Eating Behaviour in Crohn's Disease
Conditions: Crohn's Disease
Sponsor: University of Nottingham

 
 
 
Page 1 of 23 
 
Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
 
 
 
 
 
 
Eating behaviour in Crohn's disease 
Final Version 1.0 
19 February 2015  
 
 
 
Short title:  
 
Eating behaviour in Crohn’s disease 
 
 
IRAS Project ID: 
171270 
 
 
Study Sponsor:  
University of Nottingham 
 
 
Sponsor reference: 
15005 
 
 
Funding Source: 
Nottingham Digestive Diseases Biomedical 
Research Unit  
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
STUDY PERSONNEL AND CONTACT DETAILS 
 
Sponsor: 
University of Nottingham 
Contact name 
Ms Angela Shone 
 
Head of Research Governance 
 
Research and Graduate Services 
 
King’s Meadow Campus 
 
Lenton Lane 
 
Nottingham 
 
NG7 2NR 
 
Chief investigator:  
Dr Gordon William Moran 
   
Clinical Associate Professor of Gastroenterology 
         
NIHR Nottingham Digestive Diseases Biomedical 
Research Unit 
 
D1405, West Block, D Floor, Queen’s Medical 
Centre, Nottingham University Hospitals, NG7 2UH 
 
Phone: 0115 (82) 30461 
 
 
 
Fax: 0115 (82) 31409  
 
 
Email: gordon.moran@nottingham.ac.uk  
 
 
Co-investigators:   
       
Dr Graham Finlayson 
Associate Professor Institute of Psychological 
Sciences 
Institute of Psychological Sciences 
University of Leeds 
Telephone +44(0)113 343 7601 
Work Email g.s.finlayson@leeds.ac.uk 
 
Dr Richard Anthony Wardle  
Rotational Foundation Year 1 Doctor 
Royal Derby Hospital  
Uttoxeter New Rd 
Derby  
DE22 3NE 
Telephone 01332 340131 
Work Email richardwardle@nhs.net  
 
 
 
 
 
 
 
 
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Study Statistician: 
Alyshah Abdul Sultan 
 
Division of Epidemiology and Public Health 
 
City Hospital Campus, University of Nottingham 
 
Room B126 Clinical Science Building 2 
 
Hucknall Road, Nottingham 
 
NG5 1PB 
 
Work Email: 
alyshah_abdul_sultan@nottingham.ac.uk  
  
 
 
 
 
 
 
 
 
 
 
Study Coordinating Centre:  NIHR Nottingham Digestive Disease Centre 
Biomedical Research Unit, E Floor, West Block, 
 
Queen’s Medical Centre, Nottingham University 
Hospitals, NG7 2UH 
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
SYNOPSIS 
 
Title 
Eating behaviour in Crohn's disease 
Short title 
Eating behaviour in Crohn's disease 
Chief Investigator 
Dr Gordon Moran 
Objectives 
The primary objective is to quantify food intake in Crohn’s disease (CD) 
patients with active disease and compare it to healthy volunteers. 
Measures of food intake will be repeated in these patients when in 
remission.  
The secondary objectives of this study is to quantify changes in appetite 
and eating behaviour in patients with active CD and compare these to 
those in HV and inactive CD as measured by the appetite-related 
questionnaires 
Study Configuration 
Qualitative questionnaire based study  
Setting 
A tertiary setting 
Sample size estimate 
Due to the exploratory nature of this study and lack of previous data, we 
feel the sample size suggested is achievable and will be sufficient to 
provide robust statistics and 95% confidence intervals. This work will 
provide pilot data to further power downstream work.  
 
Number of participants 
Crohns: n = 60 
Healthy volunteers: n = 60 
Participants will be age-, gender- and BMI-matched. 
Eligibility criteria 
Patients: 
We will study a cohort of CD patients (aged 16-75yrs) with active disease 
as defined by:  
• 
CD activity index (CDAI) of 220-450 or,   
• 
faecal calprotectin of >250µg/g and  
• 
one of the following: ileocolonoscopy, CT or MR enterography 
showing active inflammatory uncomplicated disease of the ileum 
(B1L1 or B1L3 phenotype).  
• 
Stable doses of immunosuppressive agents or anti-TNF agents 
will be permitted. 
• 
Body mass index (BMI) of 18-30.  
 
 
Healthy Volunteers Controls 
• 
Aged 16-75yrs old (age, weight and sex-matched). 
 
Description of 
interventions 
CD and Healthy volunteer (HV) control group 
 
1. Measure of food intake through three telephone-administered 24-
h dietary recalls 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
2. Eating behaviour traits will be measured through self-reported 
measures: Three Factor Eating Questionnaire (TFEQ) Restraint, 
Disinhibition and Hunger subscales; the Binge Eating Scale; the 
Power of Food Scale; the Dutch eating behaviour questionnaire 
and the Control of Eating Questionnaire  
 
Duration of study 
Study Duration: 24 months  
Each participant will be in the study for 1 week. (Participants restudied 
back when in  remission will be within the study for a maximum of 12 
months of initial recruitment).  
 
Methods of analysis  
Differences in food intake (measured as mean total 24 hr kcal intake) and 
eating behaviour traits between the three groups (active CD, inactive CD 
and HV) will be carried out with an analysis of variance with a post-hoc 
Bonferroni correction. To identify potential mechanistic links between 
mean food intake and eating behaviour, these data will be correlated to 
measures of disease activity (CRP and faecal calprotectin). Data will be 
presented as mean. P<0.05 will be considered as significant. 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
ABBREVIATIONS  
 
 
 
AE 
 
Adverse Event 
ANOVA 
Analysis of Variance 
ASL 
 
Arterial Spin Labelling 
BOLD  
Blood-oxygen level-dependant  
CD 
 
Crohn’s Disease 
CI 
 
Chief Investigator overall 
CNS   
Central Nervous System 
CRF 
 
Case Report Form 
DAP 
 
Data Analysis Plan  
DMC  
Data Monitoring Committee  
EC 
 
Enteroendocrine Cells  
GCP 
 
Good Clinical Practice 
GM 
 
Grey Matter 
HV 
 
Healthy Volunteer  
IBD 
 
Inflammatory Bowel Disease  
ICF 
 
Informed Consent Form  
NDDBRU 
Nottingham Digestive Diseases Biomedical Research Unit 
NHS 
 
National Health Service 
P/GIS  
Parent / Guardian Information Sheet 
PI 
 
Principal Investigator at a local centre 
PIS 
 
Participant Information Sheet 
REC 
 
Research Ethics Committee 
R&D 
 
Research and Development department 
RFX   
Random effects group analysis 
ROI 
 
Region of Interest 
SAE 
 
Serious Adverse Event 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
SPMMRC 
Sir Peter Mansfield Magnetic Resonance Centre 
 
SPM 
 
Statistical Parametric Mapping 
 
TMG  
Trial Management Group 
 
TSC  
Trial Steering Committee 
 
UoN 
 
University of NottinghaM 
VAS 
 
Visual analogue scores 
 
VBM 
 
Voxel-based Morphometry 
 
 
 
 
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
TABLE OF CONTENTS 
STUDY PERSONNEL AND CONTACT DETAILS ............................................................ 2 
SYNOPSIS ................................................................................................................................. 4 
ABBREVIATIONS ................................................................................................................... 6 
STUDY BACKGROUND INFORMATION AND RATIONALE ..................................... 10 
STUDY OBJECTIVES AND PURPOSE ............................................................................. 10 
PURPOSE 
10 
PRIMARY OBJECTIVE 
11 
SECONDARY OBJECTIVES 
11 
STUDY DESIGN .................................................................................................................... 11 
STUDY CONFIGURATION 
11 
RANDOMIZATION AND BLINDING 
11 
Maintenance of randomisation codes and procedures for breaking code 
12 
STUDY MANAGEMENT 
12 
DURATION OF THE STUDY AND PARTICIPANT INVOLVEMENT 
12 
End of the Study 
12 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
12 
Recruitment 
12 
Eligibility criteria 
13 
Inclusion criteria 
13 
Exclusion criteria 
13 
Expected duration of participant participation 
13 
Participant Withdrawal 
14 
Informed consent 
14 
STUDY REGIMEN 
14 
Compliance 
15 
Criteria for terminating the study 
15 
STATISTICS/ ANALYSES ................................................................................................... 15 
Methods 
15 
Sample size and justification 
15 
ADVERSE EVENTS .............................................................................................................. 16 
ETHICAL AND REGULATORY ASPECTS ..................................................................... 16 
ETHICS COMMITTEE AND REGULATORY APPROVALS 
16 
INFORMED CONSENT AND PARTICIPANT INFORMATION 
16 
RECORDS 
17 
Case Report Forms 
17 
Source documents 
17 
Direct access to source data / documents 
17 
DATA PROTECTION 
17 
QUALITY ASSURANCE & AUDIT .................................................................................... 18 
INSURANCE AND INDEMNITY 
18 
STUDY CONDUCT 
18 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
STUDY DATA 
18 
RECORD RETENTION AND ARCHIVING 
18 
DISCONTINUATION OF THE STUDY BY THE SPONSOR 
19 
STATEMENT OF CONFIDENTIALITY 
19 
PUBLICATION AND DISSEMINATION POLICY .......................................................... 19 
USER AND PUBLIC INVOLVEMENT .............................................................................. 19 
STUDY FINANCES ............................................................................................................... 20 
Funding source 
20 
Participant stipends and payments 
20 
SIGNATURE PAGES ............................................................................................................ 21 
REFERENCES ....................................................................................................................... 22 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
STUDY BACKGROUND INFORMATION AND RATIONALE 
 
Crohn’s disease (CD) patients can present with a variety of luminal and extra-luminal 
symptoms but nutritional abnormalities are a very common but poorly studied1 problem in 
this disease2. Apart from disease burden and repeated surgery, reduced appetite3 and 
associated symptoms such as nausea undoubtedly contribute, with a major impact on 
quality of life.  
Appetite and satiation, the processes by which a meal is terminated, involve complex 
interactions of homeostatic and hedonic factors. While the hypothalamus is central in the 
homeostatic control of food intake, other neural circuits integrate environmental and 
emotional cues to constitute the hedonic drive of appetite regulation. The homeostatic 
control of food intake is governed by the enteroendocrine-gut brain axis. Enteroendocrine 
cells (EC) play a pivotal role in orchestrating physiological functions in the gastrointestinal 
(GI) tract. Sensing the nutrient content of the lumen, they secrete multiple peptides and 
amines that control gut secretory and motor functions. Gut hormones act on vagal afferents 
in the GI tract, directly relaying to key central nervous system (CNS) nuclei that interface 
within the hypothalamus and other cortical areas to regulate food intake. CD patients with 
active small bowel inflammation show significant up-regulation of EC cells with an increase 
in ileal expression of chromogranin A4, 5, glucagon-like peptide-1 (GLP-1)4, key transcription 
factors in the stem cell to EC differentiation pathway4 , plasma polypeptide YY (PYY)3, 
cholecystokinin (CCK)6 levels and a reduction in the key enzyme dipeptidyl peptidase-4 
expression7. This increase in plasma peptide levels is associated with the symptoms of 
nausea and anorexia, with both symptoms, and tissue and plasma EC-peptide expression 
decreasing to normality in remission3.  
An increase in EC expression at the tissue and plasma level might affect appetite regulation 
through an increase in CNS signalling.  
Fatty-acids infused in the gut, lead to a CCK-dependent increase in CNS activity in areas 
related to homeostatic control of feeding such as the brainstem, the pons, hypothalamus, 
cerebellum and the motor cortical areas8. Glucose has been shown to decrease the 
response in the upper hypothalamus9, possibly via a GLP-1-mediated pathway10. Ghrelin 
and PYY have known homeostatic CNS signalling properties but play a hedonic role in the 
control of food intake11. In effect, the increase in plasma PYY and GLP-1 seen after Roux-
en-Y gastric bypass surgery in obese subjects or after parenteral administration12  is 
associated with a lower activation in brain-hedonic food responses and a healthier eating 
behaviour13. In CD, we expect a subdued reward value of food, but postulate that this would 
be aversive, and inappropriately impairing appetite and food intake. 
We hypothesize that in CD and small bowel inflammation we will observe a change in eating 
behaviour with loss of hedonic drives and food reward responses and an accentuated 
homeostatic response. 
 
 
STUDY OBJECTIVES AND PURPOSE 
 
PURPOSE 
The overall purpose of the study is to quantify food intake in patients with active Crohn’s 
disease and compare it to when they are in remission and to healthy age, BMI and gender-
matched healthy cohort of volunteers. We will quantify eating behaviour traits in the same 
patient cohort when in active disease and repeat when in remission. These data will be 
compared to that of healthy volunteers.  
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
PRIMARY OBJECTIVE 
The primary objective is to quantify food intake in patients with active CD and compare this to 
HV.  
 
SECONDARY OBJECTIVES 
The secondary objectives of this study are to a) quantify food intake in patients with active CD 
and compare that when in inactive disease. b) quantify changes in appetite and eating 
behaviour in patients with active CD and compare these to those in HV and inactive CD as 
measured by the appetite-related questionnaires  
 
STUDY DESIGN 
 
STUDY CONFIGURATION 
This is an open label study design. 
Primary endpoint 
The primary endpoints for this study will be food intake as measured by three telephone-
administered 24-h dietary recalls. 
 
Secondary endpoint 
The secondary endpoints for this study will be a) eating behaviour traits as measured through 
self-reported measures: Three Factor Eating Questionnaire (TFEQ) Restraint, Disinhibition 
and Hunger subscales; the Binge Eating Scale; the Power of Food Scale; the Dutch eating 
behaviour questionnaire; and the Control of Eating Questionnaire.  
 
Safety endpoints 
None of the endpoints in this study are safety endpoints.  
 
Stopping rules and discontinuation 
These studies deal with patients with active CD. We are planning a set of studies to be carried 
out when they experience an active disease flare as measured by a set of inclusion criteria. 
Usually such patients at this point are symptomatic due to their inflammatory disease. An 
increase or change in their anti-inflammatory treatment will be postponed till after the 
investigative research studies will be have been completed.  
 
To minimise any patient risk: 
a) We aim to complete all studies within a 1 week period 
b) Patients will be allowed to exit the study at any point 
c) They will have an IBD helpline accessible to them at all times. 
 
Clinical discretion will be exercised at all times. If a patient is deemed too sick to be recruited 
or too sick to continue the study once recruited: we will institute the appropriate medical 
treatment immediately and they will be promptly excluded from their study. 
 
RANDOMIZATION AND BLINDING 
There is randomisation or blinding needed for this study.  

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
Maintenance of randomisation codes and procedures for breaking code 
N/A 
 
STUDY MANAGEMENT 
The Chief Investigator has overall responsibility for the study and shall oversee all study 
management. 
 
The data custodian will be the Chief Investigator. 
 
DURATION OF THE STUDY AND PARTICIPANT INVOLVEMENT 
Study Duration: The study will last for 24 months 
 
Participant Duration: Healthy volunteer participants will be included in this study for 1 week. 
CD  participants will be included in the study until they are re-assessed in remission. A time 
limit of 12 months will be given.  
 
End of the Study 
This will be the last visit of the last study participant or the receipt of the last questionnaire from 
the last participant whichever is the later.  
 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
Recruitment 
The CI is a specialist in Inflammatory Bowel disease and also an associate professor of 
gastroenterology at the University of Nottingham and Nottingham University Hospital which 
is a tertiary-level care academic institution covering a population of approximately 1 million 
people for secondary-level care and 4.5 million people for tertiary-level care. Collectively we 
manage approximately 4000 IBD patients.  
 
Participants shall be recruited from two sources:  
 
1. CD patients from clinic.  
Members of the study team will be primarily recruiting patients with active Crohn’s 
disease from clinical practice. These participants can have a screening visit to give 
written consent in clinic. If they are unable to consent in clinic, they will be invited 
back to the Nottingham Digestive Diseases Biomedical Research Unit (NDDBRU) at 
University of Nottingham for a screening visit to give written consent.  This will be 
done primarily by the CI and his colleagues. Potential Participants will be identified 
through their medical records and at their standard clinic appointments. There is an 
existing collaborative network with the endoscopy, radiology and paediatric 
departments to enhance recruitment. Moreover there are 5 IBD nurses who are 
existing members of the research team that are key in identifying possible study 
recruits. 
 
2. CD patients and HV via the study flyer and social media. 
Our study flyer with relevant contact details, will be placed throughout Nottingham 
University Hospitals and University of Nottingham campuses, in local press, in 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
departmental Facebook and Twitter posts and in any departmental mailing/ emailing 
lists to people who have agreed to be contacted with such information. 
After making contact with the study team, prospective participants will be offered the 
invitation letter along with the patient information sheet. If agreeable to take part in 
the study they will be invited to the NDDBRU for a screening visit to obtain written 
consent by the study team.  
 
It will be explained to all participants that entry into the trial is entirely voluntary and that their 
treatment and care (in the case of CD patients) will not be affected by their decision. It will also 
be explained that they can withdraw at any time but attempts will be made to avoid this 
occurrence. In the event of their withdrawal it will be explained that their data collected so far 
cannot be erased and we will seek consent to use the data in the final analyses where 
appropriate. 
 
Eligibility criteria 
 
Please see below: 
Inclusion criteria 
We will study a cohort of CD patients with active disease as defined by:  
1. 
Age 16-75 years 
2. 
CD activity index (CDAI) of 220-450 or,   
3. 
faecal calprotectin of >250µg/g and  
4. 
one of the following: ileocolonoscopy, CT or MR enterography showing active 
inflammatory uncomplicated disease of the ileum (B1L1 or B1L3 phenotype).  
5. 
Stable doses of immunosuppressive agents or anti-TNF agents will be permitted. 
6. 
Body mass index (BMI) of 18-30.  
For HV participants, inclusion criteria’s 1 and 6 apply.  
 
Exclusion criteria 
1. 
Present or recent (within 12 weeks) corticosteroid usage 
2. 
Malignant disease  
3. 
BMI <18 or >30.  
4. 
Significant cardiovascular or respiratory disease  
5. 
Diabetes mellitus  
6. 
Current Infection  
7. 
Neurological or cognitive impairment; significant physical disability  
8. 
Significant hepatic disease or renal failure  
9. 
Abnormal blood results other than those explained by CD including bleeding diatheses 
(apart from in the case of HV where all unexplained blood results are an exclusion criteria) 
,  
10. Subjects currently participating in (or in the last three months) any other research project 
11. pregnancy or breastfeeding or 
12. Severe CD where a delay in a change in medical treatment for 1 weeks would not be 
clinically advisable 
For HV participants, all exclusion criteria apply with the exception of criteria no.12 
 
Expected duration of participant participation 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Healthy volunteer participants will be included in this study for 1 week. CD  participants will be 
included in the study until they are re-assessed in remission. A time limit of 1 year will be given.  
 
Participant Withdrawal  
Participants may be withdrawn from the trial either at their own request or at the discretion of 
the Investigator (in case deemed too unwell from their CD). The participants will be made 
aware that this will not affect their future care. Participants will be made aware (via the 
information sheet and consent form) that should they withdraw the data collected to date 
cannot be erased and may still be used in the final analysis. 
 
Informed consent 
All participants will provide written informed consent. The Informed Consent Form will be 
signed and dated by the participant before they enter the trial. The Investigator will explain the 
details of the trial and provide a Participant Information Sheet, ensuring that the participant has 
sufficient time to consider participating or not. There will be at least 24 hours between provision 
of the information sheet and consent. The Investigator will answer any questions that the 
participant has concerning study participation.  
All participants will have a good command of the English Language and have capacity to 
consent. Any participant who loses capacity after giving consent or withdraws consent will be 
withdrawn from the study. Identifiable data or tissue already collected with consent would be 
retained and used in the study. No further data or tissue would be collected or any other 
research procedures carried out on or in relation to the participant. No prisoners will be 
approached for this study.  
 
Informed consent will be collected from each participant before they undergo any interventions 
(including physical examination and history taking) related to the study. One copy of this will 
be kept by the participant, one will be kept by the Investigator, and a third will be retained in 
the patient’s hospital records. Only two records will be kept for healthy volunteers, one by the 
participant and the other by the investigator as none will be retained in their hospital records.  
Should there be any subsequent amendment to the final protocol, which might affect a 
participant’s participation in the trial, continuing consent will be obtained using an amended 
Consent form which will be signed by the participant. 
 
STUDY REGIMEN 
We will study a cohort of CD patients (n=60) with active disease as defined by a CD activity 
index (CDAI) of 220-450, faecal calprotectin of >250µg/g and one of the following: 
ileocolonoscopy, CT or MR enterography showing active inflammatory uncomplicated 
disease of the ileum (B1L1 or B1L3 phenotype)14. This information will be obtained from 
patient’s hospital notes and online medical records. Due to the exploratory nature of the 
studies, number of recruits is based on previous literature 8, 15, 16 by our group. Stable doses 
of immunosuppressive agents (12 weeks), or anti-TNF agents (16 weeks) will be permitted. 
A similar subset of age, weight and sex-matched healthy volunteers will be recruited. A 
hospital anxiety and depression scale questionnaire and a health questionnaire will be 
completed by each study participant.  
 
Patient demographics: Data on disease phenotype14, age, gender, weight, body mass 
index, pharmacological, surgical and smoking history will be collected.   
 
1. 
Eating behaviour constructs: Eating behaviour traits will be measured through 
self-reported measures: Three Factor Eating Questionnaire (TFEQ) Restraint, Disinhibition 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
and Hunger subscales17; the Binge Eating Scale18; the Power of Food Scale19, the Dutch 
eating behaviour questionnaire20. Additionally, the Control of Eating Questionnaire will be 
used to assess perceptions of food cravings and control over meal intake during the 
previous 7-days21. These questionnaires will be filled in by the participants at home.  
2. 
Dietary intake: Routine energy intake will be measured using three telephone-
administered 24-h dietary recalls (Automated Multi-Pass Method)22.  
 
Compliance 
There will be no compliance issues with this study. If we have an incomplete participant data 
set it will be removed from the study, but we have the right (as indicated on the consent form) 
to use the data we have. 
 
Criteria for terminating the study 
The participant’s involvement in the study will only be terminated if a) in the case of all study 
participants, the participant wishes to do so or in b) CD participants, if the patient or caring 
clinician feels that the patients is too unwell to carry on with the study. 
 
 
ANALYSES 
 
Methods  
Data will be analysed by Dr Richard Wardle under the supervision of Dr Gordon Moran (CI for 
this study) in collaboration with Dr Graham Finlayson (University of Leeds). Differences in food 
intake (measured as mean total 24 hr kcal intake) and eating behaviour traits and states 
between the three groups (active CD, inactive CD and HV) will be carried out with an analysis 
of variance with a post-hoc Bonferroni correction. To identify potential mechanistic links 
between mean food intake and eating behaviour, these data will be correlated to measures of 
disease activity (CRP and faecal calprotectin). Data will be presented as mean. P<0.05 will be 
considered as significant. Spearman or Pearson test will be used. )  
 
Sample size and justification 
Due to the exploratory nature of this study and lack of previous data, we feel the sample size 
suggested is achievable and will be sufficient to provide robust statistics and 95% confidence 
intervals. This work will provide pilot data to further power downstream work.  
Assessment of efficacy 
The primary and secondary endpoints for this study were listed earlier in the study design 
section. For the appropriate statistical analysis please consult the METHODS section of 
ANALYSES.  
 
Procedures for missing, unused and spurious data 
Participants with missing data will be excluded from the final analysis. 
 
 
 
Definition of populations analysed 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Primary and secondary outcomes will be assessed on both the full analysis set and the per 
protocol set.   
 
The Chief Investigator will assess and classify violations of eligibility criteria and other 
deviations from protocol. Major protocol deviations (violations) from protocol will lead to 
exclusion of a participant from the per protocol set. 
 
 
ADVERSE EVENTS 
 
The occurrence of an adverse event as a result of participation within this study is not expected 
and no adverse event data will be collected.  
 
ETHICAL AND REGULATORY ASPECTS 
 
ETHICS COMMITTEE AND REGULATORY APPROVALS 
The trial will not be initiated before the protocol, informed consent forms and participant and 
GP information sheets have received approval / favourable opinion from the Research Ethics 
Committee (REC), and the respective National Health Service (NHS) Research & 
Development (R&D) department. Should a protocol amendment be made that requires REC 
approval, the changes in the protocol will not be instituted until the amendment and revised 
informed consent forms and participant information sheets (if appropriate) have been reviewed 
and received approval / favourable opinion from the REC and R&D departments. A protocol 
amendment intended to eliminate an apparent immediate hazard to participants may be 
implemented immediately providing that the REC are notified as soon as possible and an 
approval is requested. Minor protocol amendments only for logistical or administrative changes 
may be implemented immediately; and the REC will be informed. 
 
The trial will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, 1996; the principles of Good Clinical Practice, and the Department of 
Health Research Governance Framework for Health and Social care, 2005. 
 
INFORMED CONSENT AND PARTICIPANT INFORMATION 
The process for obtaining participant informed consent will be in accordance with the REC 
guidance, and Good Clinical Practice (GCP) and any other regulatory requirements that might 
be introduced. The investigator or their nominee and the participant shall both sign and date 
the Informed Consent Form before the person can participate in the study. 
 
The participant will receive a copy of the signed and dated forms and the original will be 
retained in the Trial Master File. A second copy will be filed in the participant’s medical notes 
and a signed and dated note made in the notes that informed consent was obtained for the 
trial.  
The decision regarding participation in the study is entirely voluntary. The investigator or their 
nominee shall emphasize to them that consent regarding study participation may be withdrawn 
at any time without penalty or affecting the quality or quantity of their future medical care, or 
loss of benefits to which the participant is otherwise entitled. No trial-specific interventions will 
be done before informed consent has been obtained. 
The investigator will inform the participant of any relevant information that becomes available 
during the course of the study, and will discuss with them, whether they wish to continue with 
the study. If applicable they will be asked to sign revised consent forms. 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
If the Informed Consent Form is amended during the study, the investigator shall follow all 
applicable regulatory requirements pertaining to approval of the amended Informed Consent 
Form by the REC and use of the amended form (including for ongoing participants). 
 
 
RECORDS  
Case Report Forms  
Each participant will be assigned a study identity code number, allocated at randomisation, for 
use on CRFs other study documents and the electronic database. The documents and 
database will also use their initials (of first and last names separated by a hyphen or a middle 
name initial when available) and date of birth (dd/mm/yy). 
CRFs will be treated as confidential documents and held securely in accordance with 
regulations. The investigator will make a separate confidential record of the participant’s name, 
date of birth, local hospital number or NHS number, and Participant Study Number (the Study 
Recruitment Log), to permit identification of all participants enrolled in the study, in accordance 
with regulatory requirements and for follow-up as required. 
CRFs shall be restricted to those personnel approved by the Chief or local Principal 
Investigator and recorded on the ‘Study Delegation Log.’ 
All paper forms shall be filled in using black ballpoint pen. Errors shall be lined out but not 
obliterated by using correction fluid and the correction inserted, initialled and dated. 
The Chief or local Principal Investigator shall sign a declaration ensuring accuracy of data 
recorded in the CRF. 
 
Source documents  
Source documents shall be filed at the investigator’s site and may include but are not limited 
to, consent forms, current medical records, laboratory results and records. A CRF may also 
completely serve as its own source data. Only study staff as listed on the Delegation Log shall 
have access to trial documentation other than the regulatory requirements listed below. 
 
Direct access to source data / documents 
The CRF and all source documents, including progress notes and copies of laboratory and 
medical test results shall made be available at all times for review by the Chief Investigator,  
Sponsor’s designee and inspection by relevant regulatory authorities. 
 
DATA PROTECTION  
All study staff and investigators will endeavour to protect the rights of the trial’s participants to 
privacy and informed consent, and will adhere to the Data Protection Act, 1998. The CRF will 
only collect the minimum required information for the purposes of the trial. CRFs will be held 
securely, in a locked room, or locked cupboard or cabinet. Access to the information will be 
limited to the study staff and investigators and relevant regulatory authorities (see above). 
Computer held data including the study database will be held securely and password 
protected. All data will be stored on a secure dedicated web server. Access will be restricted 
by user identifiers and passwords (encrypted using a one way encryption method). 
Information about the study in the participant’s medical records / hospital notes will be treated 
confidentially in the same way as all other confidential medical information. 
Electronic data will be backed up every 24 hours to both local and remote media in encrypted 
format. 
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
 
 
 
QUALITY ASSURANCE & AUDIT  
 
INSURANCE AND INDEMNITY 
Insurance and indemnity for study participants and study staff is covered within the NHS 
Indemnity Arrangements for clinical negligence claims in the NHS, issued under cover of HSG 
(96)48. There are no special compensation arrangements, but study participants may have 
recourse through the NHS complaints procedures. 
The University of Nottingham as research Sponsor indemnifies its staff, research 
participants and research protocols with both public liability insurance and clinical trials 
insurance. These policies include provision for indemnity in the event of a successful litigious 
claim for proven non-negligent harm.  
 
STUDY CONDUCT 
Study conduct may be subject to systems audit of the Study Master File for inclusion of 
essential documents; permissions to conduct the study; Study Delegation Log; CVs of study 
staff and training received; local document control procedures; consent procedures and 
recruitment logs; adherence to procedures defined in the protocol (e.g. inclusion / exclusion 
criteria, correct randomisation, timeliness of visits); adverse event recording and reporting; 
accountability of study materials and equipment calibration logs. 
 
STUDY DATA  
Monitoring of study data shall include confirmation of informed consent; source data 
verification; data storage and data transfer procedures; local quality control checks and 
procedures, back-up and disaster recovery of any local databases and validation of data 
manipulation. The Chief Investigator, or where required, a nominated designee of the Sponsor, 
shall carry out monitoring of study data as an ongoing activity.  
Entries on CRFs will be verified by inspection against the source data. A sample of CRFs (10% 
or as per the study risk assessment) will be checked on a regular basis for verification of all 
entries made. In addition the subsequent capture of the data on the study database will be 
checked. Where corrections are required these will carry a full audit trail and justification. 
Study data and evidence of monitoring and systems audits will be made available for inspection 
by REC as required. 
 
RECORD RETENTION AND ARCHIVING 
In compliance with the ICH/GCP guidelines, regulations and in accordance with the University 
of Nottingham Research Code of Conduct and Research Ethics, the Chief or local Principal 
Investigator will maintain all records and documents regarding the conduct of the study. These 
will be retained for at least 7 years or for longer if required. If the responsible investigator is no 
longer able to maintain the study records, a second person will be nominated to take over this 
responsibility.  
The study Master File and trial documents held by the Chief Investigator on behalf of the 
Sponsor shall be finally archived at secure archive facilities at the University of Nottingham.  
This archive shall include all trial databases and associated meta-data encryption codes. 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
DISCONTINUATION OF THE STUDY BY THE SPONSOR  
The Sponsor reserves the right to discontinue this study at any time for failure to meet expected 
enrolment goals, for safety or any other administrative reasons.  The Sponsor shall take advice 
as appropriate in making this decision. 
 
STATEMENT OF CONFIDENTIALITY  
Individual participant medical information obtained as a result of this study are considered 
confidential and disclosure to third parties is prohibited with the exceptions noted above. 
 
Participant confidentiality will be further ensured by utilising identification code numbers to 
correspond to treatment data in the computer files. 
 
Such medical information may be given to the participant’s medical team and all appropriate 
medical personnel responsible for the participant’s welfare. If information is disclosed during 
the study that could pose a risk of harm to the participant or others, the researcher will discuss 
this with the Chief Investigator and where appropriate report accordingly. 
 
Data generated as a result of this trial will be available for inspection on request by the 
participating physicians, the University of Nottingham representatives, the REC, local R&D 
Departments and the regulatory authorities. 
 
 
PUBLICATION AND DISSEMINATION POLICY 
 
The study results will be presented at national and international conferences when data 
analyses will be finalised (within 12 months of finishing study). Our data will be published in 
international reports and peer reviewed journals within 12-24 months. Data will be anonymised 
and participants will be unidentifiable.  
 
USER AND PUBLIC INVOLVEMENT 
 
We have involved the patients and public at multiple levels.  
1. Design of the Research: 
We have set up an IBD patient panel during the design phase of the study. We have discussed 
with them the importance of the research question put forward and been reassured by a 
positive response from the panel. Separately, we asked a subgroup of the patient advisory 
group to review the patient-related study documentation and we constructively used their 
feedback into our methodology. 
2. Undertaking the research: 
We will try to involve patient relatives, spouses and carers as healthy volunteers. This is part 
of the feedback from our IBD patient panel group. This will be very useful for patient support. 
3. Dissemination of findings: 
We have been invited to disseminate our findings at the Crohn's and Colitis UK 
Nottinghamshire group meetings. 
The NDDBRU is in the process of developing the role of a “Study Mentor”. This role will be 
filled by a participant in previous clinical trials who will be trained to act as an advisor to study 
participants independently of the research team. Their role will be to act as a point of 
information about the clinical trials process, rather than as a source of clinical advice. 
We hope to appoint to this role in 2014. When the post is filled, participants will be made aware 
of this independent source of advice and information. 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
 
 
STUDY FINANCES 
 
Funding source  
 
Funding secured by internal moneys from the PI. 
Participant stipends and payments 
Participants will be donated £15 at the end of their assessment (completing questionnaires 
and complying with the three telephone-administered 24-h dietary recalls). CD participants re-
assessed in remission will be donated this inconvenience allowance again.  
 
 
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
SIGNATURE PAGES 
 
Signatories to Protocol: 
 
Chief Investigator: (name)__________________________________ 
 
 
Signature:__________________________________ 
 
 
Date: ___________ 
 
 
 

 
 
 
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Eating behaviour in Crohn’s disease- Protocol Version 1.0    19 February 2015 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
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transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
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