Clinical trial NCT03675087: Assessment of Exercise Response in Chronic Fatigue Syndrome / Myalgic Encephalomyelitis.
Official title: Assessment of Exercise Response in Chronic Fatigue Syndrome / Myalgic Encephalomyelitis.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fatigue Syndrome, Chronic
Keywords: Work Capacity Evaluation
Fatigue Syndrome,Chronic
Exercise Tests
Lead sponsor: Escuela Universitaria de Fisioterapia de la Once
Sponsor class: OTHER
Collaborators: name: Hospital Universitario La Paz
First posted: 2018-09-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis affected and derived by their specialist in internal medicine from Hospital Universitario La Paz or by the Asociación de Afectados por el Síndrome de Fatiga Crónica y el Síndrome de Sensibilidad Química Múltiple de la Comunidad de Madrid, to the Escuela Universitaria de Fisioterapia de la ONCE and to the Department of Functional Tests of the Pneumology Service of the Hospital Universitario La Paz, Madrid (Spain) from October 1st, 2018 to July 1st, 2025 and that fulfill the inclusion criteria and do not present any exclusion criteria.

Brief summary: This study evaluates the correlation between the 6-min walking test (6MWT) with gases measurement, and the peak cardiopulmonary exercise testing (CPET) using incremental cycling with gases and workload measurement, in order to determine if the 6MWT detects impairment in exercise tolerance and if it avoids the post-exertional malaise that the peak CPET causes on decreasing levels of physical activity, in participants affected by chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME).

Physical activity level at baseline (usual activity, the parcipant will not be given any directions) will be recorded during 7 days, 24 hours/day. Afterwards, the 6MWT will be performed. After this test, the physical activity level will be collected again during 7 days, 24 hours/day. Peak CPET will be carried out 14 days after 6MWT to make sure that the basal levels are recovered, and finally, physical activity level will be collected again during 7 days, 24 hours/day.

Detailed description: Chronic fatigue syndrome/ myalgic encephalomyelitis presents with a significant deterioration of functional capacity, which seriously affects the quality of life. The peak or maximal incremental CPET is considered valid for the evaluation of exercise tolerance of those affected by CFS/ME, but its performance causes worsening of its symptomatology, decreasing its physical activity level after the test. It has not been verified whether the 6MWT (submaximal exercise test) with gases measurement is able to assess the exercise tolerance of those affected by SFC/EM without increasing their symptoms. So far, only the correlation between another submaximal test and a peak CPET in two different groups of participants have been analyzed and proven, which it makes necessary to check adequately whether there is a correlation by performing both tests on the same participants. In addition, it is necessary to compare the degree of worsening in physical activity level that both tests produce in participants, because they have not been objectively evaluated in any previous study. It could be useful to have a more innocuous and simple test for the assessment of exercise tolerance in CFS/ME in clinical practice, in order to evaluate the benefits of treatments like rehabilitation programs. 6MWT could respond to these characteristics because it reaches an identical value in peak VO2 than in the peak CPET in other pathologies and it generates less physical stress.

This research will be developed with the utmost respect for individual human rights, according to the postulates accepted internationally by the United Nations and the European Commission (Helsinki Act of 1964 and the Oviedo Convention of 1997) and Regulation (EU) 2016/679 of the European Parliament and the Council of April 27, 2016 on Data Protection (RGPD).

Participation in this study is entirely voluntary and does not imply any risk to health. Participants are entitled to refuse to participate or to leave the study at any time they choose.

All information will be treated confidentially. If it is decided to publish the results of the study, in these publications will not include individual data or the names of the participants, only information considered globally will be included.

This study has been approved in August 2018 by the Ethics and Research Committee of the La Paz University Hospital in Madrid (HULP Code: PI-3320).

The sample sizes were calculated in order to find the significance of the Pearson linear correlation coefficient between two variables, for a unilateral hypothesis test according to the formula: n = \[Z1-α + Z1- β / ½ ln (1 + r / 1-r)\]\^2 + 3 and the largest has been chosen, which involve studying 22 participants.

Taking into account the data of a previous study with participants of similar characteristics, a correlation of the parameters that set up the primary outcome, peak VO2 of r = 0.7 is assumed.

An expected drop out in rate of 0.474 has been estimated from the data obtained in another related study.

Accepting an alpha risk of 0.05 and a beta risk of 0.20 in a unilateral contrast, 22 participants are required to detect a positive correlation between the variables of the exercise tests, equal to or greater than those found in the study used as reference.

This size will guarantee sufficient power to detect correlation in the purpose of the study. To guarantee this power, and since there is not enough information about the previous values, an intermediate analysis of the data, will be carried out in the middle of the study to recalculate the size of the final sample.

The incidental sampling will be carried out according to a non-probabilistic system of consecutive cases of people diagnosed with CFS/ME.

Data analysis / Statistical methods:

1. Descriptive: Descriptive analysis of all variables collected will be carried out. For quantitative data, centralization and dispersion measures will be calculated according to the distribution of each variable, such as mean, standard deviation, minimum and maximum median. The qualitative data will be described by absolute frequency and percentage. It will be checked if the variables are distributed normally by means of the Kolmogórov-Smirnov test for a single sample.
2. Correlation: A bivariate analysis will be performed to observe the association between the variables obtained in the 6MWT with gases measurement and those of the peak incremental CPET; between peak VO2 in the peak CPET and the distance achieved during the 6MWT; between peak VO2 and physical activity level at baseline and after each test; and between distance achieved in the 6MWT and physical activity level at baseline and after each test. In case of normality, the Pearson product-moment correlation coefficient will be used, and if any variable is not distributed normally, the Spearman correlation analysis will be used.
3. Linear regression: If some variables of the 6MWT are strongly correlated with the corresponding variables of the peak incremental CPET, a linear regression analysis will be performed to construct a regression equation for the prediction of the peak test performance. If necessary, a multiple linear regression analysis will be carried out to control the possible confounding variables: medication intake, time of disease evolution, quality of life, multidimensional fatigue, physical activity level at baseline, age, sex, profession, weight, height and body mass index.
4. Comparison: a comparative analysis of physical activity level at baseline and physical activity levels after each of the tests and between physical activity levels after each of the tests to compare decrease in physical activity level that generate both tests; using repeated measures ANOVA for related samples, if they meet the normal distribution or, if not, the Friedman test.

In case of drop out, the data collected will be taken into account for the analysis.

The analysis will assume a confidence level (1 - α) of 0.95 (significance level α = 0.05). The program SPSS® Statistics version 20.0 (SPSS Incorporation, Chicago, USA) will be used.

Eligibility criteria: Inclusion Criteria:

* To be diagnosed by a medical specialist in internal medicine with experience in this disease. For this, the participant must fulfill with the diagnostic criteria of CFS/ME, following the recommended criteria for the diagnosis of 2015.
* Prior signing of the informed consent.

Exclusion Criteria:

* Present any of the diagnoses considered excluding of the CFS/ME, according to the international criteria recommended for clinical diagnosis and the selection of subjects for research:

  * Primary psychiatric disorders
  * Somatoform disorders
  * or Substance abuse
* Present any of the absolute or relative contraindications, to perform exercise tests, described in previous investigations:

  * Decompensated heart failure
  * Acute myocardial infarction (less than 3 days)
  * Syncope
  * Unstable angina
  * Cardiac arrhythmia poorly controlled
  * Endocarditis, myocarditis or acute pericarditis
  * Acute pulmonary edema
  * Moderate or severe cardiac valvular stenosis
  * Suspected dissection or dissecting aortic aneurysm
  * O2 saturation at rest less than 85%
  * Acute renal failure
  * Untreated thyrotoxicosis
  * Acute infection
  * Uncontrolled hypertension (greater than 200-120 mmHg)
  * Hypertrophic obstructive cardiomyopathy
  * High-grade atrioventricular block
  * Significant pulmonary arterial hypertension
  * Advanced or risky pregnancy
  * Significant diselectrolithmia
  * Severe symptomatic aortic stenosis
  * Severe anemia
  * Pulmonary embolism
  * Acute thrombophlebitis
  * Traumatologic, orthopedic or neurological pathology that does not allow to walk or cycling.
  * Psychic incapacity to understand the instructions of the tests.
  * Present comorbidity of Multiple Chemical Sensitivity Syndrome.
  * Have performed the peak incremental CPET in the last 3 years.

Primary outcomes:
measure: Mean Value of the Peak VO2 in both Exercise Tests (6MWT and Peak CPET) in Milillitres/ Minute.
timeFrame: 3 hours one day and 2 hours another day.
Secondary outcomes:
measure: Mean Age of Participants in Years.
timeFrame: 5 minutes.
measure: Percentage of Males and Females.
timeFrame: 5 minutes.
measure: Percentage of Participants´ Professions.
timeFrame: 5 minutes.
measure: Mean of Time of Evolution of the Disease in Years.
timeFrame: 5 minutes.
measure: Percentage of Participants with Autonomic Dysfunction.
timeFrame: 5 minutes.
measure: Percentage of Medications Intake.
timeFrame: 10 minutes.
measure: Mean of Weight in Kilograms.
timeFrame: 5 minutes.
measure: Mean of Height in Meters.
timeFrame: 5 minutes.
measure: Mean of Body Mass Index in Kilograms/ Meters^2.
timeFrame: 5 minutes.
measure: Mean of Physical Activity Level at Baseline on ActivPAL 4 Micro.
timeFrame: 7 days.
measure: Mean Forced Vital Capacity (FVC) on Forced Spirometry in Milillitres.
timeFrame: 15 minutes.
measure: Mean Forced Expiratory Volume in the First Second (FEV1) on Forced Spirometry in Milillitres.
timeFrame: 15 minutes.
measure: Mean Tiffeneau Index (FEV1 / FVC) on Forced Spirometry in Percentage.
timeFrame: 15 minutes.
measure: Mean Change from Baseline in Medications Dosage at After Both Exercise Tests (6MWT and Peak CPET).
timeFrame: 10 minutes on day and 10 minutes another day.
measure: Mean Change from Baseline in Quality of Life Related to Health on SF-36v2 at After Both Exercise Tests.
timeFrame: 20 minutes one day and 20 minutes another day.
measure: Mean Change from Baseline in Multidimensional Fatigue on MIF:S at After Both Exercise Tests.
timeFrame: 10 minutes one day and 10 minutes another day.
measure: Mean Change from Baseline in Physical Activity Level on ActivPAL 4 Micro at After each of the Exercise Tests.
timeFrame: 21 days, in 3 periods of 7 days.
measure: Mean Value of the Peak VO2 Body Weight Adjusted in 6MWT and in Peak CPET in Milillitres/ Kilograms/ Minute.
timeFrame: 3 hours one day and 2 hours another day.
measure: Percentage of Exercise Tolerance.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Distance on the 6MWT in Metres.
timeFrame: 3 hours.
measure: Mean Peak Work Load on the Peak CPET in Watts.
timeFrame: 2 hours.
measure: Mean Change from Baseline in O2 Saturation on Spirometer at After each of the Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in Heart Rate on Pulsiometer or Electrocardiogram at Maximum Hearth Rate in both Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in Heart Rate on Pulsiometer or Elecrocardiogram at After each of the Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in Blood Pressure on Tensiometer at After each of the Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in Total Heart Rate Variability on Pulsiometer or Electrocardiogram at After each of the Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean of the Maximum Heart Rate in Percentage.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in VO2 on Spirometer at the Peak VO2 of the 6MWT and the Peak CPET.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in VO2 Body Weight Adjusted on Spirometer at the Peak VO2 of both Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in Oxygen Pulse on Spirometer at the Peak VO2 of both Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in CO2 Production on Spirometer at the Peak VO2 of both Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in Respiratory Exchange Ratio (RER) at the Peak VO2 of both Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
measure: Mean Change from Baseline in Minute Ventilation at the Peak VO2 of both Exercise Tests.
timeFrame: 3 hours one day and 2 hours another day.
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Escuela Universitaria de Fisioterapia de la ONCE
Study officials:
affiliation: Escuela Universitaria de Fisioterapia de la Once
name: Ana B Varas-de-la-Fuente, Chair
role: STUDY_CHAIR
affiliation: Escuela Universitaria de Fisioterapia de la Once
name: Susana García-Juez
role: PRINCIPAL_INVESTIGATOR
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