Supramaximal High-Intensity Interval Training in People With and Without Chronic Obstructive Pulmonary Disease

NCT06068322 | Recruiting DMC

• 4 other identifiers: COPD-HIIT RCT2020-012962020-0139101078602
• Study Type: interventional
• Target: 208
• Locations: 2 countries
• Sites: 2

Brief Summary

Beyond pulmonary complications, COPD presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods. The COPD-HIIT trial intend to investigate the effects and mechanisms of 12 weeks supramaximal high-intensity interval-training (HIIT) compared to moderate intensive continous training (MICT) in people with COPD and matched healthy controls on important clinical outcomes. The trial also intends to compare the effects of 24 months of exercise training (supramaximal HIIT or MICT) to usual care in people with COPD on brain health, cardiorespiratory fitness and muscle power; in people with COPD.

Conditions

COPD; Healthy Controls

Keywords

Chronic obstructive Pulmonary Disease; Pulmonary Disease, Chronic Obstructive; Chronic airway disease; COPD; physical activity; exercise

Outcome Measures

Primary Outcomes (3)

• Change from baseline global cognitive function

  Global cognitive function will be assessed as the Z-score determined by the combined performances on six tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the trail making test (TMT-A, TMT-B). The following tests from the CANTAB will be used: Motor screening task, reaction time, visual information processing, paired associates learning, spatial working memory, verbal recognition memory. The test battery takes around 60 minutes to complete. The test scores from the seven tests will be combined into a composite Z-score. The Z-score describes how much a point deviates from a mean or specific point. The Z-score represents how many standard deviations an individual's score is from the mean score of the reference population, which is represented as zero.

  Baseline, 12 weeks, 24 months

• Change from baseline cardiorespiratory fitness

  Measured as maximum oxygen uptake (VO2peak \[ml O2/min/kg\]) during a standardized ramp-protocol cardiopulmonary exercise test (CPET) on a cycle ergometer. The CPET will start with a 3-minute resting phase before a 3-minute unloaded (or lowest wattage possible) warm-up phase. The aim is to have a ramp-phase of 8-12 minutes, until the participant stops due to voluntarily exhaustion, symptom-limitation or failure to maintain a cadence of 50-70 RPM.

  Baseline, 12 weeks, 24 months

• Change from baseline quadriceps muscle power

  Peak power (Nm/s) assessed during a seated leg extension in a dymanometer (Biodex System 4). Participants will be instructed to extend their leg as fast and as hard as possible and then passively return the leg to the starting position.

  Baseline, 12 weeks, 24 months

Secondary Outcomes (64)

• Change from baseline brain structure

  Baseline, 12 weeks, 24 months

• Change from baseline brain activity

  Baseline, 12 weeks, 24 months

• Change from baseline cerebral perfusion

  Baseline, 12 weeks, 24 months

• Change from baseline neuroinflammation

  Baseline, 12 weeks, 24 months

• Change from baseline exercise tolerance

  Baseline, 12 weeks, 24 months

Other Outcomes (14)

• Baseline global cognitive function

  Baseline

• Baseline cardiorespiratory fitness

  Baseline

• Baseline muscle power

  Baseline

Study Arms (3)

Supramaximal high-intensity interval training (Supramaximal HIIT)

EXPERIMENTAL

Each HIIT session consists of 10 repeated 6-seconds regulated high intensity cycling sprints against an individualized load set to reach a supramaximal exercise intensity (i.e. power output is higher than power output at maximum oxygen uptake). Session duration for HIIT is initially 20 min, including warm-up (5 min) and cool-down (5 min). The protocol enables controlled and systematic adjustments of training intensity by means of standardized criteria.

Other: Exercise training on a stationary bicycle

Moderate-intensity continuous training (MICT)

ACTIVE COMPARATOR

Each MICT session will consist of aerobic training regulated against an individualized load set to reach a moderate submaximal exercise intensity (i.e. power output is lower than power output at maximum oxygen uptake). Session duration for MICT is initially 30 min, including warm-up (5 min) and cool-down (5 min). The protocol enables controlled and systematic adjustments of training intensity by means of standardized criteria.

Other: Exercise training on a stationary bicycle

Usual care

NO INTERVENTION

The passive control group will receive usual care alone and a standardized phone call every three months including assessments of health status (CAT), disease specific quality of life (CRQ) and questions on symptoms of exacerbations. We will match the participants in the standard care group to those randomized to HIIT or MICT by age, sex, disease severity, educational level, and physical activity.

Interventions

Exercise training on a stationary bicycle OTHER

Training is performed two to three times per week for a total of 30 sessions using a group format. Both regimens start with a five-minute warm-up and ends with a five-minute cool-down, performed at an intensity corresponding to 30% of the maximal work rate achieved during a CPET (i.e., max aerobic power \[MAP\]) with a self-selected pedalling cadence of 50-70 revolutions per minute (RPM). All exercise sessions will be held and supervised by an experienced health care professional, i.e. physiotherapists or other health professional. The different types of exercise training is described under the specific arm. Following the first 12-week training period, participants with COPD will enter a 21-month maintenance phase. They will continue to exercise using the same training modality (HIIT or MICT) as during the first 12-weeks but can select between three different settings to continue their training: "Home", "Outpatient", or "Mix" setting.

Moderate-intensity continuous training (MICT); Supramaximal high-intensity interval training (Supramaximal HIIT)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Independent in activities of daily living
• For people with COPD: Symptomatic (COPD assessment test \[CAT\] ≥10 or modified Medical Research Council dyspnea scale \[mMRC\] ≥2) or not being regularly physically active at a moderate or high intensity over the last year defined as not meeting WHO requirements for physical activity.
• For people with COPD: Post-bronchodilator spirometry confirmed COPD diagnosis (forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio \< 0.70).
• For healthy controls: Normal lung function

You may not qualify if:

• Movement related conditions, cardiovascular, neuromuscular, metabolic, skeletal and/or rheumatic conditions and diseases that are unstable and/or prohibits exercise or tests, based on screening by a physician. For example, but not limited to:
• I. Musculoskeletal pain prohibiting participation in tests and exercise II. Recent myocardial infarction, coronary artery bypass grafting, angioplasty, or other cardiac events III. Uncontrolled arterial hypertension IV. Pathological ECG-findings during CPET
• Other lung conditions, including, but not limited to asthma, interstitial lung disease, lung cancer, pulmonary hypertension, pulmonary vascular disease, pulmonary fibrosis
• Medical conditions and treatments with known effects on brain function and cognition, for example:
• I. Previous trauma to the head with lasting cognitive or symptom-related issues II. Physical or mental disabilities III. Neurological condition (dementia, multiple sclerosis, stroke) IV. Psychiatric illness, not including depression or general anxiety disorder V. Severe cognitive impairment VI. Recent or current cancer diagnosis and treatment
• For those accepting MRI or PET/CT: metal implants, pacemakers, claustrophobia and other MRI incompatible factors.
• Inability to read or speak Swedish (Umeå participants), Dutch, French (Hasselt participants) or English (Umeå and Hasselt participants).
• For people with COPD:
• I. Co-morbid conditions that limit exercise performance to a greater extent than the COPD diagnosis.
• II. Currently participating in a pulmonary rehabilitation program or have been involved in pulmonary rehabilitation in the last 12 months.
• III. Experienced a COPD exacerbation that led to a change in medication dosage or frequency in the preceding six weeks.

Sponsors & Collaborators

• Umeå University: lead
• Hasselt University: collaborator
• Swedish Heart Lung Foundation: collaborator
• European Research Council: collaborator
• The Swedish Research Council: collaborator
• Ziekenhuis Oost-Limburg: collaborator
• Strategic Research Area - Health Care Science: collaborator

Study Sites (2)

Hasselt University

Hasselt, Diepenbeek, 3590, Belgium

RECRUITING

Umeå University

Umeå, Sweden

RECRUITING

Related Publications (1)

• Jakobsson J, Burtin C, Hedlund M, Boraxbekk CJ, Westman J, Karalija N, Stal P, Sandstrom T, Ruttens D, Gosker HR, De Brandt J, Nyberg A. Effects and mechanisms of supramaximal high-intensity interval training on extrapulmonary manifestations in people with and without chronic obstructive pulmonary disease (COPD-HIIT): study protocol for a multi-centre, randomized controlled trial. Trials. 2024 Oct 8;25(1):664. doi: 10.1186/s13063-024-08481-3.

  PMID: 39375781 DERIVED

Related Links

• Study site at Umeå University

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Motor Activity

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• André Nyberg, PhD

  Umeå University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

André Nyberg, PhD

CONTACT

+46 090-786 66 39; andre.nyberg@umu.se

Johan Jakobsson, M.Sc.

CONTACT

+46 090 786 63 73; johan.jakobsson@umu.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The outcome assessors and data analysts will be masked to group allocation. The participants will be given repeated instructions not to reveal their group allocation to the outcome assessors. The dataset will be blinded regarding group allocation when performing analyses.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In Phase 1, participants will be randomised to either interventional arm or control arm with a 1:1 allocation ratio, using a computer-generated block randomisation schedule stratified for sex (male, female), age and centre with equal allocation to all study arms. For Phase 2 only the participants with COPD will continue the maintenance program in their allocated group. A usual of care group consisting of patients with COPD will also be recruited to serve as control in the maintenance part.

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: October 5, 2023
• Study Start: November 9, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will become available 6 months after publication. The full study protocol including the analysis plan will be submitted for publication during 2023. Informed consent forms and other supporting material will be available on a reasonable request to the principal investigator.
• Access Criteria: The principal investigator will review requests for supporting material. IPD will be open access in a data repository.

Locations

SE (1); BE (1)