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

Not Applicable

Recruiting

• Conditions: Long COVID

• Registration Number: NCT06933017
• Lead Sponsor: Universitair Ziekenhuis Brussel

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study Start: 2025-03-20
• Study First Submitted: 2025-04-03
• Study First Submitted QC: 2025-04-16
• Last Update Submitted: 2025-04-16
• Study First Posted: 2025-04-17
• Last Update Posted: 2025-04-17
• Primary Completion: 2025-07
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
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	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.
Difference in Rate of Perceived Exertion (RPE) measured with the CPET compared to measured with the Calibre device	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.
Resting Energy Expenditure (kcal/kg/day), measured through Indirect Calorimetry (IC)	Baseline (measured once, during the first study visit)	Measuring Resting Energy Expenditure as part of the Directed Acyclic Graph (DAG).
Total Energy Expenditure (TEE) in kcal/kg/day, measured through Indirect Calorimetry (IC)	Baseline (measured once during the first study visit)	Measuring Total Energy Expenditure as part of the DAG.
Phase angle (degrees), measured through Bioelectrical Impedance Analysis (BIA)	Baseline (measured once during the first study visit)	Measuring Phase Angle as part of the DAG.
Muscle mass (kg/m2), measured through Bioelectrical Impedance Analysis (BIA)	Baseline (measured once during the first study visit)	Measuring muscle mass as part of the DAG.
Fat mass index (kg/m2), measured through Bioelectrical Impedance Analysis (BIA)	Baseline (measured once during the first study visit)	Measuring fat mass index as part of the DAG.
Fat-free mass index (kg/m²), measured through Bioelectrical Impedance Analysis (BIA)	Baseline (measured once during the first study visit)	Measuring fat free mass index as part of the DAG.
Fat to fat-free mass ratio, measured through bioelectrical impedance analysis (BIA)	Baseline (measured once during the first study visit)	Measuring fat-free mass ratio as part of the DAG.
Hydration (%), measured through Bioelectrical Impedance Analysis (BIA)	Baseline (measured once during the first study visit)	Measuring hydration as part of the DAG.
Ratio of calorie and protein intake to individual need, measured through food diaries	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.
Mean daily intake of calories, fats, proteins, and carbohydrates, measured through food diaries	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.
Oxygen availability as the partial pressure of oxygen (mitoPO2) (mmHg), measured through Near-infrared spectroscopy (NIRS)	Baseline (measured once during the first study visit)	Measuring oxygen availability as the partial pressure of oxygen as part of the DAG.
Kinesiophobia with the Tampa Scale for Kinesiophobia (TSK)	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.
Ability to bounce back after stressful events with the Brief Resilience Scale (BRS) Questionnaire	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.
Coping style with the Ways of Coping (WAYS) Questionnaire	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.
Autonomic symptoms, measured with the COMPASS-31 questionnaire	Baseline (measured once during the first study visit)	Measuring autonomic symptoms as part of the DAG.
Level of Physical Activity (PA) and sedentary behavior assessed by accelerometry (activity tracker)	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 Outcome Measures

Name	Time	Method
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)	From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST
Change from Day 1 to Day 2 in VE/VO2 slope during experimental sessions 1 and 2 (CPET and 6 MIST)	From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST
Change from Day 1 to Day 2 in VO2/HR slope (= O2 pulse) during experimental sessions 1 and 2 (CPET and 6 MIST)	From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST
Change from Day 1 to Day 2 in Respiratory Exchange Ratio (RER) = VCO2/VO2 during experimental sessions 1 or 2 (CPET)	From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
Change from Day 1 to Day 2 in Cardiorespiratory Optimal Point (COP) = VO2/VE during experimental session 1 or 2 (CPET)	From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
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)	From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
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))	From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST)
Change from Day 1 to Day 2 in Workload (Watts) at first ventilatory threshold during experimental session 1 or 2 (CPET)	From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
Change from Day 1 to Day 2 in Workload (Watts) at peak during experimental session 1 or 2 (CPET)	From Day 1 to Day 2 during experimental session 1 or 2 (CPET)
Change from Day 1 to Day 2 in Heart Rate (bpm) peak during experimental sessions 1 and 2 (CPET & 6MIST))	From Day 1 to Day 2 during experimental sessions 1 and 2 (CPET & 6MIST)

Trial Locations

Locations (1)

Universitair Ziekenhuis Brussel; 🇧🇪 Brussels, Jette, Belgium