Altitude-like Cognition Training to Target Brain Erythropoietin as a Novel Mechanism of Long-lasting Neuroplasticity and Cognitive Functions
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 190
- 试验地点
- 2
- 主要终点
- Cognitive composite score
研究概览
简要总结
The goal of this clinical trial is to investigate the effects of a three-week altitude-like cognition training intervention in healthy individuals (substudy 1) and symptomatically stable patients with mood disorders (depression or bipolar disorder; substudy 2). This multi-modal intervention consists of an adaptive cognitive training programme that participants complete while they're inside an altitude-training room with 12% O2, corresponding to 4400 meters altitude.
Across substudy 1 and 2, the investigators hypothesize that altitude-like cognition training has a beneficial effect on cognition after three-weeks treatment completion measured with a global cognition composite score (primary outcome measure). Further, the investigators hypothesize that hypoxia and cognition training will yield improved executive functioning after treatment completion and changes in brain activity during working memory in the dorsal prefrontal cortex 4 weeks after treatment completion (secondary outcome measures). In the patient study, the investigators further hypothesize that the intervention will have beneficial effects on daily-life cognition measured in virtual reality (VR) 4 weeks after treatment completion (secondary outcome measure in substudy 2). For exploratory purposes, the study will examine effects on additional measures of cognition, functioning and self-ratings scales (tertiary outcomes).
The investigators will compare the combination of altitude-like hypoxia (12%) and cognitive training with (1) hypoxia with no training, (2) cognitive training under normal oxygen levels (normoxia; 20%), and (3) normoxia with no training in healthy individuals (substudy 1). For patients with mood disorders (substudy 2) the effects of altitude-like hypoxia (12%) and cognitive training are compared to treatment as usual (TAU).
详细描述
ALTIBRAIN aims to test a novel model, linking altitude-like oxygen manipulations, endogenous erythropoietin (EPO) in the brain, neuroplasticity and cognition. Specifically, ALTIBRAIN will determine whether upregulation of endogenous brain EPO by altitude-like hypoxia cognition training is a fundamental mechanism of enduring neuroplasticity and long-lasting cognitive improvement in humans. This will be investigated in healthy individuals (substudy 1) and symptomatically stable patients with mood disorders (depression or bipolar disorder; substudy 2).
Substudy 1 involves four intervention groups: (1) altitude-like hypoxia (12%) combined with cognitive training, (2) hypoxia with no training, (3) cognitive training under normoxia (20%), and (4) normoxia with no training. Participants are randomised in blocks of four and undergo interventions in these groups for practical reasons. During the 3-weeks treatment, participants breathe 12% ambient oxygen (≈4400 meters altitude) or normal sea-level oxygen (20%) in a treatment room, 3.5 hours daily, six days per week. On iPads, they perform cognitive training or matched control games without cognitive benefits. Cognitive training is interleaved by short breaks, during which the participants can relax or walk on a treadmill inside the room. Participants undergo cognition assessments in weeks 1 (baseline), 4 and 8 and functional and structural MRI in weeks 1 and 8, when red blood cells are comparable between groups. A subgroup will also undergo PET scanning in week 4.
In substudy 2, patients are randomized to either (1) altitude-like hypoxia (12%) combined with cognitive training, 3.5 hours daily, five-six days per week for three weeks or (2) treatment as usual (TAU). After completed testing, patients in the TAU group undergo the 3-week active intervention, followed by an additional session of neurocognitive testing in the week after treatment completion. All remaining study procedures are identical to substudy 1.
The power calculation was based on the primary hypothesis that altitude-like hypoxia combined with cognitive training produces robust sustained cognitive improvement compared with normoxia and no training. To accommodate for up to a 15% drop-out, we will include 30 participants per group; i.e., 120 healthy individuals and 60 patients to obtain complete data for minimum 26 participants per group, i.e., 104 healthy individuals and 52 patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Substudy 1: The study has a double-blinded design. Neither the participant nor the outcome assessors will know whether the participant is receiving (1) altitude-like hypoxia (12%) combined with cognitive training, (2) hypoxia with no training, (3) cognitive training under normoxia (20%), or (4) normoxia with no training.
Substudy 2: The study has an assessor-blinded design. The outcome assessor will not know whether the participant is receiving (1) altitude-like hypoxia (12%) combined with cognitive training or (2) treatment as usual (TAU).
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(substudy 1):
- •18-50 years
- •No psychiatric history
- •Fluency in Danish
- •Inclusion Criteria (substudy 2):
- •18-65 years
- •International Classification of Diseases (ICD)-10 diagnosis of Bipolar Disorder or depression confirmed with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN)
- •Fluency in Danish
- •Partial or full remission (defined as a score of ≤14 on the Hamilton Depression Rating Scale 17-items (HDRS-17) and the Young Mania Rating Scale (YMRS)
- •Objectively-verified cognitive impairment according to Screen for Cognitive Impairment in Psychiatry (SCIP) and/or self-reported cognitive impairment measured with Cognitive Complaints in Bipolar disorder Rating Assessment (COBRA). For SCIP, their performance must be ≥0.5 standard deviations (SD) below their demographically adjusted expected total SCIP score or on minimum 2 SCIP subtest scores. For COBRA, patients must report substantial cognitive impairment defined as a score ≥
排除标准
- •Schizophrenia or schizoaffective disorder
- •Neurological disorder
- •Alcohol or substance abuse
- •History of serious head trauma
- •Previous altitude sickness
- •Heart disease
- •Renal failure
- •Untreated/insufficiently treated hypertension
- •Thromboses or thromboembolic events
- •First-degree family with thromboembolic events before age 60
- •Pregnancy
- •Breastfeeding
- •Smoking or use other nicotine products regularly
- •Electroconvulsive therapy (ECT) 3 months prior to participation
- •Claustrophobia (MRI scans)
- •Pacemaker and/or other MRI incompatible metal implants (MRI scans)
- •Participation in experiments with radioactivity (>10 mSv) within the last year (PET scans)
- •Significant occupational exposure to radioactivity (PET scans)
- •Medication incompatible with study aims (e.g., SV2A binding agents; PET scans)
研究组 & 干预措施
Altitude-like hypoxia (12%) combined with cognitive training
Participants breathe 12% ambient oxygen in an altitude-training room, 3.5 hours daily, 5-6 days per week for 3 weeks. On iPads, they perform cognitive training, which is interleaved by short breaks.
干预措施: Altitude-like hypoxia (12% O2) (Other)
Altitude-like hypoxia (12%) combined with cognitive training
Participants breathe 12% ambient oxygen in an altitude-training room, 3.5 hours daily, 5-6 days per week for 3 weeks. On iPads, they perform cognitive training, which is interleaved by short breaks.
干预措施: Cognitive training (Behavioral)
Altitude-like hypoxia (12%) with no training
Participants breathe 12% ambient oxygen in an altitude-training room, 3.5 hours daily, 6 days per week for 3 weeks. On iPads, they perform matched control games without cognitive benefits, which is interleaved by short breaks.
干预措施: Altitude-like hypoxia (12% O2) (Other)
Altitude-like hypoxia (12%) with no training
Participants breathe 12% ambient oxygen in an altitude-training room, 3.5 hours daily, 6 days per week for 3 weeks. On iPads, they perform matched control games without cognitive benefits, which is interleaved by short breaks.
干预措施: Sham training (Behavioral)
Normoxia (20%) combined with cognitive training
Participants breathe 20% ambient oxygen in an altitude-training room, 3.5 hours daily, 6 days per week for 3 weeks. On iPads, they perform cognitive training, which is interleaved by short breaks.
干预措施: Normoxia (20% O2) (Other)
Normoxia (20%) combined with cognitive training
Participants breathe 20% ambient oxygen in an altitude-training room, 3.5 hours daily, 6 days per week for 3 weeks. On iPads, they perform cognitive training, which is interleaved by short breaks.
干预措施: Cognitive training (Behavioral)
Normoxia (20%) combined with no training
Participants breathe 20% ambient oxygen in an altitude-training room, 3.5 hours daily, 6 days per week for 3 weeks. On iPads, they perform matched control games without cognitive benefits, which is interleaved by short breaks.
干预措施: Normoxia (20% O2) (Other)
Normoxia (20%) combined with no training
Participants breathe 20% ambient oxygen in an altitude-training room, 3.5 hours daily, 6 days per week for 3 weeks. On iPads, they perform matched control games without cognitive benefits, which is interleaved by short breaks.
干预措施: Sham training (Behavioral)
Treatment as usual
Participants receive no additional care or intervention between baseline and end-of-treatment assessment points.
结局指标
主要结局
Cognitive composite score
时间窗: Baseline, week 4 (end of treatment. Primary outcome assessement time point), and week 8 (+end of treatment follow-up for patients in treatment as usual group)
A cognitive composite based on an average of Z-transformed scores from the Rey Auditory Verbal Learning Test (RAVLT), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding, verbal fluency with the letter "D", WAIS-III Letter-Number Sequencing, Trail Making Test B (TMT B) and Rapid Visual Information Processing (RVP) speed for correct responses from Cambridge Cognition (CANTAB). No score range. Higher scores mean a better outcome.
次要结局
- Dorsal prefrontal cortex activity during spatial N-back(Baseline, week 8)
- ONLY IN PATIENTS (SUBSTUDY 2): Cognition Assessement in Virtual Reality (CAVIR) test: Composite score(Baseline, week 8 (secondary outcome assessment time point) (+end of treatment follow-up for patients in treatment as usual group))
- "Mean choices to correct" in One Touch Stockings of Cambridge (OTS) from Cambridge Cognition (CANTAB)(Baseline, week 4 (end of treatment. Secondary outcome assessement time point), and week 8 (+end of treatment follow-up for patients in treatment as usual group))
- Dorsal prefrontal cortex activity during spatial N-back(Baseline, week 8)
- ONLY IN PATIENTS (SUBSTUDY 2): Cognition Assessement in Virtual Reality (CAVIR) test: Composite score(Baseline, week 8 (secondary outcome assessment time point) (+end of treatment follow-up for patients in treatment as usual group))
研究者
Kamilla Woznica Miskowiak
Professor
Mental Health Services in the Capital Region, Denmark