Hypoxic conditioning in Parkinson's disease: randomized controlled multiple N-of-1 trials

Area of Science:

• Neurology
• Exercise Physiology
• Clinical Trials

Background:

• Preclinical studies suggest hypoxic conditioning benefits Parkinson's disease (PD) symptoms and offers neuroprotection.
• Investigating hypoxic conditioning's safety and efficacy in PD is crucial for potential therapeutic applications.
• Current understanding of hypoxic conditioning's effects on PD symptoms and biomarkers is limited.

Purpose of the Study:

• To assess the safety and feasibility of various hypoxic conditioning protocols in individuals with PD.
• To evaluate the short-term symptomatic effects of hypoxic conditioning on PD.
• To explore downstream effects and potential biomarkers related to hypoxic conditioning in PD.

Main Methods:

• 20 individuals with PD (Hoehn-Yahr 1.5-3) participated in a randomized, double-blinded, placebo-controlled N-of-1 trial.
• Participants underwent five 45-minute hypoxia interventions (continuous and intermittent at FiO2 0.163 and 0.127) and a placebo intervention, in duplicate.
• Safety, feasibility, symptom scores (participant and assessor-rated), and exploratory serum biomarkers (EPO, BDNF, GFAP, NfL, PDGFRβ, cortisol) were measured.

Main Results:

• The study met primary endpoints for safety and feasibility, with hypoxic conditioning being well-tolerated.
• 95 adverse events occurred, with no dose-dependency and similar incidence between hypoxia and placebo; two participants experienced significant oxygen desaturations.
• Intermittent hypoxia at FiO2 0.163 showed modest, short-term improvements in participant-rated symptoms compared to placebo, but not assessor-rated scales; serum biomarkers did not differ significantly.

Conclusions:

• Hypoxic conditioning is a safe and feasible intervention for individuals with Parkinson's disease.
• Specific protocols, like intermittent hypoxia at FiO2 0.163, may offer temporary symptomatic relief.
• Findings support further investigation into the long-term safety and efficacy of hypoxic conditioning for PD management.