Condition category
Mental and Behavioural Disorders
Date applied
22/05/2003
Date assigned
22/05/2003
Last edited
24/04/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Peter Denton White

ORCID ID

Contact details

Department of Psychological Medicine
St Bartholomew’s Hospital
London
EC1A 7BE
United Kingdom
+44 (0)20 7601 8160
p.d.white@qmul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

G0200434

Study information

Scientific title

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

UK West Midlands Multicentre Research Ethics Committee gave approval on 31 March 2003

Study design

Multicentre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Available on http://www.pacetrial.org/TrialInfo.pdf

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

Phase

Not Applicable

Drug names

Primary outcome measures

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 trial start date

14/06/2004

Overall trial end date

01/07/2011

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

600, last patient recruited 28/11/2008

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

01/07/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Psychological Medicine
London
EC1A 7BE
United Kingdom

Sponsor information

Organisation

Queen Mary University of London (UK)

Sponsor details

Gerry Leonard
Mile End Road
London
E1 4NS
United Kingdom
+44 (0)20 7882 5555

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

The Scottish Chief Scientist's Office (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Department of Health in England and Wales (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Department for Work and Pensions (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2007 protocol in http://www.ncbi.nlm.nih.gov/pubmed/17397525
2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21334061
2013 statistical analysis plan in http://www.ncbi.nlm.nih.gov/pubmed/24225069
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23363640

Publication citations

  1. Results

    White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O'Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M, , Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial., Lancet, 2011, 377, 9768, 823-836, doi: 10.1016/S0140-6736(11)60096-2.

  2. Statistical analysis plan

    Walwyn R, Potts L, McCrone P, Johnson AL, DeCesare JC, Baber H, Goldsmith K, Sharpe M, Chalder T, White PD, A randomised trial of adaptive pacing therapy, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome (PACE): statistical analysis plan., Trials, 2013, 14, 386, doi: 10.1186/1745-6215-14-386.

  3. Results

    White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M, Recovery from chronic fatigue syndrome after treatments given in the PACE trial., Psychol Med, 2013, 43, 10, 2227-2235, doi: 10.1017/S0033291713000020.

  4. White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R, , Protocol for the PACE trial: 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., BMC Neurol, 2007, 7, 6, doi: 10.1186/1471-2377-7-6.

Additional files

Editorial Notes