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

Abstract

Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (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 due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls.

Methods: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated.

Discussion: The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease.

Trial registration: Clinicaltrials.gov: NCT06068322. Prospectively registered on 2023-09-28.

Keywords: Aerobic exercise; Cognitive aspects; High-intensity interval training; Neurodegeneration; Pulmonary disease, Chronic obstructive; Randomized controlled trial; Skeletal muscle; Systemic inflammation.

Fig. 1

Visual representation of the COPD-HIIT trial. In phase 1 (RO1), supervised exercise training (supramaximal HIIT or MICT) will be performed two to three times per week for 12-weeks. In phase 2, participants with COPD will continue into a maintenance phase, exercising two times per week for 21-months. Legend: RO: research objective; HC: healthy controls; COPD: chronic obstructive pulmonary disease; HIIT, supramaximal high-intensity interval training, MICT, moderate intensity continuous training, PROMS, patient reported outcome measures, QoL, quality of life. Primary outcomes are indicated by bold text. Created with BioRender.com

Fig. 2

Overview of COPD-HIIT including participant flow. See Table 5 for specific information of each visit. COPD, chronic obstructive pulmonary disease, HC, healthy controls, HIIT, supramaximal high-intensity interval training, MICT, moderate intensity continuous training, RT, resistance training