A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy

• Register: ISRCTN
• Last refreshed on: 17 October 2016
• Main ID: ISRCTN54285094
• Date of registration: 22/05/2003
• Prospective Registration: Yes
• Primary sponsor: Queen Mary University of London (UK)
• Public title: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy
• Scientific title: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy
• Date of first enrolment: 14/06/2004
• Target sample size: 600
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN54285094
• Study type: Interventional
• Study design: Multicentre randomised controlled trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

United Kingdom

Contacts

• Name: Peter Denton White

Key inclusion & exclusion criteria

Inclusion criteria: Consent:
1. Both participant and clinician agree that randomisation is acceptable
2. The participant has given written informed consent

Eligibility:
3. The participant meets operationalised Oxford research diagnostic criteria for CFS
4. The participant's Chalder Fatigue Questionnaire score is 6 or more
5. The participant's SF-36 physical function sub-scale score is 65 or less (changed from '60 or less' in April 2006)
6. The participant will be aged at least 18 years old, either sex
Exclusion criteria: 1. All potential participants will be screened for medical exclusions, by history and physical examination. Appropriate investigations will be undertaken by either the referring doctor or the centre doctors (checked by the RN). Patients with a relevant alternative medical diagnosis will be excluded. Investigations will be those recommended by the Royal Colleges' Report on CFS/ME and the CMO's working group report. These results will be collated by the RN, and will have been undertaken within six months of the baseline assessment.
2. The Research Nurse (RN) will use a standardised psychiatric interview (the Structured Clinical Interview for DSM-IV - SCID), under supervision by a participating centre PI or nominated deputy, to exclude those who are at significant risk of self-harm and those with psychiatric exclusions listed in the Oxford diagnostic criteria for CFS.
3. Patients who are considered by the RN in discussion with their centre leader to be unable to do one or more of the trial therapies or to complete all trial measures or for whom participation in the PACE trial would be inappropriate to their clinical needs (e.g. someone with significant post traumatic stress disorder or borderline personality disorder).
4. Patients who have previously received one of the trial treatments before from a centre participating in PACE (rather than any secondary care clinic for Chronic Fatigue Syndrome) and received a course of any of the supplementary therapies of CBT, GET or pacing therapy from a therapist will be excluded from taking part in the trial, or of advice from a PACE doctor that is judged to have been similar to SSMC (changed from 'Patients who have previously attended a specialist fatigue clinic and received a course of any of the supplementary therapies of CBT, GET or pacing therapy from a therapist will be excluded from taking part in the trial' in April 2006).

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Symptoms and general pathology
Mental and Behavioural Disorders
Chronic fatigue syndrome (CFS)

Intervention(s)

PACE is a multicentre randomised controlled trial. The group assignment is parallel group.
1. Standardised Specialist Medical Care alone (SSMC) - manual guided advice from a secondary care clinic specialist in chronic fatigue
2. Standardised Specialist Medical Care plus adaptive pacing therapy (APT)
3. Standardised Specialist Medical Care plus graded exercise therapy (GET)
4. Standardised Specialist Medical Care plus cognitive behaviour therapy (CBT)
There is no masking as the supplementary treatments being trialled are delivered by therapists and maintaining any blind would be very difficult. Even though treatment allocation is not blinded, staff are encouraged not to discuss randomisations or any subject that might inadvertently lead to bias.

Primary Outcome(s)

1. Is APT and SSMC more effective than SSMC alone in reducing (i) fatigue, (ii) disability, or (iii) both?
2. Is CBT and SSMC more effective than APT and SSMC in reducing (i) fatigue, (ii) disability or (iii) both?
3. Is GET and SSMC more effective than APT and SSMC in reducing (i) fatigue, (ii) disability, or (iii) both?
4. Are the active rehabilitation therapies (of either CBT or GET) more effective than the adaptive approach of APT when each is added to SSMC, in reducing fatigue, in reducing physical disability?
5. What are the relative cost-effectiveness and cost-utility of these treatments?

Secondary Outcome(s)

The secondary analyses are exploratory but we will be guided by previously published findings.
1. Do different treatments have differential effects on outcomes (i.e. fatigue versus physical disability)?
2. What baseline factors (other than randomised treatment) predict a reduction in (i) fatigue, (ii) disability in all participants?
3. Are there differential predictors of response to APT, CBT, GET, and SSMC (i.e. treatment-covariate interactions)?
4. Are there changes in factors (time-dependent covariates) during the earlier stages of treatment that (after controlling for baseline overall and differential predictors) are associated with outcome at 1 year from randomisation?
5. Are the differences across treatment groups in the primary outcomes associated with similar differences in secondary outcomes (e.g. in global change, mood, quality of life and objective measures of physical activity)?

Hypotheses of efficacy:
1. APT plus SSMC is more effective than SSMC alone in reducing (i) fatigue, (ii) reducing physical disability and in reducing (iii) both
2. CBT plus SSMC is more effective than APT and SSMC in reducing (i) fatigue, (ii) disability and in reducing (iii) both
3. GET plus SSMC is more effective than APT and SSMC in reducing (i) fatigue, (ii) disability and in reducing (iii) both
4. The active rehabilitation therapies (of either CBT or GET) are more effective than the adaptive approach of APT when each is added to SSMC, in reducing fatigue, in reducing physical disability and both
5. CBT plus SSMC is more effective than SSMC in reducing (i) fatigue, (ii) disability and in reducing (iii) both
6. GET plus SSMC is more effective than SSMC in reducing (i) fatigue, (ii) disability and in reducing (iii) both

Secondary ID(s)

G0200434

Source(s) of Monetary Support

Medical Research Council (MRC) (UK), The Scottish Chief Scientist's Office (UK), Department of Health in England and Wales (UK), Department for Work and Pensions (UK)