Twelve-week intermittent hypoxia intervention in multiple sclerosis - A safety and feasibility trial.

Intermittent hypoxia intervention may provide an alternative therapeutic approach to enhance neuroprotection in people with multiple sclerosis (pwMS). However, clinical data on its safety and feasibility in pwMS are lacking. In this prospective single-arm safety and feasibility trial, individuals with primarily progressive MS (18-60 years; Expanded Disability Status Scale ≤6.5) were recruited from the MS outpatient clinic of the University Medical Center Hamburg-Eppendorf and underwent a 12-week repetitive continuous hypoxia (RCH). Participants completed two to three standardized 2-hour sessions per week simulating altitudes of up to 4,500 meters, corresponding to a minimum fraction of inspired oxygen of 11%. The primary outcome was the occurrence of acute high-altitude sickness, assessed using the Lake Louise Score (LLS). Secondary outcomes included systemic adverse events, adherence, disability measures, patient-reported outcomes, neuropsychological screening tests, MRI disease activity, immune cell subpopulations in peripheral blood, serum neurofilament light chain levels, and serum metabolomic profiles. Twelve pwMS were enrolled, and ten completed the intervention. No participant developed moderate or severe symptoms of high-altitude illness, and no systemic safety concerns or worsening of clinical, radiological, or laboratory parameters were observed over the intervention period. Exploratory analyses suggested improvements in disability-related outcomes. These findings indicate that a 12-week RCH is safe and feasible in pwMS and support further investigation in larger, controlled trials.