Randomised controlled trial of graded exercise in chronic fatigue syndrome, 2004, Wallman et al

Randomised controlled trial of graded exercise in chronic fatigue syndrome
Karen E Wallman, Alan R Morton, Carmel Goodman, Robert Grove and Andrew M Guilfoyle
Med J Aust 2004; 180 (9): 444-448. || doi: 10.5694/j.1326-5377.2004.tb06019.x
Published online: 3 May 2004

Abstract
Objective: To investigate whether 12 weeks of graded exercise with pacing would improve specific physiological, psychological and cognitive functions in people with chronic fatigue syndrome (CFS).

Design: Randomised controlled trial.

Setting: Human performance laboratory at the University of Western Australia.

Participants: 61 patients aged between 16 and 74 years diagnosed with CFS.

Interventions: Either graded exercise with pacing (32 patients) or relaxation/flexibility therapy (29 patients) performed twice a day over 12 weeks.

Main outcome measures: Changes in any of the physiological, psychological or cognitive variables assessed.

Results: Following the graded exercise intervention, scores were improved for resting systolic blood pressure (P = 0.018), work capacity (W·kg-1) (P = 0.019), net blood lactate production (P = 0.036), depression (P = 0.027) and performance on a modified Stroop Colour Word test (P = 0.029). Rating of perceived exertion scores, associated with an exercise test, was lower after graded exercise (P = 0.013). No such changes were observed in the relaxation/flexibility condition, which served as an attention-placebo control.

Conclusions: Graded exercise was associated with improvements in physical work capacity, as well as in specific psychological and cognitive variables. Improvements may be associated with the abandonment of avoidance behaviours.

 

I have posted this old study because it's referred to in another thread
Investigating the relationship between physical activity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Franklin, 2021

The problem raised by that thesis was quoted by @ME/CFS Skeptic:

Rather than diverting that thread, I decided to take a closer look at the Wallman paper, particularly because it's used in the Cochrane review.

 

Here are the fatigue scores:
Mental fatigue
GET group: Before 6.3 (5.6–7.0) After 4.5 (3.9–5.2)
Relaxation group: Before 5.6 (5.0–6.1) After 4.8 (4.2–5.5)
p = 0.023
Physical fatigue
GET group: Before: 11.6 (10.1–13.0) After: 8.1 (6.9–9.4)
Relaxation group: Before: 11.4 (10.4–12.3) After: 9.6 (8.3–10.9)
p = 0.074

So adding mental and physical fatigue:

GET group Before: 6.3+11.6= 17.9 After: 4.5+8.1 = 12.6
Reduction in combined fatigue score: 17.9-12.6 = 5.3
Relaxation group Before: 5.6+11.4 = 17.0 After: 4.8+9.6= 14.4
Reduction in combined fatigue score: 17.0-14.4 = 2.6

By taking the fatigue scores after GET, they get a between group difference of 1.8
But there was already a between group difference in the other direction of 0.9 at the start of the trial, so surely the between group reduction in fatigue score is the relevant figure. Calculating it two ways, we get 5.3-2.6=2.7, or 0.9+1.8=2.7

The key finding, if anything can be concluded from these scores, is that it was only mental fatigue not physical fatigue that was reduced significantly in the exercise group compared with the relaxation group.

 

However, the thing that stands out for me most in this trial is the description of GET, which is actually HR and symptom contingent pacing, as far as I can see. Here's the description of their version of GET:

Graded exercise program

Note that there is no mention of increasing exercise, or increasing duration of exercise, and any 'grading' seems to be cutting back to a level that doesn't provoke PEM. In fact they even call it 'pacing'.

Yet this study was apparently included in the Cochrane review.
I need to go and have a look.

 

From the discussion:

This improved ability to do more work may be because the exercise regimen was not associated with any relapse. This may have resulted in the abandonment of the commonly held belief by CFS sufferers that exercise results in the exacerbation of symptoms, which consequently leads to the avoidance of exercise.29,30 Additionally, graded exercise was associated with a reduction in perceived effort scores associated with the exercise test. Many studies have documented that CFS subjects report a greater sense of effort associated with exercise tests compared with control subjects.9,31,32 Gibson et al9 suggest that an abnormal sense of effort in CFS may be the result of the resetting of a sensory threshold in response to the initial onset of symptoms, and that this then becomes a learned response. Results from our study suggest that 12 weeks of graded exercise intervention may have resulted in a further resetting of this sensory threshold toward more normal values. Of importance is the implication that this reduced sense of effort may be associated with everyday work tasks that require similar work capacities.

 

This is the description of the GET from this study from the Cochrane review:
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003200.pub8/full

Wallman 2004

 

Possibly why they had to do the PACE trial cos this one wasn’t sufficiently hard core

 

And anything using Oxford is worse.