The PACE trial; A RCT of CBT, graded exercise, adaptive pacing and usual medical care for the chronic fatigue syndrome

Chronic fatigue syndrome (CFS, also known as ME) affects 1 in 50 people. The main symptom is severe disabling fatigue made worse by activity. Its cause is unknown and we do not know how best to treat it
Treatments that may help include: specialist medical care alone (SMC) and SMC supplemented with one of the following special therapies: adaptive pacing therapy (APT); cognitive behaviour therapy (CBT); graded exercise therapy (GET).
SMC comprises medical follow up visits, self-help advice and drug treatment of symptoms
APT involves learning to balance activity and rest.
CBT helps patients to understand and cope better with the illness.
GET involves gradually increasing physical activity.
The trial will compare these treatments in 600 patients with CFS/ME, who will be followed up for a year. The aim is to see which treatments are best in reducing fatigue and enabling patients to do more. We will also look to see whether they have harmful effects and find out how they work.
The results of the trial will allow patients, doctors and health service planners to choose the best, safest and most cost –effective treatment for CFS/ME.

The chronic fatigue syndrome (CFS, sometimes called ME) is a debilitating medically unexplained condition which has a prevalence of between 0.5% and 2% in the population of the UK. It has major effects on the health and welfare of both patients and their families. Two treatments that have shown promise for CFS are cognitive behaviour therapy (CBT) and graded exercise therapy (GET). However the evidence for these therapies is based on small trials, and surveys have suggested that they may make some patients worse. We do not know either how they work or who responds best to each treatment. Patient organisations routinely recommend a different approach of adaptive pacing therapy (APT) that is popular, but lacks empirical support. APT is based on the theory that sufferers have a fixed amount of available energy. The recent report to the CMO on the management of CFS was unable to recommend one of these treatments above the others. There is therefore a need for a trial which compares therapies, seeks evidence of adverse effects, and also examines predictors and mechanisms of response. The proposed trial will compare the efficacy, adverse effects, and cost-effectiveness of adding CBT, GET, or APT to usual medical care and compare them to the control treatment of usual medical care alone.
We will recruit 600 subjects who meet operationalised criteria for CFS, from six hospital clinics, into a single blind randomised controlled trial of the four treatments. Fourteen sessions of each of the three specific therapies will be given over five months and those recieving UMC alone will be put on a waiting list for their choice of therapy. Outcome will be assessed up to one year after entry. The two primary outcomes of self-rated fatigue and impairment of physical function, will allow us to assess differential effects of treatment on fatigue and function. Secondary outcomes will include other subjective measures of symptoms, mood, and function and objective measures of physical activity and fitness, as well as cost.
The results will inform health services about the efficacy and cost-effectiveness of these treatments for CFS. A better understanding the mechanism of successful treatment will provide a basis for the rational development of more efficient therapies. Knowledge of predictors will allow health professionals to match treatments to individual patients. Finally, it will provide information to patients and patients organisations about the benefits and adverse effects of available treatments for CFS.