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 feasibility study, 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 intermittent hypoxia intervention. 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, including the 9-Hole Peg Test of the dominant hand Timed 25-Foot Walk Test and the Symbol Digit Modalities Test. These findings indicate that a 12-week intermittent hypoxia intervention is safe and feasible in pwMS and support further investigation of its potential neuroprotective effects in larger, controlled trials.

间歇性低氧干预或许可为多发性硬化（multiple sclerosis, MS）患者（pwMS，people with multiple sclerosis）提供一种增强神经保护作用的替代治疗方案。然而，目前尚缺乏针对该干预在pwMS患者中安全性与可行性的相关临床数据。本项前瞻性可行性研究从汉堡-埃彭多夫大学医学中心MS门诊招募了以原发进展型多发性硬化为主的受试者（年龄18~60岁；扩展残疾状态量表（Expanded Disability Status Scale, EDSS）评分≤6.5），并为其实施为期12周的间歇性低氧干预。受试者每周完成2~3次标准化2小时疗程，模拟海拔最高可达4500米，对应最低吸入氧分数（fraction of inspired oxygen, FiO2）为11%。本研究的主要结局为急性高原病的发生情况，采用路易斯湖评分（Lake Louise Score, LLS）进行评估。次要结局指标包括系统不良事件、干预依从性、残疾评估指标、患者报告结局、神经心理学筛查结果、磁共振成像（magnetic resonance imaging, MRI）所示疾病活动度、外周血免疫细胞亚群、血清神经丝轻链（neurofilament light chain, NfL）水平及血清代谢组学特征。本研究共纳入12例pwMS患者，其中10例完成了全部干预流程。干预期间无受试者出现中重度高原病症状，亦未观察到系统性安全相关问题，或临床、影像学及实验室参数出现恶化。探索性分析结果显示，与残疾相关的结局指标有所改善，包括利手九孔柱测试（9-Hole Peg Test, 9HPT）、计时25英尺步行测试（Timed 25-Foot Walk Test, T25FW）以及符号数字模态测试（Symbol Digit Modalities Test, SDMT）。上述结果表明，12周间歇性低氧干预在pwMS患者中具备安全性与可行性，同时支持开展更大规模的对照试验以进一步探究其潜在神经保护作用。