PEM, a Starting Point to Investigate and Understand ME/CFS
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Cardiovascular parameters (Heart rate and blood pressure)
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and be able to complete all study procedures
- •Able to provide informed consent
- •Additional inclusion criteria for ME/CFS patients
- •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-
- •The persistent fatigue may have an acute onset or become progressively worse over 6 months.
排除标准
- •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.
- •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
- •Being colorblind
- •Additional exclusion criteria for control subjects:
- •performing high intensity or moderate intensity activities more than 30 minutes per week
- •substantial fatigue as determined using MFIS fatigue questionnaire >30
结局指标
主要结局
Cardiovascular parameters (Heart rate and blood pressure)
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- Knee extension force(2023-2027)
- 30 Chair to stand test(2023-2027)
- Handgrip force (kg)(2023-2027)
- Activity monitor(2023-2027)
- Blood samples(2023-2027)
- Chalder fatigue scale(2023-2027)
- SF-36(2023-2027)
- DePaul Symptoms Questionnaire 2 (DSQ-2)(2023-2027)
- Bell disability scale(2023-2027)
- Pittsburgh sleep quality index(2023-2027)
- Hospital Anxiety and Depression Scale(2023-2027)
- Composite Autonomic Symptom Score 31(2023-2027)
- Modified Fatigue Impact Scale (MFIS)(2023-2027)
- DePaul Post-Exertional Malaise Questionnaire (DPEMQ)(2023-2027)
- EQ-5D(2023-2027)
- Symptom severity score (SSS-12)(2023-2027)