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

NCT06121206 | Completed

• 2 other identifiers: H-22028111P-2022-354
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Cognitive Impairment; Bipolar Disorder; Depression

Keywords

Cognition; Neuroplasticity; Hypoxia; Cognitive training; Depression; Bipolar Disorder; Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Cognitive composite score

  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.

  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)

Secondary Outcomes (3)

• "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)

Other Outcomes (20)

• Rey Auditory Verbal Learning Test

  Baseline, week 4 (end of treatment), and week 8 (+end of treatment follow-up for patients in treatment as usual group)

• Trail Making Test Part A

  Baseline, week 4 (end of treatment), and week 8 (+end of treatment follow-up for patients in treatment as usual group)

• Trail Making Test Part B

  Baseline, week 4 (end of treatment), and week 8 (+end of treatment follow-up for patients in treatment as usual group)

Study Arms (5)

Altitude-like hypoxia (12%) combined with cognitive training

EXPERIMENTAL

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.

Other: Altitude-like hypoxia (12% O2); Behavioral: Cognitive training

Altitude-like hypoxia (12%) with no training

ACTIVE COMPARATOR

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.

Other: Altitude-like hypoxia (12% O2); Behavioral: Sham training

Normoxia (20%) combined with cognitive training

ACTIVE COMPARATOR

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.

Other: Normoxia (20% O2); Behavioral: Cognitive training

Normoxia (20%) combined with no training

SHAM COMPARATOR

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.

Other: Normoxia (20% O2); Behavioral: Sham training

Treatment as usual

NO INTERVENTION

Participants receive no additional care or intervention between baseline and end-of-treatment assessment points.

Interventions

Altitude-like hypoxia (12% O2) OTHER

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

Altitude-like hypoxia (12%) combined with cognitive training; Altitude-like hypoxia (12%) with no training

Normoxia (20% O2) OTHER

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

Normoxia (20%) combined with cognitive training; Normoxia (20%) combined with no training

Cognitive training BEHAVIORAL

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).

Altitude-like hypoxia (12%) combined with cognitive training; Normoxia (20%) combined with cognitive training

Sham training BEHAVIORAL

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.

Altitude-like hypoxia (12%) with no training; Normoxia (20%) combined with no training

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years
• No psychiatric history
• Fluency in Danish
• 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 ≥14.

You may not qualify if:

• Schizophrenia or schizoaffective disorder
• Neurological disorder
• Alcohol or substance abuse
• History of serious head trauma
• Previous altitude sickness
• Heart disease
• Diabetes
• 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
• BMI\>30

Sponsors & Collaborators

• Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital: lead
• European Research Council: collaborator
• University of Copenhagen: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Neurocognition and Emotion in Affective Disorders (NEAD) Centre, University of Copenhagen and Psychiatric Centre Copenhagen, Frederiksberg hospital

Copenhagen, Capital Region of Copenhagen, 1353, Denmark

Location

Related Publications (1)

• Miskowiak KW, Damgaard V, Schandorff JM, Macoveanu J, Knudsen GM, Johansen A, Plaven-Sigray P, Svarer C, Fussing CB, Cramer K, Jorgensen MB, Kessing LV, Ehrenreich H. Effects of cognitive training under hypoxia on cognitive proficiency and neuroplasticity in remitted patients with mood disorders and healthy individuals: ALTIBRAIN study protocol for a randomized controlled trial. Trials. 2024 Oct 3;25(1):648. doi: 10.1186/s13063-024-08463-5.

  PMID: 39363230 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Bipolar Disorder; Depression; Hypoxia

Interventions

Cognitive Training

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders; Behavioral Symptoms; Behavior; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Kamilla W Miskowiak, DMSc, DPhil

  Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 31, 2023
• First Posted: November 7, 2023
• Study Start: February 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: July 30, 2025
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)