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

ISRCTN	ISRCTN54285094
DOI	https://doi.org/10.1186/ISRCTN54285094
Secondary identifying numbers	G0200434

Submission date: 22/05/2003
Registration date: 22/05/2003
Last edited: 03/11/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Prof Peter Denton White
Scientific

Department of Psychological Medicine
St Bartholomew's Hospital
London
EC1A 7BE
United Kingdom

Phone	+44 (0)20 7601 8160
Email	p.d.white@qmul.ac.uk

Study information

Study design	Multicentre randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Available on http://www.pacetrial.org/TrialInfo.pdf
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
Study acronym	PACE: Pacing, Activity, and Cognitive behaviour therapy: a randomised Evaluation
Study hypothesis	1. Are cognitive behaviour theraphy (CBT) and/or graded exercise therapy (GET) more effective than pacing in reducing both fatigue and disability? 2. Is pacing more effective than usual medical care? 3. Are there differential predictors of response to CBT and GET and does the mechanism of change differ? 4. Do different treatments have differential effects on outcomes (i.e. disability versus symptoms)? 5. What factors predict a favourable response to treatment in general and with specific treatments? 6. What are the mechanisms of change with successful treatment? 7. What are the relative cost-effectiveness and cost-utility of these treatments? As of 16/02/09 this record was updated to reflect an amendment to the anticipated end date. The initial information at the time of registration was 13/06/2009.
Ethics approval(s)	UK West Midlands Multicentre Research Ethics Committee, 31/03/2003
Condition	Symptoms and general pathology
Intervention	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.
Intervention type	Other
Primary outcome measure	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 measures	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
Overall study start date	14/06/2004
Overall study end date	01/07/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	600
Participant 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
Participant 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).
Recruitment start date	14/06/2004
Recruitment end date	28/11/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

St Bartholomew's Hospital

London
EC1A 7BE
United Kingdom

Sponsor information

Queen Mary University of London (UK)
University/education

Gerry Leonard
Mile End Road
London
E1 4NS
England
United Kingdom

"ROR"	https://ror.org/026zzn846

Funders

Funder type

Government

Medical Research Council (MRC) (UK)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

The Scottish Chief Scientist's Office (UK)

No information available

Department of Health in England and Wales (UK)

No information available

Department for Work and Pensions (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Protocol article	protocol	08/03/2007	Yes	No
Results article	results	05/03/2011	Yes	No
Results article	results	01/10/2013	Yes	No
Statistical Analysis Plan	statistical analysis plan	13/11/2013	No	No
Results article	results	01/05/2014	Yes	No
Results article	results	01/12/2015	Yes	No