Objective: In this study, we describe the safety and short-term effects of the first hypoxia-based treatment trial in Parkinson’s disease by deploying a personalized multiple N-of-1 approach.

Background: Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have symptomatic and neuroprotective properties. Here, we present the results of the very first study that assesses the safety and physiological and symptomatic response to moderate hypoxia in PD.

Method: In 200 interventions divided over 20 randomized double-blinded N-of-1 studies, four different 45-minute hypoxia conditions were compared to placebo. All interventions were administered twice and consisted of intermittent hypoxia or continuous hypoxia at FiO2 0.163 or FiO2 0.127. Safety was measured by the number and nature of adverse events and physiological responses. Feasibility was evaluated using a questionnaire. Secondary outcomes included Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test (TUGT), Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Self-reported symptom scales included measurements of subjective motor and non-motor symptoms on a 10-point Likert scale. As part of a hypothesis-generating part of the study, erythropoietin, platelet-derived growth factor receptor β and cortisol were included. Secondary outcomes were analyzed using both Bayesian and frequentist analysis.

Results: 20 individuals with PD with a range of Hoehn & Yahr scores 1.5–3 were included. Number and nature of adverse events, MDS-UPDRS part III, TUGT, MiniBES and wrist accelerometry for the different hypoxia interventions were compared to placebo. Analysis is currently ongoing.

Conclusion: In this first experimental study, we have administered moderate hypoxia in a controlled setting in individuals with PD. By evaluating symptomatic and physiological responses, we provide insight in whether the hypoxia response pathway could be deployed as a novel potential disease-modifying target in PD, either by direct hypoxia administration or by activating the hypoxia response pathway by small molecules. This trial also demonstrates the feasibility of N-of-1 designs in PD and of including individualized outcomes in PD, as a basis for personalized treatment approaches.

References: 1. Janssen Daalen, J.M., Meinders, M.J., Giardina, F. .., B.R. Bloem. Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson’s disease: study rationale and protocol. BMC Neurol 22, 262 (2022). https://doi.org/10.1186/s12883-022-02770-7
2. Janssen Daalen, J.M., Meinders M.J., D.H.J. Thijssen, B.R. Bloem (2022). ClinialTrials.Gov. Identifier: NCT05214287.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multiple-n-of-1-trials-to-investigate-hypoxia-based-treatment-in-parkinsons-disease-safety-and-short-term-effects/