Cardiopulmonary Testing in ME/CFS to Improve Diagnostic Accuracy

Cardiopulmonary Exercise Testing as a Diagnostic Tool and a Quantitative Measure of Post-exertional Malaise in Myalgic Encephalopathy/Chronic Fatigue Syndrome

Circumstantial evidence suggests that patients diagnosed with myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) perform worse on day 2 in a 2-day consecutive cardiopulmonary exercise test (CPET). The aim of this study is to examine if CPET can distinguish between ME/CFS patients and healthy controls.

Study Overview

• Status: Completed
• Conditions: Chronic Fatigue Syndrome; Myalgic Encephalomyelitis
• Intervention / Treatment: Procedure: Cardiopulmonary testing

Detailed Description

Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) leads to a substantial reduction in activity level. Cardiopulmonary exercise testing (CPET) quantifies physical performance, or functional capacity, by direct measurements of the maximal oxygen uptake (VO2max). Functional capacity is the ability of an individual to perform aerobic work as defined by the VO2max, and the assessment of functional capacity reflects the ability to perform activities of daily living that require sustained aerobic metabolism.

To the best of knowledge few robustly designed studies on repeated CPET in ME/CFS are published, and they demonstrated a significant reduction in functional capacity expressed as VO2max and anaerobic threshold. This marked functional decline on the second test has apparently not been described for any other chronic, disabling conditions, and might represent a possible diagnostic tool for ME/CFS; hence the investigators will examine this. In addition they will examine other biological markers (e.g. cytokines and anti-oxidative compounds) before and after the exercise tests to test if the groups can be further distinguished.

The main aim of this study is to evaluate the use of repeated CPET as an objective diagnostic marker of ME/CFS. Specifically the investigators want to address the following questions:

I. Will patients with ME/CFS demonstrate a significant reduction in VO2max compared to healthy individuals? If such a difference can be demonstrated, is it unique for patients with ME/CFS classified according to the strictest criteria compared to others with longstanding fatigue?

II. What is the blood lactate profile before, during and after CPET?

III. Are there any correlations between the decline in VO2max and other biological variables such as markers of oxidative stress, immune dysregulation or metabolic dysfunction?

IV. Is cardiac function impaired among ME/CFS patients as assessed by ecco-cardiography?

Three groups will be included: (i) ME/CFS patients; (ii) patients with fatigue, but not MF/CFS; and (iii) healthy controls.

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• Norway
  • Hakadal, Norway
    • Glittre Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. Patients with ME/CFS
2. Patients with fatigue but not ME/CFS
3. Healthy controls

Description

Inclusion Criteria:

• Diagnosed with ME/CFS according to the Canadian and Fukuda criteria; miid to moderately affected)
• Provide written consent
• Able to perform the test

Exclusion Criteria:

• Not provided written consent
• Unable to perform the test

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ME/CFS group; Patients with a verified diagnosis of ME/CFS according to the Canada criteria	Procedure: Cardiopulmonary testing; A 2-day consecutive testing on an ergometer cycle
Fatigue group; Patients with fatigue, but not ME/CFS	Procedure: Cardiopulmonary testing; A 2-day consecutive testing on an ergometer cycle
Control group; Healthy control persons	Procedure: Cardiopulmonary testing; A 2-day consecutive testing on an ergometer cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal oxygen uptake	Measurement of oxygen uptake during ergometer cycling	At 48 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate accumulation	Regular sampling of blood for measurements of lactate	At 48 hour
Cytokine profile	Regular sampling of blood for measurements of cytokines	At 48 hour
Immunophenotyping	Regular sampling of blood for measurements of cell surface markers	At 48 hour
Cardiac status	Measurements of Cardiac function using ecco-cardiography	At 48 hour

Collaborators and Investigators

• Sponsor: University of Oslo
• Collaborators: Oslo University Hospital; The Glittre Clinic
• Investigators: Principal Investigator: Per O Iversen, MD, University of Oslo

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: November 14, 2016
• First Submitted That Met QC Criteria: November 18, 2016
• First Posted (Estimate): November 21, 2016

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: inflammation; cardiopulmonary exercise testing; oxidative status
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Pain; Neurologic Manifestations; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Central Nervous System Infections; Syndrome; Fatigue; Myalgia; Fatigue Syndrome, Chronic; Encephalomyelitis
• Other Study ID Numbers: 2012/571

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No