PEM, a Starting Point to Investigate ME/CFS

Condition(s) studied

Investigational drug(s) / intervention(s)

No intervention is planned: Investigation of the pathophysiology of PEM in ME/CFS patients and matched controls

Study 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.

Eligibility

Primary outcome measure(s)

• Cardiovascular parameters (Heart rate and blood pressure) — 2023-2027
  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.
• Short maximal voluntary contraction — 2023-2027
  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.
• Submaximal voluntary contractions (20%,40%, 60% of the short MVC) — 2023-2027
  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.
• Sustained maximal voluntary contraction of the FDI — 2023-2027
  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.
• Cognitive parameters (stroop task) — 2023-2027
  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.
• BOLD activation — 2023-2027
  Blood oxygenation level dependent (BOLD): changes both in oxy- and deoxyhemoglobin concentration. Brain activation in different tasks will be compared between groups and sessions.
• Arterial Spin Labeling (ASL) — 2023-2027
  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.
• Cerebral oxygenation (near infrared spectroscopy) — 2023-2027
  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.

Trial sites (1)

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