Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000299303p
Ethics application status
Not yet submitted
Date submitted
2/02/2017
Date registered
27/02/2017
Date last updated
27/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The temporal relationship of the effects of repeated exercise on physiological variables in individuals with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)
Scientific title
The temporal relationship of the effects of repeated exercise on physiological variables in individuals with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME
Secondary ID [1] 291048 0
None
Universal Trial Number (UTN)
U1111-1192-3682
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Fatigue Syndrome 301839 0
Myalgic Encephalomyelitis 301862 0
Condition category
Condition code
Inflammatory and Immune System 301518 301518 0 0
Other inflammatory or immune system disorders
Other 301542 301542 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pre-exercise measures: All individuals will undergo endothelial function assessment by pulse wave velocity and analysis (via SphygmaCor). Individuals will then provide a 20ml venous blood sample (cytokine assessment). Following this, individuals will have their resting blood pressure, height and weight recorded and heart rate variability measured. Individuals will then undertake neuropsychological testing via the stroop, trail, substitution and choice tests to test their pre exercise cognitive function.

Exercise testing: A validated incremental cycle ergometer exercise test designed to peak at work rates in 8-12 minutes. Participants will maintain 60-80 rpm throughout the test and will be encouraged to participate for as long as possible. The workload will be increased at a rate of 5 watts/20 second. Breath by breath gas samples will be collected throughout the exercise test via metabolic cart. Participants will then remain seated on the cycle ergometer and monitored for 2-5 minutes for recovery. Heart rate and rating of perceived exertion will be measured during each minute of the test and blood pressure manually every two minutes. Following a 20-minute period of rest, cardiac output will be measured through a non-invasive rebreathing technique and will require participants to cycle for up to five minutes at a set resistance at their respiratory exchange ratio.

Post-exercise measures: Exercise recovery questionnaire as used by Davenport et al., 2010 will be completed. This allows participants to report symptoms following their exercise test, until complete recovery. We will record symptoms of fatigue each 24 hours for 7 days.
48 or 72 hours later - Individuals will repeat all tests after either 48 or 72 hours.
Intervention code [1] 297037 0
Diagnosis / Prognosis
Comparator / control treatment
Each of the Chronic Fatigue Syndrome patients will be age, gender and fitness matched to healthy controls who will have no known diseases.
Each of the healthy controls will also be tested at either 48 hours or 72 hours, but will be age and gender matched to the CFS/ME randomised into each group.
Control group
Active

Outcomes
Primary outcome [1] 300928 0
Peak oxygen consumption will be assessed with a maximal exercise test whereby online breath by breath information will be recorded with a metabolic cart
Timepoint [1] 300928 0
baseline, 48 hours or 72 hours
Primary outcome [2] 300929 0
cognitive function will be assessed via computerised tasks using the STROOP colour-word, Trail, and substitution cognitive function tests
Timepoint [2] 300929 0
baseline, 48 and 72 hours
Primary outcome [3] 301083 0
arterial stiffness will be assessed via ultrasound.
Timepoint [3] 301083 0
baseline, 48 and 72 hours
Secondary outcome [1] 331227 0
Cardiac output will be assessed using the Defares non-invasive rebreathing method (35% Oxygen, 4% Carbon dioxide and balance nitrogen)
Timepoint [1] 331227 0
Baseline, 48, and 72 hours
Secondary outcome [2] 331685 0
cytokines will be measured from blood samples taken. Cytokines to be assessed include (IL) 1B, IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL17.
Timepoint [2] 331685 0
baseline, 48 and 72 hours
Secondary outcome [3] 331686 0
lactate metabolism will be measured using pin pricks to the fingers and using lactate strips and a lactate pro machine. Lactate will be measured every 2 minutes during the incremental exercise test.
Timepoint [3] 331686 0
baseline, 48 and 72 hours
Secondary outcome [4] 331816 0
carbon dioxide production will be assessed with a maximal exercise test whereby online breath by breath information will be recorded with a metabolic cart
Timepoint [4] 331816 0
48 and 72 hours
Secondary outcome [5] 331817 0
anaerobic threshold will be analysed using the v slope method from the data collected during the breath by breath measurement from the online gas measurements.
Timepoint [5] 331817 0
48, 72 hours
Secondary outcome [6] 331818 0
Heart rate will be measured using a polar heart rate monitor during the exercise test
Timepoint [6] 331818 0
48 and 72 hour
Secondary outcome [7] 331819 0
power output will be measured via a lode bike which will measure peak power output in Watts
Timepoint [7] 331819 0
48 and 72 hours
Secondary outcome [8] 331820 0
Blood pressure will be measured manually both at rest and every three minutes during the exercise test using a stethescope and sphygmanomoter
Timepoint [8] 331820 0
48 and 72 hours.

Eligibility
Key inclusion criteria
CFS/ME individuals will need to meet the International Consensus Criteria, Canadian Criteria and Fukuda case definition. These involve 3 major inclusion points, >6 months of severe fatigue, significant reductions in day to day functionality and the presence of 4 out of 8 major symptoms.
Healthy volunteers will be age, gender and fitness match and will be free from disease.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Depressive disorders, individuals who have a known disease unrelated to Chronic Fatigue Syndrome/ME.
Healthy volunteers will be free from disease.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size for the study is based on our previous study where the most important variables were oxygen consumption (ml/kg/min) and work rate (W). An anova model was used to calculate the sample size where group A (CFS/ME) mean VO2 was 23.55 ml/kg/min, and group B (healthy controls) 23.55 ml/kg/min, with standard deviation of 4.31 for group a and 8.99 for group b. With a power of 80%, the sample size is calculated at 54. When using work rate as a variable using the same method calculated the sample size as 36. Therefore i would suggest that this study aims to recruit 60 volunteers to account for drop outs and to ensure that the power of the study is good.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2017
Actual
Date of last participant enrolment
Anticipated
1/09/2017
Actual
Date of last data collection
Anticipated
30/09/2017
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment outside Australia
Country [1] 8614 0
New Zealand
State/province [1] 8614 0
Bay of Plenty

Funding & Sponsors
Funding source category [1] 295489 0
University
Name [1] 295489 0
Massey University Research Fund
Country [1] 295489 0
New Zealand
Primary sponsor type
University
Name
Massey University
Address
Research and Development Office
Private bag 11-222
Palmerston North
4442
Country
New Zealand
Secondary sponsor category [1] 294309 0
None
Name [1] 294309 0
Address [1] 294309 0
Country [1] 294309 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 296817 0
Ethics committee address [1] 296817 0
Ethics committee country [1] 296817 0
Date submitted for ethics approval [1] 296817 0
28/02/2017
Approval date [1] 296817 0
Ethics approval number [1] 296817 0

Summary
Brief summary
Provide innovative information on the temporal relationship of physiological responses (oxygen consumption, carbon dioxide production, anaerobic threshold, cardiac output, heart rate, power output, and blood pressure), inflammation and cognitive functioning in CFS/ME patients following repeated cardiopulmonary exercise testing at 48 and 72 hours.

Design: Randomised controlled trial with CFS/ME randomised to either 48 or 72 hour repeat testing and age matched healthy controls.
Recruitment: Participants will be recruited through the national organisation (ANZMES) via flyers and mail out to patients as well as identified through a database of existing CFS/ME from previous studies. Upon making contact and showing interest potential participants complete the online De Paul Symptom Questionnaire. This will be analysed to ensure participants meet the CFS International, Canadian and Fukuda criteria for diagnosis of CFS.

Participants: 60 participants will be recruited, 30 CFS/ME, and 30 matched healthy controls will be recruited. Testing will take place in Massey University's Exercise and Sport Science mobile lab. Individuals will be matched with control subjects for age, body mass and activity levels and will be free from non-communicable diseases. All participants will give written informed consent.

Pre-exercise measures: All individuals will undergo endothelial function assessment by pulse wave velocity and analysis (via SphygmaCor). Individuals will then provide a 20ml venous blood sample (cytokine assessment). Following this, individuals will have their resting blood pressure, height and weight recorded and heart rate variability measured. Individuals will then undertake neuropsychological testing via the stroop, trail, substitution and choice tests to test their pre exercise cognitive function.

Exercise testing: A validated incremental cycle ergometer exercise test designed to peak at work rates in 8-12 minutes. Participants will maintain 60-80 rpm throughout the test and will be encouraged to participate for as long as possible. The workload will be increased at a rate of 5 watts/20 second. Breath by breath gas samples will be collected throughout the exercise test via metabolic cart. Participants will then remain seated on the cycle ergometer and monitored for 2-5 minutes for recovery. Heart rate and rating of perceived exertion will be measured during each minute of the test and blood pressure manually every two minutes. Following a 20-minute period of rest, cardiac output will be measured through a non-invasive rebreathing technique and will require participants to cycle for up to five minutes at a set resistance at their respiratory exchange ratio.

Post-exercise measures: Exercise recovery questionnaire as used by Davenport et al., 2010 will be completed. This allows participants to report symptoms following their exercise test, until complete recovery. We will record symptoms of fatigue each 24 hours for 7 days
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72118 0
Dr Lynette Hodges
Address 72118 0
School of Sport and Exercise
College Health
Massey University
Private Bag 11-222
Palmerston North
4442
Country 72118 0
New Zealand
Phone 72118 0
+64 6 3569099
Fax 72118 0
Email 72118 0
[email protected]
Contact person for public queries
Name 72119 0
Dr Lynette Hodges
Address 72119 0
School of Sport and Exercise
College Health
Massey University
Private Bag 11-222
Palmerston North
4442
Country 72119 0
New Zealand
Phone 72119 0
+64 6 356 9099
Fax 72119 0
Email 72119 0
[email protected]
Contact person for scientific queries
Name 72120 0
Dr Lynette Hodges
Address 72120 0
School of Sport and Exercise
College Health
Massey University
Private Bag 11-222
Palmerston North
4442
Country 72120 0
New Zealand
Phone 72120 0
+ 64 6 3569099
Fax 72120 0
Email 72120 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.