Clinical trial NCT06933017: Feasibility of an Augmented Two-Day Step Test and Causal Modeling for Post-Exertional Symptom Exacerbation in Post Covid-19 Syndrome
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Long COVID
Keywords: long covid
PEM
Post-Exertional Malaise
CPET
6MIST
Fatigue
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: Vrije Universiteit Brussel, Jette, Belgium
First posted: 2025-04-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Feasibility study in a cross-over model. The investigators calculated 40% drop out because this protocol presents considerable challenges for participants to complete.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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)
measure: Difference in Rate of Perceived Exertion (RPE) measured with the CPET compared to measured with the Calibre device
timeFrame: 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.]
measure: Resting Energy Expenditure (kcal/kg/day), measured through Indirect Calorimetry (IC)
timeFrame: Baseline (measured once, during the first study visit)
measure: Total Energy Expenditure (TEE) in kcal/kg/day, measured through Indirect Calorimetry (IC)
timeFrame: Baseline (measured once during the first study visit)
measure: Phase angle (degrees), measured through Bioelectrical Impedance Analysis (BIA)
timeFrame: Baseline (measured once during the first study visit)
measure: Muscle mass (kg/m2), measured through Bioelectrical Impedance Analysis (BIA)
timeFrame: Baseline (measured once during the first study visit)
measure: Fat mass index (kg/m2), measured through Bioelectrical Impedance Analysis (BIA)
timeFrame: Baseline (measured once during the first study visit)
measure: Fat-free mass index (kg/m²), measured through Bioelectrical Impedance Analysis (BIA)
timeFrame: Baseline (measured once during the first study visit)
measure: Fat to fat-free mass ratio, measured through bioelectrical impedance analysis (BIA)
timeFrame: Baseline (measured once during the first study visit)
measure: Hydration (%), measured through Bioelectrical Impedance Analysis (BIA)
timeFrame: Baseline (measured once during the first study visit)
measure: Ratio of calorie and protein intake to individual need, measured through food diaries
timeFrame: Between day 1 of study visit and day 1 of experimental session
measure: Mean daily intake of calories, fats, proteins, and carbohydrates, measured through food diaries
timeFrame: Between day 1 of study visit and day 1 of experimental session
measure: Oxygen availability as the partial pressure of oxygen (mitoPO2) (mmHg), measured through Near-infrared spectroscopy (NIRS)
timeFrame: Baseline (measured once during the first study visit)
measure: Kinesiophobia with the Tampa Scale for Kinesiophobia (TSK)
timeFrame: Baseline (measured once during the first study visit)
measure: Ability to bounce back after stressful events with the Brief Resilience Scale (BRS) Questionnaire
timeFrame: Baseline (measured once during the first study visit)
measure: Coping style with the Ways of Coping (WAYS) Questionnaire
timeFrame: Baseline (measured once during the first study visit)
measure: Autonomic symptoms, measured with the COMPASS-31 questionnaire
timeFrame: Baseline (measured once during the first study visit)
measure: Level of Physical Activity (PA) and sedentary behavior assessed by accelerometry (activity tracker)
timeFrame: During 7 days before the first experimental session
Secondary outcomes:
measure: 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)
timeFrame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
measure: 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))
timeFrame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST)
measure: Change from Day 1 to Day 2 in Workload (Watts) at first ventilatory threshold during experimental session 1 or 2 (CPET)
timeFrame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
measure: Change from Day 1 to Day 2 in Workload (Watts) at peak during experimental session 1 or 2 (CPET)
timeFrame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
measure: Change from Day 1 to Day 2 in Heart Rate (bpm) peak during experimental sessions 1 and 2 (CPET & 6MIST))
timeFrame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST)
measure: 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)
timeFrame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST
measure: Change from Day 1 to Day 2 in VE/VO2 slope during experimental sessions 1 and 2 (CPET and 6 MIST)
timeFrame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST
measure: Change from Day 1 to Day 2 in VO2/HR slope (= O2 pulse) during experimental sessions 1 and 2 (CPET and 6 MIST)
timeFrame: From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST
measure: Change from Day 1 to Day 2 in Respiratory Exchange Ratio (RER) = VCO2/VO2 during experimental sessions 1 or 2 (CPET)
timeFrame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
measure: Change from Day 1 to Day 2 in Cardiorespiratory Optimal Point (COP) = VO2/VE during experimental session 1 or 2 (CPET)
timeFrame: From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
Other outcomes:
measure: Vaccination status of the participant
timeFrame: Baseline (inquired during the first study visit)
measure: Date of birth of the participant
timeFrame: Baseline (inquired during the first study visit)
measure: Ethnicity of the participant
timeFrame: Baseline (inquired during the first study visit)
measure: BMI (kg/m²)
timeFrame: Baseline (calculated during the first study visit)
measure: Hospitalization for COVID-19
timeFrame: Baseline (inquired during the first study visit)
measure: Educational level of the participant
timeFrame: Baseline (inquired during the first study visit)
measure: Employement status of the participant
timeFrame: Baseline (inquired during the first study visit)
measure: Native language of the participant
timeFrame: Baseline (inquired during the first study visit)
Locations:
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
state: Brussels
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
state: Jette
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Elisabeth De Waele, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: