Broadbent 2012

Trial name or title	Pilot study on the effects of intermittent and graded exercise compared with no exercise for optimising health and reducing symptoms in chronic fatigue syndrome (CFS) patients
Methods	Randomised controlled trial, parallel
Participants	Inclusion criteria: medical diagnosis of chronic fatigue syndrome: persistent and disabling, and/or recurring, fatigue lasting longer than 6 months, which does not result from physical exertion and is not alleviated by rest. Other symptoms include muscle weakness and pain, ongoing medical symptoms such as swollen lymph nodes and fever, poor sleep, poor concentration and reduced quality of life Exclusion criteria: diagnosed cardiac and/or respiratory disease; joint or muscle condition/disease other than CFS that is contraindicated for exercise; any mental health condition that may affect exercise participation or safety of participants and researchers Age minimum: 18 years Age maximum: 60 years Gender: both male and female
Interventions	Randomised controlled trial of intermittent exercise training compared with graded exercise and standard care. Graded exercise is the current recommended exercise approach to CFS; it consists of self‐paced (e.g. low‐intensity) steady state exercise at a constant workload for a short time; as the patient's fitness gradually improves, the length of time and eventually the intensity are increased in a gradual graded manner, provided no adverse symptoms occur. Intermittent or interval exercise consists of short blocks of exercise at low to moderate intensity with a rest interval in between bouts of exercise (e.g. 1 minute of low‐intensity cycling, followed by 1 minute of rest, followed by 1 minute of cycling); total time spent exercising can be gradually increased whilst rest or unloaded exercise intervals are maintained. Participants will be randomly allocated to 1 of 3 groups. Each group will consist of 20 participants to provide a power of 80% for the study (based on data from Gordon 2010), with an a prior test used to compute required sample size, given alpha (P value 0.05), power and effect size for an F test, and looking at ANOVA fixed effects, main effects and interactions (GPower). Volunteers will participate in 3 aerobic exercise sessions (cycling on a cycle ergometer) per week, consisting of the following. Warm‐up of 5 minutes of unloaded cycling for both ITE and GE groups Either a steady state (constant effort) low‐ to moderate‐intensity cycling period (50% VO2peak, RPE 3 Modified Borg Scale) initially for 10 minutes (GE group) OR an intermittent exercise block of 1 minute of moderate‐intensity cycling (60% VO2peak, RPE 4 to 5) alternated with 1 minute of unloaded or very low‐intensity/unloaded cycling (20% to 30% VO2peak, RPE 1 to 2), totaling 20 minutes Cool‐down of 5 minutes unloaded cycling plus stretching of main muscle groups for both groups Over the 12 weeks of the project, we aim to progress the duration of SS exercise towards 20 minutes, as tolerated by the participant, and to progress ITE participants towards intervals of 2 to 3 minutes of moderate‐intensity cycling, alternated with 1‐minute intervals of low‐intensity cycling, totaling 25 to 30 minutes in duration. All group sessions will be supervised by a member of the research team (consisting of accredited exercise physiologists) with assistance from postgraduate Masters of Clinical Exercise Physiology students, who are studying to become accredited exercise physiologists Total intervention duration will be 12 weeks for graded, intermittent and control groups
Outcomes	Improved physiological adaptations to exercise (reduced RPE, heart rate and blood pressure). Rate of perceived exertion (RPE) is assessed using a standard 10‐point Borg Scale on which participants are asked how hard they feel they are exercising; heart rate will be measured using a 12‐lead ECG during prestudy and poststudy exercise tests, and during exercise sessions, by using a Polar heart rate monitor; blood pressure will be monitored constantly during prestudy and poststudy exercise testing, and during exercise sessions, using a standard sphygmomanometer and an adult‐sized cuff and stethoscope Increased lymphocyte function and reduced inflammatory cytokines measured prestudy and poststudy by comparison of immune cell counts, lymphocyte (CD4, CD8, CD19, NK) function and inflammatory cytokines (IFN‐λ, IL‐1) in both exercise groups and control groups. Cell counts will be measured by full blood count (standard pathology); lymphocyte subsets will be measured by cell count using a FACSCanto flow cytometer (Becton Dickinson); lymphocyte function will be analysed using proliferative assays with flow cytometric fluorescent analysis; and inflammatory cytokines will be assessed using standard ELISA assays Increased VO2peak, as measured prestudy and poststudy by open circuit spirometry (Sensormedics) metabolic cart and by breath‐by‐breath analysis. The test protocol is a cycle test starting with a 3‐minute warm‐up of unloaded cycling, followed by 1‐minute increments of 10 watts (W) until a VO2 plateau is achieved (i.e. VO2 does not increase, although workload continues to increase and/or RER > 1.15 and/or peak heart rate within 10 beats per minute of age‐predicted maximum and/or volitional exhaustion). The test may also be stopped at the request of participants if they feel too fatigued. If a submaximal value is achieved at this stage, a peak VO2 value can be extrapolated by using a linear regression Reduced fatigue and symptoms (Cummins Fatigue Scale)
Starting date	10/02/2013
Contact information	suzanne.broadbent@scu.edu.au
Notes	http://apps.who.int/trialsearch/Trial.aspx?TrialID=ACTRN12612001241820 http://www.anzctr.org.au/ACTRN12612001241820.aspx