Analysis of Post-exertional Malaise Using a Two-day CPET in People With ME/CFS

Study Overview
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Brief Summary
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This study aims to collect and identify key outcome measures or disease parameters in ME/CFS that are altered during elevated symptoms relative to baseline by gathering information before and after symptom provocation using a two-day cardiopulmonary exercise test.

Detailed Description
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The phenomenon of post-exertional malaise (PEM), in which an ME/CFS patient's symptoms are elevated following even low-level exertion, is a hallmark feature of the disease. The cause of PEM, like the cause of ME/CFS, is not understood. This study aims to utilize a two-day CPET to invoke PEM. This provides a unique opportunity to collect data on how key outcome measures or disease parameters are altered during elevated symptoms relative to baseline within each patient by gathering information before and after symptom provocation. A total of 90 participants and 90 controls will undergo CPET testing. Participation will be split amongst three different sites (Ithaca, NY, New York, NY, and Los Angeles, CA). Subjects will be located in urban and rural areas to establish relatively diverse study populations. This study is a component of the Cornell ME/CFS Collaborative Research Center (CRC). Blood samples taken before and after CPET will be utilized in associated projects with the Cornell ME/CFS CRC. CPET data along with the analysis of blood samples has great potential to reveal why exercise negatively affects ME/CFS patients and thus perhaps why patients are also impaired even before increasing their activity level.

Official Title
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Probing Metabolism, Circulating Inflammatory Molecules, Extracellular Vesicles and Immune Dysregulation in Individual Immune Cells in ME/CFS

Conditions
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Myalgic Encephalomyelitis, Chronic Fatigue Syndrome

Intervention / Treatment
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* Other: Two-day cardiopulmonary exercise test


Participation Criteria
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Eligibility Criteria
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Adults with ME/CFS: Inclusion Criteria: Diagnosed with ME/CFS Adults 18 to 70 years of age Exclusion Criteria: Recent history of panic attacks within the past 6 months Diagnosis of schizophrenia, major depressive disorder, bipolar disorder, or an anxiety disorder such as OCD or PTSD Hospitalized for a psychological condition within the last 6 months Unwilling to stop taking nutritional supplements, including probiotics, two weeks before the exercise tests. Unwilling to stop pain medication and stimulant medication two days before the exercise tests. Smoker, or stopped smoking less than 1 year ago Pregnant or breastfeeding Diabetic Have an orthopedic limitation that prohibits cycle exercise Excessive alcohol consumption Healthy Volunteers: Inclusion Criteria: Healthy Low-active Adults 18 to 70 years of age Exclusion Criteria: Recent history of panic attacks within the past 6 months Diagnosis of schizophrenia, major depressive disorder, bipolar disorder, or an anxiety disorder such as OCD or PTSD Hospitalized for a psychological condition within the last 6 months Unwilling to stop taking nutritional supplements, including probiotics, two weeks before the exercise tests. Unwilling to stop pain medication and stimulant medication two days before the exercise tests. Smoker, or stopped smoking less than 1 year ago Pregnant or breastfeeding Diabetic Have an orthopedic limitation that prohibits cycle exercise Excessive alcohol consumption

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ME/CFS<br>Adults with ME/CFS | Other: Two-day cardiopulmonary exercise test<br>* A series of two cardiopulmonary exercise tests (CPETs) performed over two days. Participants will perform a CPET and then will return approximately 24 hours later to perform the second CPET. The CPET begins with 3 minutes of seated rest followed by cycling during incremental workloads which increases 15 watts throughout each minute of exercise. The participant will cycle until volitional exhaustion and/or the participant and/or test administrator determines to stop the test. Actual exercise time usually varies between 8-10 minutes.<br>|
| Active Comparator: Healthy controls<br>Healthy, low-active adults | Other: Two-day cardiopulmonary exercise test<br>* A series of two cardiopulmonary exercise tests (CPETs) performed over two days. Participants will perform a CPET and then will return approximately 24 hours later to perform the second CPET. The CPET begins with 3 minutes of seated rest followed by cycling during incremental workloads which increases 15 watts throughout each minute of exercise. The participant will cycle until volitional exhaustion and/or the participant and/or test administrator determines to stop the test. Actual exercise time usually varies between 8-10 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of oxygen consumed at peak effort | Volume of oxygen consumed at peak effort during CPET 1 and during CPET 2. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Volume of oxygen consumed at ventilatory/anaerobic threshold (VAT) | VAT is a non-invasive surrogate measure for anaerobic threshold, which is indicated during incremental exercise by a non-linear increase in rate of carbon dioxide production relative to rate of oxygen consumption. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Rate of work performed at peak effort | Rate of work performed at peak effort during CPET 1 and during CPET 2. Rate of work is measured in Watts. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Rate of work performed at VAT | Rate of work performed at VAT during CPET 1 and during CPET 2. Rate of work is measured in Watts. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Heart rate at peak effort | Heart rate at peak effort during CPET 1 and during CPET 2. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Heart rate at VAT | Heart rate at VAT during CPET 1 and during CPET 2. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Systolic blood pressure at seated rest | Systolic blood pressure at seated rest 1-minute before the start of CPET 1 and 1-minute before the start of CPET 2. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Systolic blood pressure at peak effort | Systolic blood pressure at peak effort during CPET 1 and during CPET 2. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 
| Respiratory Exchange Ratio (RER) at peak effort | RER at peak effort during CPET 1 and during CPET 2. RER is calculated as the rate of carbon dioxide production divided by the rate of oxygen consumption, and during exercise is an indicator of participant effort. | During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiopulmonary exercise test (CPET), post-exertional malaise (PEM)