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

• ClinicalTrials.gov Identifier: NCT04026425
• Recruitment Status: Recruiting
• First Posted: July 19, 2019
• Last Update Posted: February 17, 2021
• Sponsor: Ithaca College
• Collaborators: Cornell University; Weill Medical College of Cornell University; Workwell Foundation
• Information provided by (Responsible Party): Ithaca College

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Myalgic Encephalomyelitis; Chronic Fatigue Syndrome	Other: Two-day cardiopulmonary exercise test	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 180 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Probing Metabolism, Circulating Inflammatory Molecules, Extracellular Vesicles and Immune Dysregulation in Individual Immune Cells in ME/CFS
• Actual Study Start Date: August 1, 2018
• Estimated Primary Completion Date: August 31, 2021
• Estimated Study Completion Date: August 31, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Volume of oxygen consumed at peak effort [ Time Frame: 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 peak effort during CPET 1 and during CPET 2.
2. Volume of oxygen consumed at ventilatory/anaerobic threshold (VAT) [ Time Frame: During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. ]
   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.
3. Rate of work performed at peak effort [ Time Frame: 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 during CPET 1 and during CPET 2. Rate of work is measured in Watts.
4. Rate of work performed at VAT [ Time Frame: 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 during CPET 1 and during CPET 2. Rate of work is measured in Watts.
5. Heart rate at peak effort [ Time Frame: 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 during CPET 1 and during CPET 2.
6. Heart rate at VAT [ Time Frame: 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 during CPET 1 and during CPET 2.
7. Systolic blood pressure at seated rest [ Time Frame: 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 1-minute before the start of CPET 1 and 1-minute before the start of CPET 2.
8. Systolic blood pressure at peak effort [ Time Frame: 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 during CPET 1 and during CPET 2.
9. Respiratory Exchange Ratio (RER) at peak effort [ Time Frame: During intervention on day 1 and during intervention on day 2; assessed through study completion, approximately 4 years from study start date. ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, California

ID Med; Recruiting

Torrance, California, United States, 90505

Contact: Jared Stevens, B.S. 209-599-7194 info@workwellfoundation.org

United States, New York

Ithaca College; Active, not recruiting

Ithaca, New York, United States, 14850

Weill Cornell Medicine; Recruiting

New York, New York, United States, 10021

Contact: Xiangling Mao, M.S. 212-746-2632 xim2004@med.cornell.edu

Sponsors and Collaborators

Ithaca College

Cornell University

Weill Medical College of Cornell University

Workwell Foundation

Investigators

• Study Director: Betsy Keller, Ph.D.; Ithaca College
• Study Director: Geoff Moore, M.D.; Ithaca College

More Information

Additional Information:

Related information 

• Responsible Party: Ithaca College
• ClinicalTrials.gov Identifier: NCT04026425
• Other Study ID Numbers: U54NS105541 ( U.S. NIH Grant/Contract ); 5U54NS105541 ( U.S. NIH Grant/Contract )
• First Posted: July 19, 2019
• Last Update Posted: February 17, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ithaca College:

cardiopulmonary exercise test (CPET); post-exertional malaise (PEM)

Additional relevant MeSH terms:

Fatigue Syndrome, Chronic; Encephalomyelitis; Virus Diseases; Muscular Diseases; Musculoskeletal Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Central Nervous System Infections