Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial
Rattachement africain : br, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Background Respiratory impairment is a major concern in amyotrophic lateral sclerosis (ALS), shortening survival and lowering quality of life. One therapy with promise to delay respiratory decline in ALS is acute intermittent hypoxia (AIH), consisting of alternating periods of breathing mildly hypoxic (9%-12% O2) and normoxic (21% O2) gas. AIH stimulates spinal, serotonin-dependent neuroplasticity in rodent models, conferring functional benefits in diverse physiological systems without detectable pathology. However, in rodent models, AIH-induced neuroplasticity is constrained by distinct signaling cascades initiated by spinal adenosine. Objective We propose to investigate a therapeutic strategy to delay breathing compromise in those living with ALS by combining a selective adenosine 2A (A2A) receptor inhibitor (istradefylline) with AIH. The fundamental hypothesis guiding this proposal is that a single AIH trial after pretreatment with istradefylline enhances respiratory neuroplasticity versus AIH or sham intervention. Methods We propose to evaluate resting breathing, respiratory strength, and participant-reported symptoms in adults living with ALS after combined istradefylline plus AIH. A mixed within- and between-participant study design incorporates 4 test sessions, separated by approximately 2 weeks (±5 days). Testing conditions include single sessions of AIH + istradefylline, AIH + placebo, sham AIH (ie, normoxia) + placebo, and sham AIH + istradefylline. Safety and feasibility will be characterized using the rate of adverse events, changes in vital signs, and participant-reported breathing sensations (Aim 1). Neuroplasticity of breathing and motor function will be evaluated as changes in resting breathing, voluntary respiratory strength, respiratory control, and maximal pinch force (Aim 2). Results As of January 2025, with a target sample of 16 participants in each group, 10 participants with ALS and 5 control participants completed study procedures. Recruiting is ongoing, and the final participant will complete the study by December 2025. Publication of results is expected by the end of 2026. Conclusions These aims will provide crucial data regarding the preliminary safety and feasibility of this paired intervention and help optimize therapeutic AIH as a rehabilitation strategy, thereby guiding further research concerning this novel treatment for ALS. Trial Registration ClinicalTrials.gov NCT05377424; https://clinicaltrials.gov/study/NCT05377424 International Registered Report Identifier (IRRID) DERR1-10.2196/76105
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial
- Date Crossref
- 07/11/2025
- Éditeur
- JMIR Publications Inc.
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Universidade do Estado de Santa Catarina Department of Physical Therapy pays non établi dans la noticeUniversité ou école supérieure
-
University of Florida Health Breathing Research and Therapeutics Center pays non établi dans la noticeUniversité ou école supérieure
-
University of Florida pays non établi dans la noticeUniversité ou école supérieure
-
University of Florida Health Science Center pays non établi dans la noticeUniversité ou école supérieure
-
Florida College pays non établi dans la noticeUniversité ou école supérieure
-
Appalachian State University pays non établi dans la noticeUniversité ou école supérieure
-
Jacksonville University pays non établi dans la noticeUniversité ou école supérieure
-
College of Public Health and Health Professions pays non établi dans la noticeUniversité ou école supérieure
-
Beaver College of Health Sciences pays non établi dans la noticeUniversité ou école supérieure
-
College of Engineering pays non établi dans la noticeUniversité ou école supérieure
-
College of Medicine pays non établi dans la noticeUniversité ou école supérieure
Department of Physical Therapy — Universidade do Estado de Santa Catarina, Breathing Research and Therapeutics Center — University of Florida Health et University of Florida, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.