Condition category
Digestive System
Date applied
30/10/2017
Date assigned
03/11/2017
Last edited
06/08/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Crohn’s disease is a type of inflammatory bowel disease (IBD) that can affect any part of the intestine. The severity of Crohn’s disease varies a lot between different people, and this means that what might be the best treatment for one person may not be appropriate for someone else. This study will see whether a simple blood test (‘biomarker’) can improve Crohn’s disease outcomes and reduce the number of flares experienced by enabling delivery of ‘personalised therapy’ (that is, treatment tailored to the individual person based on their predicted disease course and severity). All patients enrolled receive established treatments (there are no new drug therapies being trialed – rather, it is the new blood ‘biomarker’ that is being tested). The aim of this study is to see if the biomarker allows us to choose the right strategy for the right patient at diagnosis, and so improve short-term and long-term outcomes.

Who can participate?
Adults aged 16 to 80 who have been diagnosed with Crohn’s disease diagnosed within three months.

What does the study involve?
All participants receive established treatments (there are no new drug therapies being trialed rather, it is the new blood ‘biomarker’ that is being tested). Participants are randomly allocated to one of two groups. Those in the first group are treated with a course of 8 infusions of Infliximab (“Top-Down”) over the first year together with an additional tablet-based treatment (immunomodulator). This is currently the most effective treatment in Crohn’s disease and is usually reserved for patients who have developed severe disease. Those in the second group follow the usual standard of care (“Step-Up”), which may include infliximab if the disease flares recurrently. Participants are assessed to see if the biomarker helps improve their symptoms.

What are the possible benefits and risks of participating?
It is expected that participants willl experience relief in their symptoms or an improvement in their disease, as all participants will be receiving active treatment (there are no placebos / dummy drugs being used). There are no notable risks with participating.

Where is the study run from?
This study is being run by the Cambridge Clinical Trials Unit and takes place in hospitals in the UK.

When is the study starting and how long is it expected to run for?
June 2014 to March 2022

Who is funding the study?
Wellcome Trust (UK)

Who is the main contact?
Mr Francis Dowling
francis.dowling@addenbrookes.nhs.uk

Trial website

http://www.crohnsprofiletrial.com

Contact information

Type

Scientific

Primary contact

Mr Francis Dowling

ORCID ID

Contact details

Cambridge Clinical Trials Unit
Cambridge University Hospitals NHS Foundation Trust
Addenbrooke's Hospital
Coton House Level 6
Flat 61
Box 401
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 254 666
francis.dowling@addenbrookes.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

35971

Study information

Scientific title

PRedicting Outcomes For Crohn’s dIsease using a moLecular biomarkEr (PROFILE) trial

Acronym

PROFILE

Study hypothesis

This study aims to demonstrate that a new 'biomarker' test will allow patients with Crohn's disease to the receive the most appropriate treatment from the time of diagnosis.

Ethics approval

East of England – Cambridge South REC, 02/11/2017, ref: 17/EE/0382

Study design

Randomised; Interventional; Design type: Prevention, Other

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Medical condition: Crohn’s disease.
Specialty: Gastroenterology, Primary sub-specialty: Gastroenterology.
UKCRC code/ Disease: Oral and Gastrointestinal/ Other diseases of the digestive system

Intervention

This trial aims to test the prognostic capabilities of a new biomarker. Participants with Crohn’s disease are stratified using a biomarker, then randomised to receive either ‘Top down’ or ‘Step up’ treatment. All participants are given a course of steroids at their screening visit to ensure no participants is without suitable medication prior to being randomised.

Step up therapy is in line with current standard practice. If patients experience a disease flare following the course of steroids provided at screening, a second course will prescribed. If patients are still not suitably maintained participants continue on to Anti-TNF therapy (Infliximab infusions).

Top down therapy requires participants to start on Anti TNF therapy (Infliximab infusions) two weeks after their baseline/randomisation visit until week 48.

All patients are in the trial and followed up for 48 weeks.

Intervention type

Other

Phase

Phase IV

Drug names

Primary outcome measure

1. Sustained surgery free remission is measured using questionnaires from steroid induction treatment (screening) through weeks 4, 16, 32 and 48.
2. Steroid free remission is measured using questionnaires from steroid induction treatment (screening) through weeks 4, 16, 32 and 48.

The primary outcomes are measured using the sustained surgery and steroid free remission from completion of steroid induction treatment through to week 48 based upon information we collected at each trial time point.

Secondary outcome measures

1. Mucosal healing is measured using local and central reading of colonoscopy and MRE from baseline to week 48.
2. Quality of life is measured using the IBDQ questionnaire from screening through weeks 16, 32 and 48.
3. Quality of life is measured using the EuroQol questionnaire from screening through weeks 16, 32 and 48.
4. Quality of life is measured using the IBDQ questionnaire from screening through weeks 16, 32 and 48.
5. Health resource usage is measured using the resource usage questionnaire from screening through weeks 16, 32 and 48.

Secondary outcomes are measured using the local and central reading of colonoscopy/MRE over 1 year and the quality of life assessment (IBDQ) provided over the duration of the study and the patient rated resource usage / quality of life assessment (EuroQol) questionnaires provided over the duration of the study.

Overall trial start date

01/06/2014

Overall trial end date

01/03/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Crohn’s disease diagnosed within 3 months* using standard endoscopic, histologic or radiological criteria
2. Clinical evidence of active Crohn’s disease (corresponding to an HBI > 7)
3. Endoscopic evidence of at least moderately active Crohn’s disease (corresponding to an SES-CD > 6 or > 4 if limited to terminal ileum)
4. CRP > upper limit of normal on local assay OR Calprotectin > 200 μg/g
5. Immunomodulator and anti-TNFα naïve
6. Aged 16-80 years old

* Patients that have glucocorticoids in this period need to have discontinued this medication prior to screening assessments and still have active disease.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 400; UK Sample Size: 400

Participant exclusion criteria

1. Patients with ulcerative colitis or indeterminate colitis
2. Patients with fistulating peri-anal Crohn’s disease or active perianal sepsis
3. Patients with obstructive symptoms AND evidence of a fixed stricture on radiology or colonoscopy, which suggest that the subject is at high risk of requiring surgery over the following year. N.B. patients with modest degrees of stricturing on imaging but no obstructive symptoms may be included according to clinician judgement
4. Patients with contra-indications to study medications including a history of hepatitis B or C, tuberculosis
5. Patients with a history of malignancy
6. Patients who are pregnant or breastfeeding at screening
7. Other serious medical or psychiatric illness currently on going, or experienced in the last 3 months, that could compromise the study
8. Patients unable to comply with protocol requirements (for reasons including alcohol and/or recreational drug abuse)

Recruitment start date

01/12/2017

Recruitment end date

28/02/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Barts and Royal London Hospital
The Royal London Hospital Whitechapel Road Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Bedford Hospital
Kempston Road
Bedford
MK42 9DJ
United Kingdom

Trial participating centre

Darlington Memorial Hospital
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom

Trial participating centre

Derriford Hospital, Plymouth
Derriford Road Crownhill
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Epsom General Hospital
Dorking Road
Epsom
KT18 7EG
United Kingdom

Trial participating centre

Glasgow Royal Infirmary
84 Castle Street
Glasgow
G4 0SF
United Kingdom

Trial participating centre

New Victoria Hospital, Glasgow
52 Grange Road
Glasgow
G42 9LF
United Kingdom

Trial participating centre

Gloucestershire Royal Hospital
Great Western Road Gloucestershire
Gloucester
GL1 3NN
United Kingdom

Trial participating centre

Guy's and St Thomas' Hospital
Westminster Bridge Road Lambeth
London
SE1 7EH
United Kingdom

Trial participating centre

Hull Royal Infirmary
Hull and East Yorkshire Hospitals NHS Trust Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

James Paget Hospital, Great Yarmouth
Lowestoft Road Gorleston-on-Sea
Great Yarmouth
NR31 6LA
United Kingdom

Trial participating centre

John Radcliffe Hospital
Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Lincoln County Hospital
Greetwell Road
Lincoln
LN2 5QY
United Kingdom

Trial participating centre

Luton & Dunstable University Hospital
Lewsey Road
Luton
LU4 0DZ
United Kingdom

Trial participating centre

Musgrove Park Hospital, Taunton
Parkfield Drive
Taunton
TA1 5DA
United Kingdom

Trial participating centre

New Queen Elizabeth Hospital Birmingham
Mindelsohn Way Edgbaston
Birmingham
B15 2GW
United Kingdom

Trial participating centre

Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Trial participating centre

Norfolk and Norwich Hospital
Colney Lane
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Royal Blackburn Hospital
Haslingden Road
Blackburn
BB2 3HH
United Kingdom

Trial participating centre

Royal Bournemouth Hospital
Castle Lane E
Bournemouth
BH7 7DW
United Kingdom

Trial participating centre

Royal Devon and Exeter Hospital, Wonford
Barrack Road
Exeter
EX2 5DW
United Kingdom

Trial participating centre

Royal Hampshire County Hospital
Romsey Road
Winchester
SO22 5DG
United Kingdom

Trial participating centre

Royal Liverpool Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Barry Building Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Royal Victoria Infirmary, Newcastle
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

Royal Wolverhampton NHS Trust
West Midlands
WV10 0QP
United Kingdom

Trial participating centre

Russells Hall Hospital
Pesnett Road
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

St George's Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom

Trial participating centre

St Mark's Hospital
Watford Road Middlesex
Harrow
HA1 3UJ
United Kingdom

Trial participating centre

St Mary's Hospital, London
Praed Street
London
W2 1NY
United Kingdom

Trial participating centre

The Cumberland Infirmary
Newtown Road
Carlisle
CA2 7HY
United Kingdom

Trial participating centre

Torbay Hospital
Newton Road
Torquay
TQ2 7AA
United Kingdom

Trial participating centre

University College Hospital
235 Euston Road Bloomsbury
London
NW1 2BU
United Kingdom

Trial participating centre

University Hospital of Wales, Cardiff
Heath Park Way
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Watford General Hospital
Vicarage Road
Watford
WD18 0HB
United Kingdom

Trial participating centre

Western General Hospital
Crewe Rd S
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Wythenshawe Hospital
Southmoor Road Wythenshawe
Manchester
M23 9LT
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Wellcome Trust

Alternative name(s)

Wellcome

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal in 2020.

IPD sharing statement:
The data sharing plans for the trial are currently unknown and will be made available at a later date.

Intention to publish date

31/12/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

06/08/2018: The recruitment end date was changed from 28/02/2019 to 28/02/2020. 21/06/2018: Trial website added.