PEM, a Starting Point to Investigate ME/CFS

NCT07715838 | Recruiting DMC

• 1 other identifier: UMCG 17463
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Exercise is an important contributor to general health and is considered a potential remedy for chronic diseases. This is in strong contrast with the observation that in most myalgic encephalomyelitis (ME/CFS) patients exercise aggravates their symptoms. Recently, post-exertional malaise (PEM) is defined as the key symptom of ME/CFS. The etiology and pathophysiological mechanisms underlying ME/CFS are still unknown and objective diagnostic criteria are not available. Various hypotheses are postulated including disorders of several organ systems but the heterogenous presentation of symptoms in patients, and the multisystem deficits complicate reaching an all-encompassing hypothesis. It seems therefore reasonable to focus on the key symptom, i.e., PEM. PEM can be induced by minor cognitive or physical exertion and can be assessed with questionnaires. Acute physical activity triggers complex cardiovascular, metabolic, and molecular responses and for ME/CFS, hence it is important to understand the relation between these acute processes and the prolonged presentation of aggravated symptoms (PEM). We therefore want to measure metabolites, cardiovascular responses, cognitive performance, muscle force and fatigability in 50 patients and 50 controls matched on group level for sex, age, and activity. To follow changes in these parameters we perform time-series analysis, including data obtained before, during and after task performance. Besides understanding these interactions, it is also essential to understand how these acute and prolonged responses affect behaviour and perception.

Conditions

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome

Keywords

Post exertional malaise

Outcome Measures

Primary Outcomes (8)

• Cardiovascular parameters (Heart rate and blood pressure)

  Heart rate (bpm) and blood pressure (mmHg) are measured with a continuous non-invasive monitoring system (Finapres Midi). The BP sensor is positioned around the middle finger on the second phalanx of the left hand and subjects must hold their arm at breast level. The recorded values during T1 and T2 will be compared between tasks, as well as between groups and sessions.

  2023-2027

• Short maximal voluntary contraction

  Short isometric maximal voluntary contractions (MVC) of the right index finger abductor (FDI). The maximal index finger abduction force (newton) is measured with a force transducer which is held by the participant. The measurement is repeated 3 times per hand and the highest value is taken. On the second and third repetition, a superimposed twitch stimulation (SIT) will be induced to assess the voluntary activation during maximal contraction.

  2023-2027

• Submaximal voluntary contractions (20%,40%, 60% of the short MVC)

  The participant is asked to produce force at different submaximal force targets (20%, 40%, 60%). The targets are presented on a monitor and subjects get online feedback of the target force and their produced force.

  2023-2027

• Sustained maximal voluntary contraction of the FDI

  The participant performs a maximal contraction for 2 minutes. During the 2 minutes contraction 7 SIT stimulation are given to the subject to assess voluntary muscle activation during a fatiguing task.

  2023-2027

• Cognitive parameters (stroop task)

  This test assesses the ability to inhibit cognitive interference, which occurs when the processing of a stimulus feature affects the simultaneous processing of another attribute of the same stimulus. Participants see a word describing a colour on a screen, the word is written in the same or different colour than the word they will read. They are asked to press a yes or no button to indicate whether the colour of the word and the meaning of the word matches (yes) or not (no). The number of correct answers and the reaction time will be assessed.

  2023-2027

• BOLD activation

  Blood oxygenation level dependent (BOLD): changes both in oxy- and deoxyhemoglobin concentration. Brain activation in different tasks will be compared between groups and sessions.

  2023-2027

• Arterial Spin Labeling (ASL)

  Is a non-invasive fMRI technique that uses arterial water as an endogenous tracer to measure cerebral blood flow. ASL provides reliable absolute quantification of cerebral blood flow with high spatial and temporal resolution. Perfusion data are used to identify patients suffering from impaired autoregulation of cerebral blood flow and to obtain associations with cardiovascular responses and muscle fatigue.

  2023-2027

• Cerebral oxygenation (near infrared spectroscopy)

  Oxy- and deoxyhemoglobine concentrations are measured at the prefrontal cortex and leg muscle with a non-invasive near infrared spectroscopy device (NIRS), where small sensors are positioned on the forehead and the quadriceps muscle. For this measurement a standardized vascular occlusion test will be performed on the quadriceps muscle to assess the local tissue oxygen consumption and the microvascular reperfusion and reactivity. This measurement will be used as calibration to normalize per subject the oxy- and deoxyhemoglobin concentrations allowing for comparisons between subjects. The oxygenated and deoxygenated values for the prefrontal cortex and leg muscle will be compared across tasks, groups and sessions.

  2023-2027

Secondary Outcomes (16)

• 30 Chair to stand test

  2023-2027

• Handgrip force (kg)

  2023-2027

• Activity monitor

  2023-2027

• Blood samples

  2023-2027

• Knee extension force

  2023-2027

Study Arms (2)

ME/CFS

50 patients diagnosed with ME/CFS according to the International Consensus Criteria (ICC) and Canadian Consensus Criteria (CCC) will be included

Other: No intervention is planned

Control

50 sex, age and activity matched controls will be included

Other: No intervention is planned

Interventions

No intervention is planned OTHER

Investigation of the pathophysiology of PEM in ME/CFS patients and matched controls

Control; ME/CFS

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

Patients with diagnosed ME/CFS according to the international consensus criteria or the canadian consensus criteria and 50 controls matched on group level for age, sex, and activity.

You may qualify if:

• Willing and be able to complete all study procedures
• Able to provide informed consent
• ME/CFS patients have to meet the criteria of the ICC OR CCC.
• A self-reported illness narrative of the development of persistent fatigue and post-exertional malaise according to the DSQ-2. The persistent fatigue may have an acute onset or become progressively worse over 6 months.

You may not qualify if:

• Use of immune-modulating drugs in the past 3 months.
• A serious medical condition that may explain symptoms similar to ME/CFS, such as cancer, coronary artery disease, uncontrolled diabetes, chronic infection (hepatitis B and C, tuberculosis, HIV), inflammatory diseases, autoimmune diseases (e.g. such as rheumatoid arthritis, lupus or polymyositis), severe COPD or other severe persistent respiratory disease, severe anemia, renal failure, Addison's or Cushing's disease or severe neurological disease (such as Parkinson's disease).
• History of head injury with loss of consciousness or amnesia lasting greater than a few seconds within last five years or lasting greater than 5 minutes at any point during their lifetime. Persons with medical record evidence of post-concussive symptoms lasting more than six months are also excluded.
• Suspected, probable, or confirmed Lyme disease
• Current or substance use disorder within last 5 years
• A mood disorder or other psychiatric diagnosis prior to a diagnosis of ME/CFS.
• Pregnant, actively seeking to become or breastfeeding in the past 12 months.
• BMI \>35.
• having cognitive or communication problems which reduces the capacity to understand instructions.
• planned a change in medication during the testing period.
• Use of medication that affects the blood pressure (e.g. Beta-blockers, fludrocortisone, vasoconstrictors).
• Participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study.
• Claustrophobia
• Current (within 1 week) use of prescription or over-the-counter medications, herbal supplements, or nutraceuticals that may influence brain excitability that the potential participant is either unwilling or clinically unable to safely wean off for the duration of the period of the visits. The possibility for a potential participant to be weaned off medication will be cooperatively determined by both the clinical investigative team and personal physicians. Examples of medications that influence brain excitability include tricyclic antidepressants, hypnotic, antiepileptic, antipsychotic medication, stimulants, antihistamines, muscle relaxants, dopaminergic medications, and sleep medications.
• Use of B12 high dosage injections

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

UMC Groningen

Groningen, 9713VB, Netherlands

RECRUITING

MeSH Terms

Conditions

Fatigue Syndrome, Chronic

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Inge Zijdewind, Dr

CONTACT

0625647190; c.a.t.zijdewind@umcg.nl

Leda Maffei

CONTACT

0625647190; l.b.maffei@umcg.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: July 21, 2026
• Study Start: May 1, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)