NCT06121206

Effects of Altitude-like Cognition Training on Neuroplasticity and Cognitive Functions

Altitude-like Cognition Training to Target Brain Erythropoietin as a Novel Mechanism of Long-lasting Neuroplasticity and Cognitive Functions

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 190 (actual)
• Sponsor: Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

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).

Detailed description

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.

Conditions

• Cognitive Impairment
• Bipolar Disorder
• Depression

Interventions

Type	Name	Description
OTHER	Altitude-like hypoxia (12% O2)	Fresh air with 12% O2, is blown into a sealed 20 m³ room by a 4kW air compressor with a safety-approved system developed by HöhenBalance, Austria. After participants enter the room, the O2 levels will be reduced from 16% to 12% (≈ 4,400 meters altitude) in a 30 minutes lead-in phase. The target O2 level of 12% will be maintained over three hours
OTHER	Normoxia (20% O2)	Fresh air with 20% O2, is blown into a sealed 20 m³ room by a 4kW air compressor with a safety-approved system developed by HöhenBalance, Austria. The target O2 level of 20% will be maintained over 3.5 hours
BEHAVIORAL	Cognitive training	The web-based cognitive training (Happy Neuron Pro) is grounded on principles of neuroplasticity-based learning by being intensive, neuroadaptive, engaging and rewarding. The active training involves parametric task adjustment by decreasing stimuli presentation time, increasing working memory load, decreasing time to respond, and increasing the number of non-target items (distractors).
BEHAVIORAL	Sham training	Participants in the no training control condition receive computer games similar to Happy Neuron Pro but with low cognitive demand that produce no cognitive benefits. Specifically, this sham procedure involves the exact same stimuli as the active condition but with changes from trial to trial only in the appearance of the tasks.

Timeline

• Start date: 2023-02-01
• Primary completion: 2025-07-01
• Completion: 2025-07-30
• First posted: 2023-11-07
• Last updated: 2025-09-26

Locations

1 site across 1 country: Denmark