Skeletal Muscle in PASC and ME/CFS Patients

NCT05225688 | Active Not Recruiting

• 1 other identifier: NL78394.018.21
• Study Type: observational
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: A common feature in patients with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are skeletal muscle-related symptoms, such as muscle pain, weakness, fatigue and post-exertional malaise. Objective: The primary aim is to determine markers for skeletal muscle structure and function, and circulating factors, in patients with PASC and ME/CFS, and compare with controls. The secondary objective is to determine skeletal muscle structure and function before and after induction of post-exertional malaise, and assess the relationships between the measures obtained from muscle biopsies and parameters of exercise tolerance. Study design: Case-control observational study Study population: Patients with PASC, ME/CFS and healthy human volunteers, 18 - 65 yr old. Intervention (if applicable): none Main study parameters/endpoints: Primary outcome parameters are markers for local inflammation, viral infiltration, mitochondrial respiratory function and myokine concentrations in a muscle biopsy and venous blood before and after induction of post-exertional malaise. Heart rate variability and measures of exercise performance will also be determined. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will be asked to perform physical exercise tests, give muscle biopsies (2 samples), and various blood samples. There is some extent of burden and risk associated with harvesting muscle biopsies and blood samples, however this will be mitigated by the fact that these procedures will only be carried out by trained physicians. Moreover, the scientific gain from obtaining intracellular information outweighs these relatively quick procedures with minimal discomfort afterwards. The acute risks of the physical exercise measurements are negligible. The main risk for patients is that these patients often suffer from post-exertional malaise, which causes the participants to feel fatigued for some time after the maximal exercise test. It is one of the aims to better understand post-exertional malaise.

Conditions

LONG-COVID; Post-acute Sequelae of COVID-19; ME/CFS

Outcome Measures

Primary Outcomes (2)

• Skeletal muscle mitochondrial respiratory function

  7 days

• Local and systemic inflammation markers after induction of post-exertional malaise

  14 days

Secondary Outcomes (3)

• Heart rate variability during post-exertional malaise in LONG-COVID patients

  14 days

• Exercise tolerance in LONG-COVID patients.

  7 days

• Muscle oxygenation derived via near-infrared spectroscopy (NIRS) during exercise in LONG-COVID patients

  7 days

Study Arms (3)

PASC patients

Non-hospitalized covid-19 patients with Post-acute Sequelae of COVID-19

Behavioral: Bike exertion test

Healthy controls

Non-hospitalized covid-19 patients without residual symptoms

Behavioral: Bike exertion test

ME/CFS patients

Patients with ME/CFS

Behavioral: Bike exertion test

Interventions

Bike exertion test BEHAVIORAL

maximal exercise test

Healthy controls; ME/CFS patients; PASC patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

26 non-hospitalized participants with diagnosed PASC, 26 patients with ME/CFS and 30 healthy participants of similar sex, age, BMI and preferably current physical activity levels between the ages of 18-65 years old will be recruited to the study.

You may qualify if:

• In order to be eligible to participate in this study, a subject with PASC must meet all of the following criteria:
• Non-hospitalized individuals with prior confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection by reverse transcription-polymerase chain reaction testing or serology (wantai) testing
• Individuals with diagnosed PASC by a post-covid physician
• \>3 months of symptoms
• Post exertional malaise, according to the DSQ-PEM questionnaire or 1:1 interview with post-covid physician
• No symptoms present before confirmed diagnosis of severe acute respiratory coronavirus 2
• Aged between 18-65 years
• In order to be eligible to participate in this study, a subject with ME/CFS must meet all of the following criteria:
• Fulfill the Canadian Consensus Criteria (CCC)
• Post exertional malaise, according to the DSQ-PEM questionnaire or 1:1 interview with post-covid physician
• \>3 months of symptoms
• Aged between 18-65 years
• Confirmed diagnosis of severe acute respiratory coronavirus2 (SARS-CoV-2) infection by reverse transcription-polymerase chain reaction testing or serology (wantai) testing
• For the healthy controls:
• Aged between 18-65 years

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• History of asthma, stroke, chronic obstructive pulmonary disease, congestive heart failure, heart surgery, or congenital heart diseases
• Severe illness (e.g., active malignancy, CHD, uncontrolled diabetes)
• Current treatment with drugs known to interfere with metabolism e.g. systemic corticosteroids, statins, SGLT2 inhibitors, GLP1 receptor agonists or immune modulatory drugs in the last three months.
• Severe psychiatric or mood disorders
• Insulin pump therapy
• Symptomatic autonomic or distal neuropathy
• BMI \>35 due to adiposity, since this is known to cause difficulties in obtaining muscle biopsies.
• Pregnancy
• Recent acute myocardial infarction (\<6 months)
• Uncontrolled arrhythmia/severe conduction disorder (atrial fibrillation or second/third degree AV block) causing hemodynamic compromise
• Implantable pacemaker or other cardiac device with complete ventricular pacing
• Uncontrolled heart failure with hemodynamic compromise
• Uncontrolled hypertension (Systolic Blood Pressure \>150 mmHg and Diastolic Blood Pressure \> 100 mmHg on repeated measurements)
• Active infection, anaemia, severe renal dysfunction (estimated Glomerular filtration rate \<30 ml/min/1,73m2) likely to significantly impact on exercise performance

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Patient-Led Research Collaborative Long COVID: collaborator

Study Sites (1)

Amsterdam university medical centre AMC

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Related Publications (1)

• Appelman B, Charlton BT, Goulding RP, Kerkhoff TJ, Breedveld EA, Noort W, Offringa C, Bloemers FW, van Weeghel M, Schomakers BV, Coelho P, Posthuma JJ, Aronica E, Joost Wiersinga W, van Vugt M, Wust RCI. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nat Commun. 2024 Jan 4;15(1):17. doi: 10.1038/s41467-023-44432-3.

  PMID: 38177128 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Frozen tissue, whole blood

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue Syndrome, Chronic

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 4, 2022
• Study Start: January 3, 2022
• Primary Completion: February 15, 2024
• Study Completion: December 1, 2025
• Last Updated: August 6, 2024

Record last verified: 2024-08

Locations

NL (1)