Testing the Effectiveness of a Low Carbohydrate Diet With Remote Support for Patients With Type 2 Diabetes in Primary Care, on Weight and Glycaemic Control: a Randomised Controlled Trial
Phase: NA
Conditions: Type 2 Diabetes Mellitus in Obese
Sponsor: University of Oxford

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 1 of 29 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 2 of 29 
Study Title:  Testing the effectiveness of a low carbohydrate diet with remote support for patients with 
type 2 diabetes in primary care, on weight and glycaemic control: a randomised controlled trial  
Internal Reference Number / Short title: REmote SUpport for Low-Carbohydrate Treatment of type 2 
diabetes: the RESULT trial 
Ethics Ref:  21/WM/0101 
IRAS Project ID: 295974 
Date and Version No: V 2.0 16/07/21 
 
Chief Investigator: 
Professor Paul Aveyard 
Nuffield Department of Primary Care Health Sciences, University of 
Oxford; Radcliffe Observatory Quarter, Woodstock Road, Oxford 
 NIHR Oxford Biomedical Research Centre 
 
Paul.aveyard@phc.ox.ac.uk 
Investigators:  
Dr Elizabeth Morris 
Nuffield Department of Primary Care Health Sciences, University of 
Oxford; NIHR Oxford Biomedical Research Centre 
 
Professor Susan Jebb 
Nuffield Department of Primary Care Health Sciences, University of 
Oxford; NIHR Oxford Biomedical Research Centre 
 
 
Sponsor:  
University of Oxford 
Funder: 
This work is supported by the NIHR Biomedical Research Centre, Oxford, 
and the Wellcome Trust Clinical Doctoral Research Fellowship (EM). 
Chief Investigator Signature:  
 
All the investigators declare that they have no potential conflicts of interest. 
 
 
Confidentiality Statement 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 3 of 29 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, HRA, host organisation, and members of the Research Ethics Committee, 
unless authorised to do so. 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 4 of 29 
 
TABLE OF CONTENTS 
 
1. 
KEY CONTACTS .................................................................................................................................. 6 
2. 
LAY SUMMARY .................................................................................................................................. 6 
3. 
SYNOPSIS ........................................................................................................................................... 7 
4. 
ABBREVIATIONS ................................................................................................................................ 9 
5. 
BACKGROUND AND RATIONALE ..................................................................................................... 10 
6. 
OBJECTIVES AND OUTCOME MEASURES ........................................................................................ 11 
7. 
STUDY DESIGN ................................................................................................................................ 13 
8. 
PARTICIPANT IDENTIFICATION ........................................................................................................ 13 
8.1. 
Study Participants ................................................................................................................... 13 
8.2. 
Inclusion Criteria ..................................................................................................................... 13 
8.3. 
Exclusion Criteria .................................................................................................................... 14 
9. 
PROTOCOL PROCEDURES ................................................................................................................ 14 
9.1. 
Recruitment ............................................................................................................................ 14 
9.2. 
Screening and Eligibility Assessment .......................................... Error! Bookmark not defined. 
9.3. 
Informed Consent ................................................................................................................... 15 
9.4. 
Baseline Assessments ............................................................................................................. 15 
9.5. 
Randomisation and blinding ................................................................................................... 16 
9.6. 
Description of study intervention and comparator ................................................................ 16 
9.6.1. 
Intervention group .............................................................................................................. 16 
9.6.2. 
Control group ...................................................................................................................... 17 
9.7. 
Subsequent Visits .................................................................................................................... 17 
9.8. 
Sample Handling ..................................................................................................................... 18 
9.9. 
Early Discontinuation/Withdrawal of Participants ................................................................. 18 
9.10. 
Definition of End of Study ....................................................................................................... 19 
10. 
SAFETY REPORTING ......................................................................................................................... 19 
11. 
STATISTICS AND ANALYSIS .............................................................................................................. 19 
11.1. 
Description of the Statistical Methods .................................................................................... 20 
11.2. 
Sample Size Determination ..................................................................................................... 20 
11.3. 
The Level of Statistical Significance ......................................................................................... 20 
12. 
DATA MANAGEMENT ...................................................................................................................... 20 
12.1. 
Access to Data ......................................................................................................................... 20 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 5 of 29 
12.2. 
Data Recording and Record Keeping ....................................................................................... 20 
13. 
QUALITY ASSURANCE PROCEDURES ............................................................................................... 22 
14. 
PROTOCOL DEVIATIONS .................................................................................................................. 22 
15. 
SERIOUS BREACHES ........................................................................................................................ 22 
16. 
ETHICAL AND REGULATORY CONSIDERATIONS .............................................................................. 23 
16.1. 
Declaration of Helsinki ............................................................................................................ 23 
16.2. 
Guidelines for Good Clinical Practice ...................................................................................... 23 
16.3. 
Approvals ................................................................................................................................ 23 
16.4. 
Reporting ................................................................................................................................ 23 
16.5. 
Transparency in Research ....................................................................................................... 23 
16.6. 
Participant Confidentiality ...................................................................................................... 23 
16.7. 
Expenses and Benefits ............................................................................................................ 24 
17. 
FINANCE AND INSURANCE .............................................................................................................. 24 
17.1. 
Funding ................................................................................................................................... 24 
17.2. 
Insurance ................................................................................................................................. 24 
17.3. 
Contractual arrangements ...................................................................................................... 24 
18. 
PUBLICATION POLICY ...................................................................................................................... 24 
19. DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL PROPERTY 25 
19. 
REFERENCES .................................................................................................................................... 25 
20. 
APPENDIX A:  STUDY FLOW CHART ................................................................................................. 26 
21. 
APPENDIX B:  SCHEDULE OF STUDY PROCEDURES ......................................................................... 27 
22. 
APPENDIX C:  AMENDMENT HISTORY ............................................................................................. 28 
 
 
 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 6 of 29 
1. KEY CONTACTS 
 
Chief Investigator 
Professor Paul Aveyard 
Nuffield Department of Primary Care Health Sciences, University of 
Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford 
NIHR Oxford Biomedical Research Centre 
paul.aveyard@phc.ox.ac.uk 
Sponsor 
University of Oxford   
 
Funder(s) 
This work is supported by the NIHR Biomedical Research Centre, 
Oxford, and the Wellcome Trust Clinical Doctoral Research Fellowship 
(EM). 
Committees 
Trial Management Group: Dr Elizabeth Morris, Professor Paul Aveyard, 
Professor Susan Jebb, Dr Jadine Scragg, Dr Michaela Noreik 
Trial  Steering Committee: Professor Jonathan 
Pinkney, jonathan.pinkney@plymouth.ac.uk (chair of the TSC), Dr 
Bethany Shinkins, B.Shinkins@leeds.ac.uk, Dr Amelia 
Hollywood, A.Hollywood@reading.ac.uk, Mr Derek 
Jerome, dclj2001@yahoo.co.uk 
 
 
2. LAY SUMMARY  
 
The standard for diabetes management is changing.  What was previously thought to be a 
lifelong progressive condition to be managed primarily with increasing doses of 
medications, may instead be put into remission (achieving normal or near-normal blood 
glucose levels without medications) if treated with intensive weight loss support. However, 
the majority of patients with type 2 diabetes still rely on general dietary advice from 
primary care professionals. While there is considerable uncertainty regarding the optimal 
diet composition for people with type 2 diabetes, there is a growing interest from patients, 
practitioners and the general public in using real-food, low carbohydrate diets to achieve 
weight loss, improved glycaemic control and even disease remission.  A recent small-scale 
study demonstrated that it was possible, and effective in the short-term, for practice nurses 
in primary care to support patients with type 2 diabetes to adopt a real-food, low-
carbohydrate weight loss diet.  However the patients and healthcare professionals who 
took part in this study were keen to know whether digital interventions and app-based 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 7 of 29 
support could be an alternative way to achieve the same results, with the potential for more 
frequent support without increasing the demand on the primary care workforce. This study 
aims to investigate whether an app-based low-carbohydrate intervention with remote behavioural 
support is effective at improving glycaemia, weight, and other markers of cardiometabolic risk, for 
people with type 2 diabetes in primary care. 
 
3. SYNOPSIS 
 
Study Title 
Testing the effectiveness of low carbohydrate diet with remote support for 
patients with type 2 diabetes in primary care, on weight and glycaemic 
control: a randomised controlled trial 
Internal ref. no. / short 
title 
Low Carb App 
Study registration 
Clinicaltrials.gov: NCT04916314 
Sponsor  
University of Oxford  
Funder  
NIHR Oxford Biomedical Research Centre (BRC) 
Wellcome Trust 
Study Design 
Individually randomised controlled trial 
Study Participants 
Adult men and women with type 2 diabetes and BMI ≥27kg/m2 (30 if 
recorded as white ethnicity) 
Sample Size 
100 (50 intervention, 50 control) 
Planned Study Period 
01/08/2021 – 01/10/2023 
Per participant: 12 months   
Planned Recruitment 
period 
01/08/2021-31/12/2021 
 
Objectives 
Outcome Measures 
Timepoint(s) 
Primary 
 
To determine the 
effectiveness of an app-
based programme offering 
support for a low energy, low 
carbohydrate diet on 
glycaemia, compared with 
usual care in people with 
type 2 diabetes 
Change in participants’ 
HbA1c from baseline 
to 
3 
months 
and 
baseline to 1 year (co-
primary outcomes) 
 
Baseline, 3 
months, 1 year 
Secondary 
 
 
• To determine the effect of 
an app-based programme 
offering support for a low 
energy, low carbohydrate 
diet on remission of type 2 
 
Number of 
participants meeting 
consensus definition 
for remission from 
 
1 year 
 
 
 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 8 of 29 
diabetes compared with 
usual care 
 
• To determine the effect 
(Short- and longer-term) of 
an app-based support 
programme for dietary 
change in type 2 diabetes 
on weight, compared with 
usual care 
 
• To determine the effect of 
an app-based programme 
offering support for a low 
energy, low carbohydrate 
diet  on other markers of 
cardiometabolic risk, 
compared to usual care 
 
 
 
 
 
 
 
 
 
• To determine the effect of 
an app-based programme 
offering support for a low 
energy, low carbohydrate 
diet on diabetes related 
distress and quality of life 
 
 
 
 
 
type 2 diabetes at 1 
year 
 
 
Change in 
participants’ weight 
from baseline to 3 
months and baseline 
to 1 year 
 
 
 
Change in 
participants’: 
- Blood pressure 
(systolic and 
diastolic)  
-Lipid profile (total-, 
HDL- and LDL- 
cholesterol, 
triglycerides) 
-Liver function 
(Bilirubin, ALT, ALP, 
Albumin) 
 
Change in 
participants’ PAID 
score and EQ5D 
 
 
Interviews with 
participants 
 
 
 
Baseline, 3 
months, 1 year 
 
 
 
 
 
Baseline, 3 
months, 1 year 
 
 
 
 
 
 
 
 
Baseline, 3 
months, 1 year 
 
 
 
3 months 
Process Measures 
• To examine engagement 
with the programme 
 
 
 
 
 
 
 
 
 
 
• 
Data will be 
collected on 
measures of 
engagement with 
the three main 
components of the 
programme 
(“Learn”, “Track”, 
and “Support”), via 
the app 
programme, and 
change in dietary 
Baseline, 3 
months, 12 
months 
 
 
 
 
 
 
 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 9 of 29 
 
 
 
 
 
• To examine the 
demographic profile of 
participants 
 
• 
To explore participants’ 
experience of using the 
app-based support 
intake patterns 
(via Intake24 24 
hour dietary recall 
questionnaire) 
 
• 
Data (age, gender, 
ethnicity, level of 
education, 
deprivation index, 
dietary 
preference) will be 
collected via 
questionnaire 
• 
Interviews with 
participants 
 
 
 
 
 
 
Baseline 
 
 
3 months 
Intervention(s) 
“SecondNature” App: remote support for a low-carbohydrate dietary 
intervention for weight loss 
Comparator 
Usual care  
 
4. ABBREVIATIONS 
 
CI 
Chief Investigator 
CRF 
Case Report Form 
CTRG 
Clinical Trials & Research Governance, University of Oxford 
FBC 
Full Blood Count 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
HbA1c 
Glycosylated Haemoglobin A1c 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
IG 
Information Governance 
LFTs 
Liver Function Tests (Bilirubin, ALT (Alanine aminotransferase), AST (Aspartarte 
aminotransferase), ALP (Alkaline Phosphatase), Albumin)  
NHS 
National Health Service 
RES 
Research Ethics Service 
OXTREC 
Oxford Tropical Research Ethics Committee 
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&D 
NHS Trust R&D Department 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 10 of 29 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 
T2DM 
Type 2 diabetes mellitus 
 
5. BACKGROUND AND RATIONALE 
There are an estimated 4 million people living with type 2 diabetes (T2D) in the UK, with numbers 
expected to rise to 5 million by 2025  (1). Globally, almost 15% of all deaths are attributable to diabetes 
in the 20-79 years age group, with 47% of those deaths occurring in people under 60 years of age(1). 
Currently, 10% of the NHS annual budget is spent on diabetes (around £10 billion).  
But the paradigm for T2D management is changing.(2)  What was previously thought to be a 
lifelong progressive condition to be managed primarily with escalating doses of 
medications, may instead be put into remission if treated with intensive weight loss 
support(3). However, the majority of patients with type 2 diabetes still rely on general 
dietary advice from primary care professionals. There is considerable uncertainty regarding 
the optimal diet composition for people with T2D, but there is a growing interest from 
patients and practitioners in using real-food, low carbohydrate diets to achieve weight loss, 
improved glycaemic control and even disease remission. 
In our previous DIAMOND study, a randomised controlled feasibility trial (n=33), we demonstrated that it 
was feasible and acceptable for practice nurses to support patients with T2D to adopt a real food, low-
energy, low-carbohydrate weight loss diet in primary care.  On average, participants in the intervention 
group achieved clinically significant improvements in weight and HbA1c in the short-term (12 weeks)(4).  
Recruitment was from April-October 2018; Participant follow up appointments were from August 2018-
February 2019.  Participants received no further formal support or intervention after the 12 week period.   
After study completion, healthcare professionals and participants in qualitative interviews expressed an 
interest in whether the programme could be expanded to include app-based or other remote support.  
Patients were keen to consider increased levels and modes of support, and the potential for a 
synchronous “community” of participants to support each other, while practitioners were concerned 
about adequate workforce capacity and time constraints of delivering increased contacts within primary 
care. 
With increasing interest in remote monitoring and digital support options during the Covid19 pandemic, 
as well as the NHS Long Term Plan’s focus on development and support of digital interventions, this 
question has become increasingly relevant.  Many programmes aiming to support weight loss and 
improvement in control of T2D – or even disease remission – are based on evidence from trials of 
programmes with in-person support.  However, when it comes to wider commissioning or roll-out in 
routine care, such programmes are often expanded to include digital delivery of the interventions (such 
as in the National Diabetes Prevention Programme, and Diabetes Remission Total Diet Replacement 
Pilot), sometimes without clear randomised controlled trial evidence that digital versions of the 
programmes will have similar effectiveness. 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 11 of 29 
There is a growing support from observational evidence to suggest that remote support via a digital 
platform can positively affect the weight and glycaemia of patients with type 2 diabetes who engage 
with these interventions. One such platform offering remote behavioural and dietary support for people 
with type 2 diabetes provides a three-month remote behavioural change programme with mentoring 
from a registered dietitian or nutritionist (health coach), encouraging adoption of a low energy, low-
carbohydrate diet, peer group support, structured education articles and activity tracking technology. 
These elements are accessed via a smartphone or web-based application; each participant additionally 
receives an instructional handbook, and recipe book (+/-wireless weighing and activity tracking 
technology). A service evaluation of 190 participants referred as part of routine care from January to July 
2018 found that 75% of patients (n=144) started the programme, and 65.3% (94) of these submitted 
weight readings after 12 months.  Of these, 60% achieved over 5% total body weight loss, and 28.7% 
achieved over 10% body weight loss; the average total 12 month weight change was -7.8kg (+/- 8.6kg). 
28.5% of participating patients attended for a blood test with their GP after 12 months as part of routine 
care; in those with available HbA1c data, there was a statistically significant change in HbA1c compared 
to baseline (mean -10.4mmol/mol, SD +/- 8.6mmol/mol)(5).  An earlier larger cohort of 896 patients who 
completed a similar programme (3 months of “core” support, plus ongoing access to sustainable advice 
and encouragement of weekly engagement) over a 1 year period, comprising both self-funded clients 
and those referred by their GP free of charge, found a significant change in mean weight of -7.12kg (SD 
6.37kg) at 6 months and -6.14kg (SD 9.97 kg) at 12 months compared to baseline measures(6).  While the 
weight and glycaemic changes reported appear promising, and clinically significant, these observational 
studies have several key limitations (including the generalisability of the patient population (a selected 
group of people with high intrinsic motivation to take part, often in locally limited geographical areas); 
observational design and lack of a control or comparator group; and significant loss to follow up and 
absence of follow up data, without the ability to determine why) that preclude drawing reliable 
conclusions as to the programme’s performance and effectiveness. 
Therefore, the aim of this study is to test in a randomised controlled trial whether a low energy, low 
carbohydrate diet delivered via remote support is effective at improving glycaemia, weight, and other 
markers of cardiometabolic risk, for people with type 2 diabetes in primary care. 
Understanding changes in clinical outcome measures and participant behaviours could inform future 
programmes to support people with type 2 diabetes in primary care. 
6. OBJECTIVES AND OUTCOME MEASURES 
 
Objectives 
Outcome Measures  
Timepoint(s) 
of 
evaluation of this 
outcome measure 
(if applicable) 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 12 of 29 
Primary Objective 
To determine the effectiveness of 
an app-based programme offering 
support for a low energy, low 
carbohydrate diet on glycaemia, 
compared with usual care in people 
with type 2 diabetes 
Change in participants’ HbA1c from 
baseline to 3 months and baseline to 1 
year (co-primary outcomes) 
 
Baseline, 3 months, 
1 year 
Secondary Objectives 
• To determine the effect of an 
app-based programme offering 
support for a low energy, low 
carbohydrate diet on remission 
of type 2 diabetes compared with 
usual care 
 
• To determine the effect (Short- 
and longer-term) of an app-based 
support programme for dietary 
change in type 2 diabetes on 
weight, compared with usual 
care 
 
 
• To determine the effect of an 
app-based programme offering 
support for a low energy, low 
carbohydrate diet on other 
markers of cardiometabolic risk, 
compared to usual care 
 
• To determine the effect on 
diabetes related distress and 
quality of life 
 
Number of participants meeting 
consensus definition for remission from 
type 2 diabetes at 1 year 
 
 
Change in participants’ weight from 
baseline to 3 months and baseline to 1 
year 
 
 
 
 
Change in participants’: 
- Blood pressure (systolic and diastolic) 
-Lipid profile (total-, HDL- and LDL- 
cholesterol, triglycerides) 
-Liver function (Bilirubin, ALT, ALP, 
Albumin) 
 
 
 
Change in participants’ PAID score and 
EQ5D,  
 
  
 
1 year 
 
 
 
Baseline, 3 months, 
1 year 
 
 
 
 
 
Baseline, 3 months, 
1 year 
 
 
 
 
 
 
 
Baseline, 3 months, 
1 year 
 
 
Process Measures 
To examine engagement with the 
programme 
 
 
 
 
Data will be collected on measures of 
engagement with the three main 
components of the programme (“Learn”, 
“Track”, and “Support”), via the app 
programme, and change in dietary intake 
 
Baseline, 3 months, 
12 months 
 
 
 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 13 of 29 
 
To examine the demographic 
profile of participants 
 
To explore participants’ experience 
of using the app-based support 
patterns (via Intake24 24 hour dietary 
recall questionnaire) 
Data (age, gender, ethnicity, level of 
education, deprivation index, dietary 
preference) 
will 
be 
collected 
via 
questionnaire 
 
Interviews with participants 
 
 
Baseline 
 
3 months 
 
 
7. STUDY DESIGN 
This is an individually randomised controlled trial.  Participants, recruited via GP practices, will be 
randomised 1:1 with simple randomisation and no stratification to either the intervention group or 
control (usual care).  They will be enrolled in the study for 1 year, of which the intervention (dietary 
support via the app) will run for 3 months.  Most study procedures will be conducted online or remotely 
(by telephone) including: screening, eligibility assessment, informed consent, randomisation, 
engagement with the app-based intervention.   Participants will be asked to attend 3 face to face 
appointments for the research study at their local GP practice for measurements to be taken (weight, 
blood pressure) and blood tests, at baseline, 3 months and 1 year, and will have 1 additional telephone 
contact with their GP or practice nurse before starting the intervention.  Face to face appointments will 
be incorporated with routine clinical appointments when possible. 
 A flow diagram showing the trial design is given in Appendix A 
 
8. PARTICIPANT IDENTIFICATION 
 
8.1. Study Participants 
One hundred adults with type 2 diabetes and a BMI ≥27kg/m2 (≥30kg/m2 if white ethnicity) will be 
recruited.  
8.2. Inclusion Criteria 
• 
Participant is willing and able to give informed consent for participation in the study. 
• 
Male or Female, aged 40 years or above. 
• 
Diagnosed with current type 2 diabetes (i.e. not in remission) in the last 6 years 
• 
BMI of ≥27kg/m2 (≥30kg/m2 if ethnicity recorded as white) 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 14 of 29 
• 
Has a smartphone or computer with internet access (and the correct operating system 
requirements to use the intervention programme)  
• 
Are able to complete the eligibility and baseline assessments online 
• 
Would like to make changes to their diet or lifestyle to improve their diabetes control, lose weight, 
or improve their general health 
8.3. Exclusion Criteria 
The participant may not enter the study if ANY of the following apply: 
• 
Unable to understand the study materials and interventions 
• 
Currently following a weight loss programme (defined as a structured, prescribed and monitored 
programme and not a self-directed weight loss attempt)  
• 
Pregnant, breastfeeding, or planning to become pregnant during the course of the study 
• 
History of bariatric surgery, including gastric banding 
• 
Currently using insulin therapy 
• 
Proliferative diabetic retinopathy, or maculopathy. 
• 
Recent myocardial infarction or stroke (<3 months) 
• 
Renal failure (chronic kidney disease stage 4 or 5) 
• 
Current active treatment for cancer (other than skin cancer treated with curative intent by local 
treatment only) 
• 
Their doctor does not feel they are appropriate to participate for another reason (e.g. active 
eating disorder diagnosis, significant psychological disturbance)  
 
9. PROTOCOL PROCEDURES  
An overview of study procedures is shown in appendix B. 
9.1. Recruitment 
We aim to recruit 100 participants via their GP practices.  Based on a conservative response rate of 10% 
from similar previous studies, we will approach approximately 1000 eligible individuals from 
approximately 10 GP practices in England(7).  The primary care provider will search their electronic 
registers for eligible individuals and GPs will screen out those to whom it would be inappropriate to send 
a letter. The letter from their GP will invite the patient to consider taking part in the study and the 
patient will be directed to the study website for more information and to access the online Participant 
Information Sheet. Contact details for the research team will be available for them to contact to discuss 
the study in more detail and/or ask any questions.  Participants wishing to be considered for inclusion in 
the trial will be directed to the section of the website to complete the initial eligibility assessment. This 
helps to ensure participants have sufficient IT skills to be able to engage with the intervention. 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 15 of 29 
As part of the initial eligibility assessment participants will be asked to report their height and weight to 
calculate BMI (these numbers will not be recorded, just whether they meet eligibility criteria or not). If 
the participant is ineligible a pop-up will explain that they do not meet the eligibility criteria for this study 
and they will not proceed further and no information will be requested. If they are eligible they will be 
asked to provide their full name and email via an approved secure platform (the SENTRY programming 
system, run by the University of Oxford Nuffield Department of Primary Care Health Sciences Clinical 
Trials Unit, where the information will be stored securely and in compliance with local IG policy) so that 
the research team can contact them. They will also be asked to create a four-digit access code for the 
online consent.  
9.2. Informed Consent 
 
As detailed above (section 9.2) participants will visit a website to read the Participant Information Sheet 
online and able to print out if they wish to. The Participant Information and Informed Consent presented 
to the participants online will detail no less than: the exact nature of the study; what it will involve for 
the participant; the implications and constraints of the protocol; the known side effects and any risks 
involved in taking part. It will be clearly stated that the participant is free to withdraw from the study at 
any time for any reason without prejudice to future care, without affecting their legal rights, and with no 
obligation to give the reason for withdrawal. 
The participant will be allowed as much time as they wish to consider the information and have the 
opportunity to call the research team, their GP or consult other independent parties to ask any questions 
before they decide whether they will participate in the study. Following their initial eligibility assessment 
(section 9.1), eligible participants will be sent an email with a link to the online database where consent 
is taken. They will log in with their full name and access code given previously at the initial eligibility 
assessment (section 9.1). They will then agree to each statement of the consent form and then sign the 
consent form by putting their full name and access code. Once consent has been given, participants will 
click on a link to the electronic data capture system database which will be activated following their 
consent, to complete the baseline assessment. Participants will be able to download a copy of the 
consent form to keep for their records. 
9.3. Baseline Assessments 
All participants will complete a 2 part baseline assessment, firstly online and then at their GP 
practice. 
1. Online:  
Participants will be asked to complete a baseline questionnaire requesting demographic 
information and their current medication, and the standard questionnaires that will be used in 
the study (the Problem Areas in Diabetes (PAID) score, the EQ5D (quality of life assessment), and 
a 24 hour dietary recall questionnaire (“Intake24 dietary assessment tool”, where participants 
are asked to record all food and drink intake in the last 24 hours). This will also further assess 
whether people are sufficiently able to complete online trial procedures, and only those who 
complete the questionnaire will be randomised. Participants will be informed in the Participant 
Information Sheet that they will only be able to enter the study after completing each individual 
questionnaire fully in one attempt as the system will not allow them to go back into each 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 16 of 29 
questionnaire to answer the remaining questions later. Overall there are 3 questionnaires for 
each participant to complete. These should take less than 30 minutes to complete.  Patients will 
be able to fill in the baseline questionnaires and 24 hour dietary recall at any time after 
completion of the online consent form but before the appointment at their GP practice, as long 
as they complete each questionnaire in one attempt.  Should a participant not complete their 
questionnaires, reminder emails will be sent at one and two weeks after they received the initial 
invite to complete the questionnaires.  
 
2. At the GP practice (visit 1) 
Having completed the online assessment, participants will be asked (via message on their screen 
on completing the assessment, and followed up via email) to book the in-person portions of their 
baseline assessment at their GP practice for measures which cannot be conducted online.  At this 
appointment (with a nurse or healthcare assistant), their height, weight and blood pressure will 
be measured and recorded, and a blood sample taken for baseline values (HbA1c, lipid profile, 
liver function tests).  Once their practice confirms they have attended this appointment they will 
be sent a link to the randomisation system. 
9.4. Randomisation and blinding 
All eligible participants will be individually randomised to one of two arms: Intervention (12 week, app-
based dietary support), or control (usual care; no active additional intervention). The randomisation will 
be conducted using the Redcap inbuilt randomisation software. This ensures full allocation concealment 
as information on future allocations is not accessible to the person randomising.  
The participants will be aware that they will be randomised to either an app-based support programme 
or control, therefore no blinding can take place. Due to the nature of the intervention it will not be 
possible to blind members of the study team to participant allocation. A letter will be provided to the 
participant’s GP to inform them of which group the participant has been allocated to. 
9.5. Description of study intervention and comparator 
9.5.1. Intervention group 
Participants randomised to the intervention group will receive an email informing them they have been 
assigned to the intervention group, and that their contact information (name and email) has been 
securely passed to the provider, who will contact them to process the programme onboarding and 
account creation. They will contact the participant with information how to download and access the 
app-based intervention. Thereafter, any identifiable information required by the programme provider 
application will be provided by the participant. The intervention involves diet, activity and behaviour 
change components.  It comprises a three-month remote behavioural change programme with 
mentoring from a registered dietitian or nutritionist (health coach), peer group support, structured 
education articles and activity tracking technology. These elements are accessed via a smartphone or 
web-based application. Each participant will also receive a hard copy of an instructional handbook and a 
recipe book. 
 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 17 of 29 
Participants randomised to the intervention group will also receive 1 additional telephone appointment 
with their GP or practice nurse, towards the start of the 12 week intervention period, to review their 
current medications and assess any changes to their medication regime may be warranted in view of 
their anticipated participation in the programme and planned weight loss. We will provide clinicians with 
current best practice guidelines they may wish to consider but the decisions for individual patients will 
remain with their clinician. 
For participants in the intervention group, data on participant engagement with the app will be received 
from the company under appropriate agreements. These data will include (as examples) measures of 
engagement with the three main components of the programme: Learn, Track, and Support. “Learn” 
interactions are defined as the number of articles read by participants; “Track” interactions are defined 
as the number of times a participant registered or viewed weight readings; “Support” interactions are 
defined as the number of messages sent or read in either the private or group chat channels. 
9.5.2. Control group  
Participants randomised to the control group will receive no additional intervention, and will continue to 
receive their usual NHS diabetes care from their general practice.  
9.6. Subsequent Visits 
All Participants will be followed up after 3 months (visit 2) and at 12 months (visit 3). 
They will be sent a reminder (initially via email or text, followed up by post and/or telephone call if 
required) to inform them to expect contact from their GP practice to book study appointments at both 3 
and 12 months. These appointments are both study research visits.  The appointments will take 
approximately 15 minutes. At this appointment they will have the same procedures as at their baseline 
assessment repeated: their weight and blood pressure will be recorded, and blood tests taken (3 sample 
tubes – for HbA1c, lipid profile and liver function).  These visits will be combined with routine clinical 
care visits where possible. We will explicitly gain consent from participants to be able to extract relevant 
outcome measure data from their medical records during this time period matching that which would 
have been collected at the face-to-face appointments (blood results, weight, blood pressure) (which may 
be used, for example, if a patient is unable to attend their scheduled follow up appointment but has not 
withdrawn from the study and has attended their practice for relevant measurements in the interim). 
They will also be asked to complete the same online questionnaires (PAID score, EQ5D, and 24 hour 
dietary recall) as they completed at baseline, again at 3 and 12 months, with the addition of specific 
questions to proactively ascertain any SAEs which may have occurred (and demographic information will 
not be re-requested as this is not presumed to have changed). 
A purposively sampled proportion of participants from the intervention group (aiming to achieve 
diversity of age, race, and success and engagement with the programme measured by weight/HbA1c 
outcomes and engagement metrics respectively) will be contacted via telephone for a semi-structured 
interview to discuss their experience of the intervention, after they complete the 3 month intervention 
period. Interviews will last approximately 30 minutes. With participants consent this will be audio-
recorded. 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 18 of 29 
After 12 weeks the active intervention period will be complete, but participants will retain access to the 
app interface with stored educational information they have been provided with, and hard copy 
accompanying information, to refer back to if they wish.  
9.7. Sample Handling  
Blood samples for 3 sets of tests (HbA1c, liver function, and lipid profile) will be taken at the 3 specified 
visits, with an approximate maximum total volume of 9ml. All blood samples will be taken, handled, 
analysed and disposed of according to standard NHS procedures and local practice policy.  Blood samples 
will be taken according to the study schedule outlined in appendix B, in order to estimate changes in 
glycaemic control and other biomarkers.  The samples will be sent to NHS laboratories for analysis and 
results reported to the GP following standard procedures.  These data will subsequently be extracted 
from participants’ medical records onto the participant CRF.  
 
9.8. Early Discontinuation/Withdrawal of Participants 
Each participant has the right to withdraw from the trial at any time.   
During the course of the study a participant may choose to withdraw early from the study treatment at 
any time. This may happen for several reasons, including but not limited to: 
• 
The occurrence of what the participant perceives as an intolerable AE.   
• 
Inability to comply with study procedures  
• 
Participant decision  
 
Participants may choose to stop treatment and/or study assessments but may remain on study follow-up.  
Participants may also withdraw their consent, meaning that they wish to withdraw from the study 
completely. If a participant decides to withdraw from treatment, we will seek to retain them in the trial 
for follow-up by explaining the value to the trial of collecting follow up data from all participants by 
speaking with the participants. However, if the participant wishes to withdraw from follow up we will use 
their data up to the point that they withdraw unless they request that we do not do so. The reason for 
withdrawal will be recorded in the electronic case report form (ECRF). Participants that withdraw from 
the trial will not be replaced. Should a participant wish to withdraw, their information that is held with 
the provider, will be retained for 10 years following cease of use. This relates to information provided to 
the intervention provider by the study team and the participant. Cease of use refers to the last login to 
the online programme by the participant. Each participant can request that their personal information 
that is retained by the intervention provider is deleted by contacting either the intervention provider or 
the study team, who will process that request. 
In addition, the Investigator may discontinue a participant from the study treatment at any time if the 
Investigator considers it necessary for any reason including, but not limited to: 
• 
Pregnancy 
• 
Ineligibility (either arising during the study or retrospectively having been overlooked at screening) 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 19 of 29 
• 
Significant protocol deviation 
• 
Clinical decision  
The type of withdrawal and reason for withdrawal will be recorded in the CRF. 
9.9. Definition of End of Study 
The end of study is the point at which the final data is collected -the last 12 month visit of the last 
participant. 
10. SAFETY REPORTING  
10.1. 
 Definition of Serious Adverse Events 
A serious adverse event is any untoward medical occurrence that: 
• 
results in death 
• 
is life-threatening (i.e., an event in which the participant was at risk of death at the time of the 
event; it does not refer to an event which hypothetically might have caused death if it were more 
severe). 
• 
requires inpatient hospitalisation or prolongation of existing hospitalisation 
• 
results in persistent or significant disability/incapacity 
• 
consists of a congenital anomaly or birth defect. 
Other ‘important medical events’ may also be considered serious if they jeopardise the participant or 
require an intervention to prevent one of the above consequences. 
10.2. 
Reporting Procedures for Serious Adverse Events 
The duration of the SAE recording period for each participant lasts from their enrolment on to the study, 
to their completion of the study.  Any serious adverse event (SAE) occurring to a participant will be 
recorded at the time that the research team is made aware of the incident, and reported to the REC that 
gave a favourable opinion of the study where in the opinion of the clinically qualified Chief Investigator 
the event was ‘related’ (resulted from administration of any of the research procedures) and 
‘unexpected’ in relation to those procedures. Reports of related and unexpected SAEs will be submitted 
within 15 working days of the Chief Investigator becoming aware of the event, using the HRA report of 
serious adverse event form, in accordance with HRA process.  We will also proactively ascertain for any 
additional SAEs at the 3 and 12 month outcome data collection timepoints. 
 
11. STATISTICS AND ANALYSIS 
The study results will be reported in accordance with the CONSORT (Consolidated Standards of Reporting 
Trials) 2010 statements (8).  A full analysis plan will be prepared and finalised before any data analysis. 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 20 of 29 
11.1. 
Description of the Statistical Methods  
The primary statistical analysis of efficacy outcomes will be carried out on the basis of intention-to-treat 
(ITT).  This is, after randomisation, participants will be analysed according to their allocated intervention 
group irrespective of what intervention they actually receive.  We will endeavour to obtain full follow-up 
data on every participant to allow full ITT analysis, but we will inevitably experience the problem of 
missing data due to withdrawal, loss to follow up, or non-response to questionnaire items.  
We will analyse the primary continuous outcome with a linear model adjusting for baseline value of the 
relevant variable where relevant. For exploratory analyses, we will use analogous models, but interpret 
the data in an exploratory manner rather than confirmatory. For binary outcomes (e.g. remission), we 
will test for a difference in proportions, e.g. using Fischer’s exact test. 
11.2. 
Sample Size Determination  
Based on previous studies of this intervention(5) and studies in similar populations(3), we estimate an 8-
10mmol/mol change in HbA1c at 12 months in the intervention group in those who engage with the 
programme (SD 8.6mmol/mol), with a 1-2mmol/mol (SD 6mmol/mol) change in the control group.  With 
α and β set at 0.05 this would require approximately 48 participants; however to power for a co-primary 
outcome would require 72 to 88 participants in total (allowing for variability in estimated effect size).  In 
similar trials of behavioural interventions we would expect retention to follow up of >80%; allowing for 
the online nature of this trial, and the retention rates of observational studies of this intervention we will 
aim to recruit 100 participants to allow for cumulative attrition at the intervention sign-up, engagement, 
and follow up stages. 
11.3. 
The Level of Statistical Significance 
The results from the trial will be prepared as comparative summary statistics (difference in proportions 
or means) with 95% confidence intervals.  All the tests will be done at a 5% two-sided significance level.   
12. DATA MANAGEMENT 
The data management aspects of the study are summarised here with details fully described in the Data 
Management Plan.   
12.1. 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor and host institution for 
monitoring and/or audit of the study to ensure compliance with regulations. 
12.2. 
Data Recording and Record Keeping 
The trial is being run with support from the PC-CTU. The data management will be run in accordance 
with the Trials Unit SOPs, which are fully compliant with Good Clinical Practice (GCP). A trial specific Data 
Management Plan (DMP) will be developed for the trial outlining in detail the procedures that will be put 
in place to ensure that high-quality data are produced for statistical analysis.  
A unique trial specific number and/or code in any database will identify the participants.  All data will be 
directly entered online by the participant unless followed- up by the research team, using phone calls, 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 21 of 29 
text messages or email. There will be two databases as all information is collected online and therefore 
identifiable information is also collected. Only the trial team will be able to have access to the databases.   
Trial data will be kept in compliance with the relevant Sponsor’s policy, in particular: the University of 
Oxford: Data Protection Checklist: https://researchsupport.admin.ox.ac.uk/policy/data/checklist and 
Practical: Consideration: https://researchsupport.admin.ox.ac.uk/policy/data/practical 
The data will be stored in Sentry and REDCAP and both are held on University secure servers and the 
University IT team provide security through Firewalls and backups of the systems are taken daily.  
The trial management file and any paper CRFS (if used) will be secured in a locked cabinet in a locked 
room in the Department of Primary Care Health Sciences.   
  
On completion of the trial and data cleaning, the trial documentation will be transferred to a secure, GCP 
compliant archiving facility, where they will be held for five years. Participants’ identifiable information 
will be destroyed at the end of the trial.  Prior to database lock, the Data Manager will undertake a 
dataset review. The anonymised dataset will be stored on a University secure server with access held by 
the Senior Data Manager. Procedures in relation to data transfer are documented within the PC-
CTU_SOP_DM108 and in accordance with the Information Governance Policy.  
 
The audio recordings of telephone interviews will be stored in password protected files, saved under a 
file name of participant ID and no other personally identifiable information, on a secure server. The 
audio recordings will be transcribed by an approved University transcriber with whom appropriate 
information security and confidentiality agreements are in place.  File transfer (of initial audio and then 
transcriptions) will take place using encrypted files and a University IG approved method of data transfer 
(Oxfile), with encryption password sent separately and to a different address.  Transcriptions will be 
pseudonymised as soon as is practical, and original audio recordings deleted as soon as the 
transcriptions have been cross checked and the original audio is no longer required. Pseudonymised 
transcriptions will then be stored in a file on a secure server. 
 
For those who are assigned to the intervention group, participants’ contact information (name and 
email), with consent, will be passed to Second Nature using a secure, encrypted NHS email. All other 
identifiable information, which will be provided by the participant to Second Nature, is governed by their 
privacy policy (available at: secondnature.io/terms). The provider, Second Nature, will retain any 
information held on an individual for up to 10 years after that individual has ceased use of the System. At 
that point, the information will be deleted. As covered in section 5 of the providers’ privacy policy, 
participants may request that personal information is deleted at any time. This referral pathway mirrors 
how this process would work in a real world setting and replicates the current referral pathway to 
Second Nature. Data on participant engagement with the app will be received from the company under 
appropriate agreements. These data will include (as examples) measures of engagement with the three 
main components of the programme: Learn, Track, and Support. “Learn” interactions are defined as the 
number of articles read by participants; “Track” interactions are defined as the number of times a 
participant registered or viewed weight readings; “Support” interactions are defined as the number of 
messages sent or read in either the private or group chat channels. This data will be pseudonymised. 
The participant food diaries will be collected using gold standard dietary analysis programme Intake24, a 
web-based 24 hour dietary recall system.  This system is used for the government-run National Diet and 
Nutrition Survey and is the best available method to collect this data. The Third Party, Intake24, has been 
assessed by the Information Security team at Oxford University, via a Third Party Security Assessment, to 
present a low risk for collection of data of this nature and scale, and is on the IG approved list of third 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 22 of 29 
parties, and all necessary agreements will be in place for use of this third party.  Participants will be sent a 
PID-specific link to complete their dietary recall data; this link will be sent by email by the research team 
(in compliance with all University policies regarding email). Participants will not upload any personal data 
to this platform, it is solely to capture their dietary intake (i.e. what they had to eat and drink in the 
preceding 24 hours). 
 
 
13. QUALITY ASSURANCE PROCEDURES 
The trial will be conducted in accordance with the current approved protocol, GCP, relevant regulations 
and standard operating procedures. 
Regular monitoring will be performed according to GCP. Data will be evaluated for compliance with the 
protocol and accuracy in relation to source documents. Following written standard operating 
procedures, the monitors will verify that the clinical trial is conducted and data are generated, 
documented and reported in compliance with the protocol, GCP and the applicable regulatory 
requirements. 
A Trial Management Group (TMG) will provide oversight of all matters relating to participant safety and 
data quality.  The study is not blinded, carries low risk with no rules for early termination and the trial 
protocol would not be modified based on interim data. Therefore it is felt that it is neither necessary nor 
appropriate to have a specific Data Monitoring and Ethics Committee in addition to the TMG. 
A Trial Steering Committee (TSC) will be formed to provide external oversight of the study and its 
progress. 
14. PROTOCOL DEVIATIONS  
A study related deviation is a departure from the ethically approved study protocol or other study 
document or process (e.g. consent process or administration of study intervention) or from Good Clinical 
Practice (GCP) or any applicable regulatory requirements. Any deviations from the protocol will be 
documented in a protocol deviation form and filed in the study master file. 
15. SERIOUS BREACHES 
A “serious breach” is a breach of the protocol or of the conditions or principles of Good Clinical Practice 
which is likely to affect to a significant degree – 
 (a) the safety or physical or mental integrity of the trial subjects; or 
(b) the scientific value of the research. 
In the event that a serious breach is suspected the Sponsor must be contacted within 1 working day. In 
collaboration with the C.I., the serious breach will be reviewed by the Sponsor and, if appropriate, the 
Sponsor will report it to the approving REC committee and the relevant NHS host organisation within 
seven calendar days.  

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 23 of 29 
16. ETHICAL AND REGULATORY CONSIDERATIONS 
This study involves no identified significant risks to participants. They are primarily consenting to 
engaging with dietary and behavioural advice which is intended to support them to lose weight and 
improve their diabetes control and general health. There are known no significant risks of this advice.  
Venepuncture for blood samples may cause momentary discomfort. Standard NHS operating procedures 
as used in routine clinical care will be used for the collection and processing of samples, and all will be 
carried out by appropriately trained clinicians in the participants’ usual GP practice. 
16.1. 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki.  
16.2. 
Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
16.3. 
Approvals 
Following Sponsor approval the protocol, informed consent form, participant information sheet and any 
additional study documentation will be submitted to an appropriate Research Ethics Committee (REC), 
and HRA (where required) and host institutions for written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
16.4. 
Reporting 
The CI shall submit once a year throughout the study, or on request, an Annual Progress report to the 
REC Committee, HRA (where required) host organisation, Sponsor and funder (where required). In 
addition, an End of Study notification and final report will be submitted to the same parties.  
16.5. 
Transparency in Research  
Prior to the recruitment of the first participant, the trial will have been registered on a publicly accessible 
database.  
Where the trial has been registered on multiple public platforms, the trial information will be kept up to 
date during the trial, and the CI or their delegate will upload results to all those public registries within 
12 months of the end of the trial declaration.  
16.6. 
Participant Confidentiality 
The study will comply with the UK General Data Protection Regulation (GDPR) and Data Protection Act 
2018, which require data to be de-identified as soon as it is practical to do so. The processing of the 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 24 of 29 
personal data of participants will be minimised by making use of a unique participant study number only 
on all study documents and any electronic database(s).  All documents will be stored securely and only 
accessible by study staff and authorised personnel. The study staff will safeguard the privacy of 
participants’ personal data. 
16.7. 
Expenses and Benefits 
Participants will receive a £20 voucher when they provide data at 12 months follow-up.  This is to 
reimburse participants time and encourage retention for the study, and cover any reasonable travel 
expenses to the GP surgery (while not requiring processing of financial data or collation of travel receipts 
on the part of the participants).  Participants may benefit from taking part in this study as they may lose 
weight and some participants will receive free access to a treatment that would usually incur a fee. We 
will share the results of the trial by making them available on our website. 
17. FINANCE AND INSURANCE 
17.1. 
Funding 
The study will be funded by through an NIHR Oxford Biomedical Research Centre (BRC) research grant to 
the Nuffield Department of Primary Care Health Sciences, and the Wellcome Trust Clinical Research 
Fellowship to EM (CI). The research funding will be administered by the University of Oxford. 
17.2. 
Insurance 
The University has a specialist insurance policy in place which would operate in the event of any 
participant suffering harm as a result of their involvement in the research (Newline Underwriting 
Management Ltd, at Lloyd’s of London).  NHS indemnity operates in respect of the clinical treatment that 
is provided. 
 
17.3. 
Contractual arrangements  
Appropriate contractual arrangements will be put in place with all third parties.  
18. PUBLICATION POLICY 
The trial results will be published and all who meet the criteria for authorship will be listed as authors. 
Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be 
acknowledged. The funders will have no role in decisions on publication but authors will acknowledge 
the funding source.  
Other dissemination methods may be used including press releases and social media; the Investigators 
will be involved in reviewing drafts of such items as well as the relevant media teams.  
Participants will be informed of the trial results through an information sheet prepared for a lay audience 
that will be made available on the department website. 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 25 of 29 
19. DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY  
Not applicable 
19. REFERENCES 
 
1. 
DiabetesUK. Facts and Stats. Diabetes UK website, wwwdiabetesorguk. 2015. 
2. 
Morris E, Jebb S, Aveyard P. Type 2 diabetes: treating not managing. The Lancet Diabetes & 
Endocrinology. 
3. 
Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, et al. Primary care-led 
weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. 
The Lancet. 2018;391(10120):541-51. 
4. 
Morris E, Aveyard P, Dyson P, Noreik M, Bailey C, Fox R, et al. A food-based, low-energy, low-
carbohydrate diet for people with type 2 diabetes in primary care: A randomized controlled feasibility 
trial. Diabetes, Obesity and Metabolism. 2019;n/a(n/a). 
5. 
Kar P, Goward C, Whitman M, Davies M, Willner T, Shaw K. Engagement and effectiveness of 
digitally enabled behavioural change support for people living with type 2 diabetes. Practical Diabetes. 
2020;37(5):167-72. 
6. 
Idris I, Hampton J, Moncrieff F, Whitman M. Effectiveness of a Digital Lifestyle Change Program 
in Obese and Type 2 Diabetes Populations: Service Evaluation of Real-World Data. JMIR diabetes. 
2020;5(1):e15189-e. 
7. 
Jolly K, Lewis A, Beach J, Denley J, Adab P, Deeks JJ, et al. Comparison of range of commercial or 
primary care led weight reduction programmes with minimal intervention control for weight loss in 
obesity: Lighten Up randomised controlled trial. 2011;343:d6500. 
8. 
Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: Updated guidelines for reporting 
parallel group randomised trials. J Pharmacol Pharmacother. 2010;1(2):100-7. 
 
 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 26 of 29 
20. APPENDIX A:  STUDY FLOW CHART 
 
Figure 1: CONSORT flow diagram: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessed for eligibility  
Excluded 
• 
Not meeting inclusion criteria 
Randomized 
Consent  
Enrollment 
Completed baseline assessment 
Ineligible as did not complete 
baseline assessments and 
withdrawn 
Allocation 
Allocated to 
intervention group 
(app access) 
Allocated to 
control group 
(usual care)  
Analysis (12 month 
outcomes) 
12 week follow-Up 
12 month follow-Up 
If eligible 
Interim Analysis (3 
month outcomes) 
Optional telephone 
interview 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 27 of 29 
 
21. APPENDIX B:  SCHEDULE OF STUDY PROCEDURES 
 
Activity/Assessment 
Screening  Baseline (Visit 1) 
*INTERVENTION 
Visit 2 
Qualitative 
interview by 
phone* 
Visit 3 
Months 
-1 to 0 
0 
0-3 
3 
3-12 
12 
Length of assessment 
10 mins 
30 mins 
(online) 
15 mins 
(in person) 
3 
months 
30 mins 
30 mins 
15 
mins 
Initial eligibility screening 
X 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
Weight 
 
x 
 
 
X 
 
X 
Height 
 
x 
 
 
X 
 
X 
Blood pressure 
 
x 
 
 
X 
 
X 
Blood test 
 
x 
 
 
X 
 
X 
Randomisation (if eligible) 
 
x 
 
 
 
 
 
Online demographic questionnaire 
 
 
x 
 
 
 
 
Online Questionnaires (PAID, EQ5D, 24 hour 
dietary recall) +/- SAE reporting* 
 
 
x 
 
X 
 
X 
Engagement with app 
 
 
 
*X 
 
 
 
**Telephone medication check 
 
 
 
*X 
 
 
 
**Experience of intervention (qualitative 
interview) by telephone 
 
 
 
 
 
*x 
 
*Can be completed separately to online consent 
**Intervention group only 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 28 of 29 
22. APPENDIX C:  AMENDMENT HISTORY 
 
Amendment 
No. 
Protocol 
Version 
No. 
Date issued Author(s) of changes 
Details of Changes made 
1 
2.0 
01/06/2021 Jadine Scragg 
Section 1 –Typographical 
clarification 
 
Section 3 – Addition of 
study registration detail 
and revised study dates 
 
Section 9.3 – update to 
reflect that the baseline 
questionnaire can be 
completed at any time 
point between 
completion of consent 
and appointment at GP 
practice. 
 
Section 9.5.1 – update to 
reflect the referral 
pathway of patients 
assigned to the 
intervention group to 
the app provider.  
 
Section 9.8- clarification 
of what should happen 
to patient data in the 
event of withdrawal 
 

Date and version No:     V2.0 Date 16/07/21 
 
 
Clinical Research Protocol Template version 15.0  
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Foundation Trust 2019 
 
Page 29 of 29 
Section 12.2 – added 
information to describe 
how participant data will 
be stored, transferred 
and managed