 4 h and 5 h, and once every morning on the next three days | 10-point Likert scale allowing half points | |
Participant-selected symptom (goal attainment scale) | X | Directly after intervention and post-intervention 30 min, 1 h, 2 h, 3 h, 4 h and 5 h, and once every morning on the next three days | 10-point Likert scale allowing half points | |
Motor symptom severity (self-selected, symptom that improved most during high altitude exposure, if applicable) | X | Directly after intervention and post-intervention 30 min, 1 h, 2 h, 3 h, 4 h and 5 h, and once every morning on the next three days | 10-point Likert scale allowing half points | |
Motor symptoms MDS-UPDRS part III | X | 30 min post-intervention | Total score and subscores | |
Hand tremor Accelerometry/gyroscope | X | Directly post-intervention, 30 min post-intervention | Amplitude | |
Rapid alternating movements Accelerometry/gyroscope | X | 30 min post-intervention | Amplitude | |
Bradykinesia Modified Perdue pegboard test | X | 30 min post-intervention | Number of pins | |
Gait Timed Up & Go Test | X | 30 min post-intervention | Steps and seconds | |
Balance MiniBESTest | X | 30 min post-intervention | Total score and subscores | |
Non-motor symptoms MDS Non-motor Scale symptoms | X | 30 min post-intervention | 10-point Likert scale (half points) | |
Stress Heartrate variability | X | During intervention, directly after intervention, 30 min post-intervention | RR interval |