PROFILE - personalised medicine in Crohn's disease
| ISRCTN | ISRCTN11808228 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11808228 |
| Secondary identifying numbers | 35971 |
- Submission date
- 30/10/2017
- Registration date
- 03/11/2017
- Last edited
- 14/03/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
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 February 2023
Who is funding the study?
Wellcome Trust (UK)
Who is the main contact?
Mr Francis Dowling
francis.dowling@nhs.net
Contact information
Scientific
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
| Phone | +44 (0)1223 254 666 |
|---|---|
| francis.dowling@nhs.net |
Study information
| Study design | Randomised; Interventional; Design type: Prevention, Other |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN11808228_PIS_V2_20Oct17.pdf |
| Scientific title | PRedicting Outcomes For Crohn’s dIsease using a moLecular biomarkEr (PROFILE) trial |
| Study 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(s) | East of England – Cambridge South REC, 02/11/2017, ref: 17/EE/0382 |
| Condition | Crohn’s disease |
| 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 |
| 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 study start date | 01/06/2014 |
| Overall study end date | 01/02/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 400; UK Sample Size: 400 |
| Total final enrolment | 390 |
| 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 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 | 15/12/2021 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Cambridge
CB2 0QQ
United Kingdom
Whitechapel Road
Whitechapel
London
E1 1BB
United Kingdom
Bedford
MK42 9DJ
United Kingdom
Darlington
DL3 6HX
United Kingdom
Crownhill
Plymouth
PL6 8DH
United Kingdom
Epsom
KT18 7EG
United Kingdom
Glasgow
G4 0SF
United Kingdom
Glasgow
G42 9LF
United Kingdom
Gloucestershire
Gloucester
GL1 3NN
United Kingdom
Lambeth
London
SE1 7EH
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Gorleston-on-Sea
Great Yarmouth
NR31 6LA
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Lincoln
LN2 5QY
United Kingdom
Luton
LU4 0DZ
United Kingdom
Taunton
TA1 5DA
United Kingdom
Edgbaston
Birmingham
B15 2GW
United Kingdom
DD1 9SY
United Kingdom
Norwich
NR4 7UY
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Blackburn
BB2 3HH
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
Exeter
EX2 5DW
United Kingdom
Winchester
SO22 5DG
United Kingdom
Liverpool
L7 8XP
United Kingdom
Eastern Road
Brighton
BN2 5BE
United Kingdom
Newcastle upon Tyne
NE1 4LP
United Kingdom
WV10 0QP
United Kingdom
Dudley
DY1 2HQ
United Kingdom
Southampton
SO16 6YD
United Kingdom
London
SW17 0QT
United Kingdom
Middlesex
Harrow
HA1 3UJ
United Kingdom
London
W2 1NY
United Kingdom
Carlisle
CA2 7HY
United Kingdom
Torquay
TQ2 7AA
United Kingdom
Bloomsbury
London
NW1 2BU
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Watford
WD18 0HB
United Kingdom
Edinburgh
EH4 2XU
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
Sponsor information
Hospital/treatment centre
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Charity
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 15/06/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal in 2020. |
| IPD sharing plan | The data sharing plans for the trial are currently unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version V2 | 20/10/2017 | 03/11/2017 | No | Yes |
| Protocol article | protocol | 05/12/2018 | 04/11/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 21/02/2024 | 26/02/2024 | Yes | No | |
| Statistical Analysis Plan | version 3 | 17/08/2023 | 14/03/2024 | No | No |
Additional files
- ISRCTN11808228_PIS_V2_20Oct17.pdf
- Uploaded 03/11/2017
- ISRCTN11808228 Profile Trial SAP v3 17AUG2023.pdf
Editorial Notes
14/03/2024: The statistical analysis plan was uploaded as an additional file.
26/02/2024: Publication reference added.
30/06/2023: The following changes have been made:
1. A study contact was updated.
2. The overall study end date was changed from 15/12/2022 to 01/02/2023 and the plain English summary was changed to reflect the update.
22/03/2022: The final enrolment number has been added.
02/03/2021: The following changes have been made:
1. The recruitment end date has been changed from 28/02/2021 to 15/12/2021.
2. The overall trial end date has been changed from 01/03/2022 to 15/12/2022.
3. The intention to publish date has been changed from 31/12/2020 to 15/06/2023.
4. The plain English summary has been updated to reflect the changes above.
19/03/2020: The recruitment end date was changed from 28/02/2020 to 28/02/2021.
04/11/2019: Publication reference added.
03/04/2019: The condition has been changed from "Medical condition: Crohn’s disease. Specialty: Gastroenterology, Primary sub-specialty: Gastroenterology. UKCRC code/ Disease: Oral and Gastrointestinal/ Other diseases of the digestive system" to "Crohn’s disease" following a request from the NIHR.
06/08/2018: The recruitment end date was changed from 28/02/2019 to 28/02/2020.
21/06/2018: Trial website added.
