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Completed

NCT Number: NCT06933017

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

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.

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Key information

Conditions

Long COVID COVID-19 Chronic Disease Coronaviridae Infections Coronavirus Infections Disease Attributes Fatigue Infections Lung Diseases Nidovirales Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pneumonia, Viral Post-Acute COVID-19 Syndrome Post-Infectious Disorders RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Signs and Symptoms Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Universitair Ziekenhuis Brussel, Jette, Brussels Capital, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Portable mask for respiratory gas analysis

Device

This is a portable mask, which is connected to the SplendoHealth app. The Polar sens 10 heartrate monitor and TrainRed NIRS device are also connected to this app. The three devices (mask, heartrate monitor and NIRS) are measuring respiratory gases, heart rate and muscle tissue oxygenation simultanuously and at the end of the 6 min step test, you get an individual cardiorespiratory fitness report.

Other names: SplendoHealth app

Cardio-pulmonary exercise test

Device

Golden standard for measuring PEM: the double cardio-pulmonary exercise test on a bike.

Other names: CPET

Primary outcomes

  1. Difference in oxygen uptake at peak (VO2 peak) between day 1 and day 2 measured with the CPET compared to measured with the Calibre device

    Time frame: From day 1 and day 2 of experimental session 1 to day 1 and day 2 of experimental session 2, one month apart (±10 days)

    The goal is to show that the Calibre device is a feasible alternative to the CPET.

  2. Difference in Rate of Perceived Exertion (RPE) measured with the CPET compared to measured with the Calibre device

    Time frame: RPE will be measured during two experimental sessions, each with two days, one month apart. On day 1, RPE is recorded 15 minutes (±15 min) before and after the test. On day 2, RPE is measured 24 hours (±120 min) after test 1 and before test 2.]

    Rate of Perceived Exertion is measured with the Borg RPE Scale which is a subjective measurement instrument. The scores range from 6 to 20, in which 6 is equal to no exertion at all and 20 is maximal exertion.

  3. Resting Energy Expenditure (kcal/kg/day), measured through Indirect Calorimetry (IC)

    Time frame: Baseline (measured once, during the first study visit)

    Measuring Resting Energy Expenditure as part of the Directed Acyclic Graph (DAG).

  4. Total Energy Expenditure (TEE) in kcal/kg/day, measured through Indirect Calorimetry (IC)

    Time frame: Baseline (measured once during the first study visit)

    Measuring Total Energy Expenditure as part of the DAG.

  5. Phase angle (degrees), measured through Bioelectrical Impedance Analysis (BIA)

    Time frame: Baseline (measured once during the first study visit)

    Measuring Phase Angle as part of the DAG.

  6. Muscle mass (kg/m2), measured through Bioelectrical Impedance Analysis (BIA)

    Time frame: Baseline (measured once during the first study visit)

    Measuring muscle mass as part of the DAG.

  7. Fat mass index (kg/m2), measured through Bioelectrical Impedance Analysis (BIA)

    Time frame: Baseline (measured once during the first study visit)

    Measuring fat mass index as part of the DAG.

  8. Fat-free mass index (kg/m²), measured through Bioelectrical Impedance Analysis (BIA)

    Time frame: Baseline (measured once during the first study visit)

    Measuring fat free mass index as part of the DAG.

  9. Fat to fat-free mass ratio, measured through bioelectrical impedance analysis (BIA)

    Time frame: Baseline (measured once during the first study visit)

    Measuring fat-free mass ratio as part of the DAG.

  10. Hydration (%), measured through Bioelectrical Impedance Analysis (BIA)

    Time frame: Baseline (measured once during the first study visit)

    Measuring hydration as part of the DAG.

  11. Ratio of calorie and protein intake to individual need, measured through food diaries

    Time frame: Between day 1 of study visit and day 1 of experimental session

    Adequacy of feeding: the ratio between intake of calories and proteins and the individual need.

    Record of all food and drinks consumed over a 3-day period as part of the DAG.

  12. Mean daily intake of calories, fats, proteins, and carbohydrates, measured through food diaries

    Time frame: Between day 1 of study visit and day 1 of experimental session

    Mean daily intake: calories, fats, proteins, carbohydrates Record of all food and drinks consumed over a 3-day period.

  13. Oxygen availability as the partial pressure of oxygen (mitoPO2) (mmHg), measured through Near-infrared spectroscopy (NIRS)

    Time frame: Baseline (measured once during the first study visit)

    Measuring oxygen availability as the partial pressure of oxygen as part of the DAG.

  14. Kinesiophobia with the Tampa Scale for Kinesiophobia (TSK)

    Time frame: Baseline (measured once during the first study visit)

    The Tampa Scale for Kinesiophobia (TSK) consists of 17 statements, each scored from 1 to 4, with 1 being 'strongly disagree' and 4 being 'strongly agree.' Higher scores indicate greater kinesiophobia. Measuring kinesiophobia as part of the DAG.

  15. Ability to bounce back after stressful events with the Brief Resilience Scale (BRS) Questionnaire

    Time frame: Baseline (measured once during the first study visit)

    The Brief Resilience Scale (BRS) consists of 6 statements, each scored from 1 to 4, with 1 being 'strongly disagree' and 4 being 'strongly agree.' Higher scores indicate greater resilience. Measuring resilience as part of the DAG.

  16. Coping style with the Ways of Coping (WAYS) Questionnaire

    Time frame: Baseline (measured once during the first study visit)

    Sixty-six statements about a stressful situation that participants experienced in the past week, for which they need to give a score ranging from 0 to 3, with 0 being "does not apply" or "not used," and 3 being "used a great deal". Measuring coping style as part of the DAG.

  17. Autonomic symptoms, measured with the COMPASS-31 questionnaire

    Time frame: Baseline (measured once during the first study visit)

    Measuring autonomic symptoms as part of the DAG.

  18. Level of Physical Activity (PA) and sedentary behavior assessed by accelerometry (activity tracker)

    Time frame: During 7 days before the first experimental session

    Using an actigraph, with a frequenncy of 60 Hertz, that participants wear at their hip on their dominant side. Measuring physical activity as part of the DAG.

Secondary outcomes

  1. Change from Day 1 to Day 2 in Oxygen Uptake at First Ventilatory Threshold (VO₂ in ml/min/kg) during experimental session 1 or 2 (CPET)

    Time frame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)

  2. Change from Day 1 to Day 2 in Oxygen uptake at peak (VO2 in ml/min/kg) during experimental session 1 and 2 (CPET & 6MIST))

    Time frame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST)

  3. Change from Day 1 to Day 2 in Workload (Watts) at first ventilatory threshold during experimental session 1 or 2 (CPET)

    Time frame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)

  4. Change from Day 1 to Day 2 in Workload (Watts) at peak during experimental session 1 or 2 (CPET)

    Time frame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)

  5. Change from Day 1 to Day 2 in Heart Rate (bpm) peak during experimental sessions 1 and 2 (CPET & 6MIST))

    Time frame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST)

  6. Change from Day 1 to Day 2 in Ventilation (VE) (Tidal Volume (TV) and Respiration Rate (RR)) during experimental sessions 1 and 2 (CPET 1 6MIST)

    Time frame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST

  7. Change from Day 1 to Day 2 in VE/VO2 slope during experimental sessions 1 and 2 (CPET and 6 MIST)

    Time frame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST

  8. Change from Day 1 to Day 2 in VO2/HR slope (= O2 pulse) during experimental sessions 1 and 2 (CPET and 6 MIST)

    Time frame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST

  9. Change from Day 1 to Day 2 in Respiratory Exchange Ratio (RER) = VCO2/VO2 during experimental sessions 1 or 2 (CPET)

    Time frame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)

  10. Change from Day 1 to Day 2 in Cardiorespiratory Optimal Point (COP) = VO2/VE during experimental session 1 or 2 (CPET)

    Time frame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)

Other outcomes

  1. Vaccination status of the participant

    Time frame: Baseline (inquired during the first study visit)

    Is the participant vaccinated or not, and with which vaccine.

  2. Date of birth of the participant

    Time frame: Baseline (inquired during the first study visit)

    Date of birth of the participant. This is needed to make sure the participant is older than 18.

  3. Ethnicity of the participant

    Time frame: Baseline (inquired during the first study visit)

    What is the ethnicity of the participant. (White, Hispanic/Latino, Black/African/African American, Asian, Native American/Indigenous)

  4. BMI (kg/m²)

    Time frame: Baseline (calculated during the first study visit)

  5. Hospitalization for COVID-19

    Time frame: Baseline (inquired during the first study visit)

    Has the participant been hospitalized for his or her COVID infection, yes or no.

    If yes, has the participant been hospitalized in the ICU or not.

  6. Educational level of the participant

    Time frame: Baseline (inquired during the first study visit)

    The highest degree of the participant.

  7. Employement status of the participant

    Time frame: Baseline (inquired during the first study visit)

    The current employment status of the participant (employed full time or part-time, unemployed looking for work, unemployed not looking for work, self-employed, unable to work, student, retired).

  8. Native language of the participant

    Time frame: Baseline (inquired during the first study visit)

    Native language of the participant (Dutch, French, English, German, Arabic, Other)

Sponsors and collaborators

Lead sponsor

Universitair Ziekenhuis Brussel

Other

Collaborators

  • Vrije Universiteit Brussel

Registry information

Official study title

Feasibility Study of the Augmented Two-Day 6-Minute Incremental Step Test and Causal Exploration Through a Directed Acyclic Graph and Structural Equation Model for Post-Exertional Symptom Exacerbations in Long COVID Patients

Acronym: REVEAL

Important dates

Study start
2025
Primary completion
2025
Study completion
2025
First posted
Apr 17, 2025
Registry last updated
Jul 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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