Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson's disease: study rationale and protocol.
Clinical trial
Disease-modifying
Hypoxia
Mitochondrial dysfunction
Parkinson’s disease
Treatment
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
14 Jul 2022
14 Jul 2022
Historique:
received:
23
05
2022
accepted:
24
06
2022
entrez:
14
7
2022
pubmed:
15
7
2022
medline:
19
7
2022
Statut:
epublish
Résumé
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 short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson's Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis. This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).
Sections du résumé
BACKGROUND
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 short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD.
METHODS/DESIGN
METHODS
In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson's Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis.
DISCUSSION
CONCLUSIONS
This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).
Identifiants
pubmed: 35836147
doi: 10.1186/s12883-022-02770-7
pii: 10.1186/s12883-022-02770-7
pmc: PMC9281145
doi:
Banques de données
ClinicalTrials.gov
['NCT05214287']
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
262Subventions
Organisme : Michael J. Fox Foundation for Parkinson's Research
ID : 019201
Organisme : Michael J. Fox Foundation for Parkinson's Research
ID : 019201
Organisme : Michael J. Fox Foundation for Parkinson's Research
ID : 019201
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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