Journal: BMC Neurology 2007, 7:6. Published online March 8 2007. [Note: Readers may access a pdf file of the entire 34-page trial protocol online at http://www.biomedcentral.com/1471-2377/7/6 ]
Authors and affiliation: White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R. PACE trial group. [E-Mail: Peter D. White, email@example.com ]
Background: Chronic Fatigue Syndrome (CFS, also called Myalgic Encephalomyelitis/Encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioral therapy, and graded exercise therapy.
The latter two therapies [behavioral therapy and graded exercise therapy] have been found to be efficacious in small trials, but patient organizations’ surveys have reported adverse effects.
Although pacing has been advocated by patient organizations, it lacks empirical support. Specialist medical care is commonly provided, but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone.
Methods/Design: 600 patients, who meet operationalized diagnostic criteria for CFS, will be recruited from secondary care into a randomized trial of four treatments, stratified by current co-morbid depressive episode and different CFS/ME criteria. The four treatments are standardized specialist medical care either given alone or with adaptive pacing therapy or cognitive behavior therapy or graded exercise therapy. Supplementary therapies will involve 14 sessions over 23 weeks and a ‘booster session’ at 36 weeks.
Outcome will be assessed at 12, 24, and 52 weeks after randomization.
Two primary outcomes of self rated fatigue and physical function will assess differential effects of each treatment on these measures.
Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility.
The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures.
Discussion: The results of the trial will provide information about:
The benefits and adverse effects of these treatments,
Their cost-effectiveness and cost-utility,
The process of clinical improvement,
And the predictors of efficacy.