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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Fatigue Syndrome; Myalgic Encephalomyelitis
• Intervention / Treatment: Other: Two-day cardiopulmonary exercise test

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90505
      • ID Med
  • New York
    • Ithaca, New York, United States, 14850
      • Ithaca College
    • New York, New York, United States, 10021
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ME/CFS; Adults with ME/CFS	Other: Two-day cardiopulmonary exercise test; 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.
Active Comparator: Healthy controls; Healthy, low-active adults	Other: Two-day cardiopulmonary exercise test; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Ithaca College
• Collaborators: Weill Medical College of Cornell University; Cornell University; Workwell Foundation
• Investigators: Study Director: Betsy Keller, Ph.D., Ithaca College; Study Director: Geoff Moore, M.D., Ithaca College

Publications and helpful links

Helpful Links

• Related information

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): March 15, 2022
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: cardiopulmonary exercise test (CPET); post-exertional malaise (PEM)
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Central Nervous System Infections; Neuroinflammatory Diseases; Fatigue Syndrome, Chronic; Encephalomyelitis
• Other Study ID Numbers: U54NS105541 (U.S. NIH Grant/Contract); 5U54NS105541 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No