{"doi":"10.1161/strokeaha.124.047261","title":"Acute Intermittent Hypoxia With High-Intensity Gait Training in Chronic Stroke: A Phase II Randomized Crossover Trial","abstract":"BACKGROUND: Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke. METHODS: This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds <1.0 m/s. Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60–90 seconds; 8%–9% O 2 ) and normoxia (30–60 seconds; 21% O 2 ), followed by 1 hour of HIT targeting >75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions. RESULTS: Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08–0.18] versus 0.05 [0.01–0.10] m/s), fastest speed (0.16 [0.10–0.21] versus 0.06 [0.02–0.10] m/s), and peak treadmill speed (0.21 [0.14–0.29] versus 0.11 [0.06–0.16] m/s) following AIH+HIT versus normoxia+HIT ( P <0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT, with worse outcomes for those prescribed serotonin-mediated antidepressant medications. CONCLUSIONS: AIH+HIT resulted in greater gains in locomotor function than normoxia+HIT. Subsequent phase III trials should further evaluate the efficacy of this intervention. REGISTRATION: URL: https://clinicaltrials.gov/ ; Unique identifier: NCT04472442.","journal":"Stroke","year":2024,"id":438513,"datarank":0.5318676030472724,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.1721833121275168,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.1721833121275168,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":10,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04472442"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":878159,"name":"Abbey Plawecki","orcid":null,"position":1,"is_corresponding":false},{"id":265130,"name":"Jennifer Lotter","orcid":null,"position":2,"is_corresponding":false},{"id":1249191,"name":"Lindsay H. Shoger","orcid":null,"position":3,"is_corresponding":false},{"id":1249192,"name":"Christina Voigtmann","orcid":null,"position":4,"is_corresponding":false},{"id":1249193,"name":"Erin Inks","orcid":null,"position":5,"is_corresponding":false},{"id":503561,"name":"Christopher E. Henderson","orcid":"0000-0002-9464-2789","position":6,"is_corresponding":false},{"id":495859,"name":"T. George Hornby","orcid":"0000-0002-3147-3818","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:00:43.618468Z","pmid":"38860389","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}