Feasibility of an Augmented Two-Day Step Test and Causal Modeling for Post-Exertional Symptom Exacerbation in Post Covid-19 Syndrome (REVEAL)

Universitair Ziekenhuis Brussel

Status: Completed

Conditions: Long COVID

Treatments: Device: Portable mask for respiratory gas analysis; Device: Cardio-pulmonary exercise test

Study type: Interventional

Funder types: Other

Identifiers

NCT06933017

2024-EDW-REVEAL

G075423N (Other Grant/Funding Number)

Details and patient eligibility

About

This study aims to evaluate exercise capacity and identify causes of Post-Exertional Symptom Exacerbation (PESE) in individuals with Long COVID. The investigators will compare the effectiveness of the Two-Day 6-Minute Incremental Step Test (6MIST) and the Cardiopulmonary Exercise Test (CPET) in detecting PESE. Additionally, the investigators will assess metabolism, mitochondrial function, autonomic symptoms, psychological factors, and physical activity. Participants will complete both the Two-Day 6MIST and the Two-Day CPET, with a one-month gap between them. Each test is performed on two consecutive days to assess the delayed symptom response. The subjective symptoms of PESE will also be measured through questionnaires. To explore potential causes of PESE, the investigators will measure metabolism using indirect calorimetry, bioelectrical impedance analysis and food diaries, mitochondrial dysfunction with NIRS technology, autonomic symptoms using the COMPASS-31 questionnaire, psychological factors with questionnaires and physical activity levels using an activity tracker. This study will determine if the Two-Day Step Test (6MIST) is a feasible alternative to the two-day CPET for measuring PESE and will help uncover underlying mechanisms contributing to symptom exacerbation.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥18 years old
• Long COVID patients following the World Health Organization (WHO) criteria: "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation"
• Previously active as described in the WHO recommendations for physical activity (minimal 150 minutes/week of moderate intensity aerobic physical activity OR minimal 75 minutes of vigorous intensity activity/week OR an equivalent combination of moderate- and vigorous-intensity activity throughout the week)
• Patient suffers from PESE as defined by the DePaul Symptom Questionnaire PEM (Post-Exertional Malaise) subscale
• Able to understand and sign written informed consent in Dutch, French or English

Exclusion criteria

• Any pre-existing conditions or new medical diagnosis that can alternatively explain the current symptoms
• Being unable to perform a cycle ergometer test as decided upon by the medical study team members
• Suffering from Chronic Obstructive Pulmonary Disease (COPD) GOLD classification category 2,3 or 4 (by the Global Initiative for Chronic Obstructive Lung Disease)
• Allergies to medical adhesive bandages
• Skin conditions aggravated by sunlight including Porphyria
• Participation in other interventional trials
• Mitochondrial diseases
• Pregnancy
• Lactation

Trial design

Primary purpose: Device Feasibility

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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25 participants in 2 patient groups

Two day 6-Minute Incremental Step Test (6 MIST)

Experimental group

Description:

The 6-Minute Incremental Step Test (6MIST) is an incremental pace stationary stepping test wherein the pace increases by 5 steps every 30 seconds using a metronome, lasting a maximum of 6 minutes. Clinical cardio-respiratory variables are simultaneously recorded. A portable metabolic analyzer, the Calibre Biometric Tracker, will be utilized to evaluate VO2 and VE (TV and RR). The Polar Sense of the Polar 10 heart rate monitor will measure HR on a continuous basis. The Train-Red Fyer NIRS Muscle Oxygen Sensor will be utilized to gather oxygenation data from muscle tissue.

Treatment:

Device: Portable mask for respiratory gas analysis

Two day Cardio-Pulmonary Exercise Test (CPET)

Active Comparator group

Description:

Prior to the CPET, spirometry is executed to predict the Maximum Voluntary Ventilation (MVV) from the Forced Expiratory Volume in one second (FEV1).The test is performed on a bicycle. The protocol is customized for each patient to achieve a fatigue-limited exercise duration of 8 to12 minutes. The predicted peak wattage is calculated according to a formula and by taking into account the patient's clinical profile. Patients start at 0 watts per minute. The intensity is increased until exhaustion (incremental step protocol) or if the test needs to be stopped for safety reasons. Patients are connected to an electrocardiogram (ECG), oximeter and blood pressure cuff. A mouthpiece is used to collect information about gas exchange.

Treatment:

Device: Cardio-pulmonary exercise test