Assessment of the Impact of a Personalised Nutrition Intervention in Impaired Glucose Regulation
Phase: NA
Conditions: Pre Diabetes
Sponsor: Imperial College London

 
  
 
ASPIRE-DNA 
  
  
Assessment of the Impact of a Personalised Nutrition 
Intervention in Impaired Glucose Regulation  
  
  
  
  
V1.4 16th March 2020 
  
  
   
MAIN SPONSOR: Imperial College London  
FUNDERS: Clinical Trial Agreement between DnaNudge Ltd. and Dept. of Medicine, 
Imperial College London.    
STUDY COORDINATION CENTRE: Centre for Bio-Inspired Technology, Imperial 
College London  
REC reference: 18/NS/0093  
Protocol authorised by:  
  
  
  
  
 
Name & Role  
Date  
Signature  
 
Prof. Nick Oliver   
16th July 2018  
 
(Chief Investigator)  
  
  
  
 
Prof. Christofer Toumazou   
16th July 2018  
 
(Co-Investigator)  
  
  
    
  
 
Dr. Maria Karvela   
16th July 2018  
 
(Co-Investigator)  
  
  
    
  
 
Dr. Caroline Golden   
16th July 2018  
 
(Study Manager)  
  
  
    
  

 
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Summary of Changes: 
 
Version 
Number 
Date 
Summary of Revisions Made: 
V0.19 
27/02/2019 
Section 4.4  
- 
Substantial amendment 
submitted to include three other 
recruitment pathways. 
V1.0 
18/03/2019 
Section 4.4  
- 
Substantial amendment 
submitted to include the addition 
of Patient Identification Centres 
(PICs)  
 
Also, overall formatting was adjusted to 
make the document more readable (no 
information was changed) 
 
V1.1 
28/05/2019 
Section 4.1:  
- 
Addition of measuring the finger 
prick blood sample via a lab 
analyser as a screening method 
for HbA1c 
 
Section 6.1.1: 
- 
HbA1c added to hematology 
procedure 
 
Section 6.2.1 
- 
Addition of measuring the finger 
prick blood sample via a lab 
analyser as a screening method 
for HbA1c 
- 
Time between Screening and 
Baseline Clinical Visit was 2 
weeks, it is now 3 weeks.  
- 
Time between Baseline Clinical 
Visit and Initial Dietary 
Consultation was 2 weeks, it is 
now 3 weeks.  
- 
Visit Windows changed as 
follows:  
o Visits 2, 3: Window 
changed from +/-3 to +- 
10 working days 

 
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o Visits 4 - 11 : Window 
changed from +/-3 to +- 6 
working days 
 
 
Schematic of Study Design changed to 
reflect the change of a 3 week interval 
(old interval: 2 weeks) between 
screening and the baseline clinical visit, 
and a change of a 3 week interval (old 
interval 2 weeks) between the baseline 
clinical visit and the initial dietary 
consultation   
V1.2 
08/08/19 
 
Section 4.4  
- 
Substantial amendment 
submitted to include two other 
recruitment pathways.  
- 
Community centres added to 
recruitment pathway (5) 
 
The addition of section 6.2.5 Participant 
Testimonials.  
V1.3 
13/09/19 
Section 6.2.5 
- 
Added more detail on the 
types of publication that 
participant testimonials can 
be used for and the 
anonymity of testimonials.  
V1.4 
16/03/20 
The section 12. 2 Trial 
Suspension was added.  
  
  
  
  
  
 
 
 
 
 
 

 
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Study Management Group  
 
Chief Investigator:   
Prof. Nicholas Oliver  
  
      Co-investigators:         Prof. Christofer Toumazou  
                                         Dr. Maria Karvela 
 
 
Statistician:     
Dr. Pierre De Beaudrap   
  
Study Management:   Dr. Caroline Golden  
  
Study Coordination Centre  
For general queries, supply of study documentation, and collection of data, 
please contact:  
  
 
Study Coordinator:  
Dr. Caroline Golden  
 
Address:   
  
Centre for Bio-Inspired Technology  
Bessemer Building  
 
Imperial College London  
  
 
SW7 2AZ  
  
 
  
  
  
Registration: TBC  
 
Tel: +44 7568791304   
  
  
  
  
E-mail: cg811@ic.ac.uk  
Web address: http://www.imperial.ac.uk/bio-inspiredtechnology/nudgeomics/aspire-
dna/  
  
Clinical Queries  
Clinical queries should be directed to Prof. Nick Oliver who will direct the 
query to the appropriate person.  
  
Sponsor  
Imperial College London is the main research Sponsor for this study. For 
further information regarding the sponsorship conditions, please contact the 
Head of Regulatory Compliance at:  
  
  
  
Joint Research Compliance Office  
Imperial College London  
Room 221,   
Medical School Building  
St Marys Campus  
Norfolk Place  
London  
W2 1PG  
  
Tel: 0207 594 9459  
  

 
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Funder  
Clinical Trial Agreement between DnaNudge Ltd. and Dept. of Medicine, Imperial 
College London.    
 
This protocol describes the ASPIRE-DNA study and provides information about 
procedures for entering participants.  Every care was taken in its drafting, but 
corrections or amendments may be necessary. These will be circulated to 
investigators in the study.  Problems relating to this study should be referred, in the 
first instance, to the Study Manager.   
  
This study will adhere to the principles outlined in the UK Policy Framework for Health 
and Social Care Research. It will be conducted in compliance with the protocol, the 
Data Protection Act and other regulatory requirements as appropriate.   
  
  
  
 

 
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Table of Contents  
1  
INTRODUCTION 
14 
1.1  
BACKGROUND 
14 
1.2  
RATIONALE 
15 
2  
OBJECTIVES 
17 
2.1  
PRIMARY OBJECTIVE 
17 
2.2  
SECONDARY OBJECTIVES 
17 
2.3  
EXPLORATORY OBJECTIVES 
17 
3  
STUDY DESIGN 
18 
3.1  
TYPE OF STUDY 
18 
3.2  
DURATION 
18 
3.3  
STUDY POPULATION 
18 
3.4  
DESCRIPTION OF STUDY DESIGN 
18 
 3.5  STUDY OUTCOME MEASURES 
19 
4  
PARTICIPANT ENTRY 
21 
4.1  
PRE-REGISTRATION EVALUATIONS 
21 
4.2  
INCLUSION CRITERIA 
21 
4.3  
EXCLUSION CRITERIA 
21 
4.4  
STRATEGIES FOR RECRUITMENT AND RETENTION 
22 
4.5  
WITHDRAWAL CRITERIA 
23 
4.6  
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
23 
5  
STUDY AGENT(S) AND CONTROL DESCRIPTION 
25 
6  
 STUDY PROCEDURES AND SCHEDULE 
27 
6.1  
STUDY PROCEDURES/EVALUATIONS 
27 
6.1.1  
STUDY SPECIFIC PROCEDURES 
27 
6.1.2  
SPECIMEN PREPARATION, HANDLING AND STORAGE 
27 
6.2 STUDY SCHEDULE 
27 
6.2.1 SCREENING 
27 
6.2.2  
FOLLOW-UP 
28 
6.2.3  
FINAL STUDY VISIT 
30 
6.2.4  
EARLY TERMINATION VISIT 
30 
6.2.5 Participant Testimonials 
31 
6.2.6  
SCHEDULE OF EVENTS TABLE 
32 
7  
ADVERSE EVENTS 
33 
7.1  
DEFINITIONS 
33 
7.2  
REPORTING PROCEDURES 
33 
7.2.1  
NON SERIOUS AES 
33 
7.2.2  
SERIOUS AES 
33 
7.3  
EXPECTEDNESS 
34 
8  
ASSESSMENT AND FOLLOW-UP 
35 
9  
STATISTICS AND DATA ANALYSIS 
36 
9.1  
ANALYSIS DATASETS 
36 
9.2  
THE NUMBER OF PARTICIPANTS 
36 
9.3  
POWER CALCULATION 
36 
9.4  
ANALYSIS OF PRIMARY AND SECONDARY OUTCOME MEASURES 
37 
9.5  
EXPLORATORY ANALYSIS 
38 
10 REGULATORY ISSUES 
39 
10.1  
ETHICS APPROVAL 
39 
10.2  
CONSENT 
39 

 
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10.3  
CONFIDENTIALITY 
39 
10.4  
INDEMNITY 
40 
10.5  
SPONSOR 
41 
10.6  
FUNDING 
41 
10.7  
AUDITS 
41 
11 DATA HANDLING AND RECORD KEEPING 
42 
11.1  
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
42 
11.2  
STUDY RECORDS RETENTION 
42 
11.3  
PROTOCOL DEVIATIONS 
43 
12 STUDY MANAGEMENT 
44 
13 PUBLICATION POLICY 
45 
REFERENCES 
46 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 

 
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GLOSSARY OF ABBREVIATIONS  
RCT  
Randomised Control Trial  
OGTT  
Oral Glucose Tolerance Test  
ICMJE  
International Committee of Medical Journal Editors  
FDA  
Federal Drug Administration  
CI  
Chief Investigator  
CRF  
Case Report Form  
EMEA  
European Medicines Agency   
HOMA  
Homeostasis model assessment  
DNA  
Deoxyribonucleic acid   
ICL  
Imperial College London  
JRCO   
Joint Research Compliance Office  
SNP  
Single Nucleotide Polymorphism  
HDL  
High-Density Lipoprotein  
LDL  
Low-Density Lipoprotein  
GCP  
Good Clinical Practice   
IRB  
Investigational Review Board  
OR  
Odds Ratio  
PR   
Public Relations  
POCT   
Point-Of-Care Testing  
IFG  
Impaired Fasting Glucose  
IGT  
Impaired Glucose Tolerance  
FFQ  
Food Frequency Questionnaire  
PIC 
Patient Identification Centre 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
KEYWORDS  
Pre-diabetic, non-diabetic hyperglycemia, genetics, app-based dietary 
intervention.   
  
     
 
 

 
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STUDY SUMMARY  
  
TITLE Assessment of the Impact of a Personalised Nutrition Intervention 
in Impaired Glucose Regulation  
DESIGN Pilot Study;  
Allocation: RCT  
Intervention model: Parallel assignment with an active control   
Masking: None  
Primary purpose: Prevention  
AIMS • To compare the impact of a DNA-based diet on glucose regulation 
in prediabetic individuals with that of standard care.   
OUTCOME MEASURES Primary outcome (measured at 6 weeks):   
• 
Difference in 0 minutes glucose on 75g oral glucose 
tolerance test between the control arm and the 
intervention arm.  
  
Secondary outcomes:   
• 
Cross-arm and within arm differences (compared to 0 
week 
measurements) 
between 
the 
control 
arm, 
intervention arm, and the exploratory arm, in respect of:  
o 120 minutes glucose on 75g oral glucose tolerance 
test  
o 0 minutes glucose on 75g oral glucose tolerance test 
o HbA1c 
o Weight  
o BMI  
o Lean mass  
o Fat mass  
o Waist circumference  
o Total cholesterol  
o Fasting Triglycerides  
o LDL cholesterol  
o HDL cholesterol  
o HOMA 
Insulin 
sensitivity 
and 
secretion 
measurement  
o 120 minute c-peptide following 75g oral glucose 
tolerance test  
o Systolic blood pressure   
o Diastolic blood pressure  
o Food 
frequency 
(by 
food 
frequency 
questionnaire (FFQ) and 24hour recall)  
o Energy intake  
o Carbohydrate intake  

 
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o Fat intake  
o Saturated fat intake  
o Salt intake  
o Vitamin D  
o Vitamin B6  
o Vitamin B12  
  
All of the above secondary outcomes will be measured at 6 and 
12 weeks, and a follow-up at 26 weeks (with the exception of 
HbA1c which will only be measured at 12 and 26 weeks).  
• 
The number of participant withdrawals during the trial.   
  
  
POPULATION Adults with impaired glucose regulation defined by impaired fasting 
glucose (IFG) or impaired glucose tolerance (IGT) in line with 
WHO criteria (N = 180).  
  
ELIGIBILITY Inclusion criteria:  
• 
Adults over 18 years of age  
• 
Impaired glucose regulation including IFG and IGT by 
fasting glucose, OGTT or HbA1c criteria  
• 
Access to smartphone with an operating system of iOS 
8.0 or above, or Android 4.0 or above.   
  
 
Exclusion criteria:  
  
• 
Diabetes  
• 
Pregnant or planning pregnancy  
• 
Breastfeeding  
• 
Enrolled in other clinical trials  
• 
Have active malignancy or under investigation for 
malignancy  
• 
Severe visual impairment  
• 
Reduced manual dexterity  
• 
Use of psychiatric, anti-diabetic, and/or weight loss 
medication, and/or oral steroids  
• 
Bariatric surgery   
• 
History of illnesses that could interfere with the 
interpretation of the study results (e.g. HIV, Cushing 
syndrome, chronic kidney disease, chronic liver disease, 
hyperthyroidism, hereditary fructose intolerance, alcohol 
or substance abuse)  
• 
Unable to participate due to other factors, as assessed by 
the Chief Investigator   
  

 
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STUDY DURATION 1 year 11 months  
  
PARTICIPANT DURATION  6 months   
 
 NUMBER OF SITES 1   
  
  
  
  
 

 
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SCHEMATIC OF STUDY DESIGN  
 
 Figure 1: Study design. The asterisk indicates the start of the intervention period.  
  
  
  
 
 
 
 
Screening
Randomisation
Control Arm
Intervention Arm 
Exploratory Arm 
(Download DnaNudge App)
Baseline glucose regulation, anthropometric measurements & 
saliva sample for DNA-based dietary guidelines
Initial consultation with dietitian
``
Glucose regulation & anthropometric measurements
Follow-up glucose regulation & anthropometric measurements
Download genetic information to the 
DnaNudge App
Follow-up phone-call with dietitian
Follow-up phone-call with dietitian
Glucose regulation & anthropometric measurements
Weeks
0
6*
8
12
14
18
32
3
Follow-up phone-call with dietitian
Follow-up phone-call with dietitian
```````
NudgeBox Experience

 
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1 INTRODUCTION   
 
1.1  
BACKGROUND   
Diabetes is amongst the most common long term conditions, with the number 
of people affected worldwide quadrupling from 108 million in 1980 to 422 
million in 2014 (Mathers & Loncar 2006). Its prevalence in people over 18 
years of age has risen from 4.7% in 1980 to a staggering 8.5% in 2014 
(Mathers & Loncar 2006). In 2012, there were 1.5 million deaths as a direct 
result of diabetes, making it the 8th leading cause of death amongst both 
sexes, and the 5th leading cause of death amongst women. There were a 
further 2.2 million deaths as a result of complications due to higher-than-
optimal glucose levels (WHO 2016). In 2013, 6% of the UK adult population 
(2.7 million people) were diabetic (Gatineau et al. 2014), 90% of whom had 
type 2 diabetes (UK 2014). A further 5 million people were estimated to be at 
high risk of developing type 2 diabetes (NHS n.d.). This has led to a cost of 
£8 billion per year to the NHS, 80% of which is due to diabetes-related 
complications such as cardiovascular disease, amputations, renal failure and 
sight loss (Hex et al. 2012).  
  
The potential for lifestyle interventions to reduce the progression to type 2 
diabetes from high risk states has been demonstrated in a number of 
randomised control trials (RCTs) in different countries, with a meta-analysis 
of RCTs suggesting that lifestyle intervention in high risk subjects can halve 
the incidence of diabetes (Neil Thomas et al. 2010). The lifestyle modification 
RCTs that show reduced progression to diabetes in high risk subjects have 
given impressive results (Diabetes Prevention Program Research Group 
2002; Pan et al. 1997; Kosaka et al. 2005; Tuomilehto et al. 2001; 
Ramachandran et al. 2006). However, they have been expensive and labour 
intensive, with multiple personal contacts (including in some instances home 
visits) for those in the trial who were deemed to be failing to achieve their 
goals (Diabetes Prevention Program Research Group 2002). Such intensive 
input is not practical on a large scale. Alternative methods to induce 
behavioural change, including contact via mobile phones or home computer, 
have been employed with success in other clinical situations (Ramachandran 
et al. 2013) .  
  
Furthermore, the use of dietary interventions to adjust postprandial glucose 
levels have indicated the potential benefits of an individualised approach. 
Traditional approaches of predicting postprandial glucose level such as 
carbohydrate intake or glycemic index (American Diabetes Association 2015; 
Bao et al. 2011),  have shown mixed results. Carbohydrate intake has been 
shown to be a poor predictor of postprandial glucose levels (Conn & 
Newburgh 1936; Zeevi et al. 2015). In fact, individual responses to 
carbohydrate intake were sufficiently disparate to distinguish two groups of 
carbohydrate-sensitive 
and 
carbohydrate-insensitive 
individuals, 
emphasising the need for an individualised intervention (Zeevi et al. 2015). 
Using the glycemic index of food succumbs to the caveats of examining only 
a single macronutrient profile, and neglecting the wide range of food 
combinations at a given meal, and the proximity of the next/previous meal 

 
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and/or physical exercise (Dodd et al. 2011). The importance of an 
individualised approach is most clearly illustrated by the discrepancy in 
postprandial glucose readings between people who consume identical meals 
(Vrolix & Mensink 2010; Vega-López et al. 2007; Zeevi et al. 2015), 
highlighting the need for a personalised treatment plan.   
  
Personalised nutrition enables health interventions by optimising multiple 
dietary components simultaneously and enhancing motivation to adhere to 
dietary advice. An innovative approach to personalised nutrition has emerged 
in the form of DNA-based dietary advice. This intervention provides people 
with dietary advice that has been tailored to information based on their DNA. 
In a study in which a DNA-based diet was used to treat obesity, the DNA-
based diet had a dramatic effect on the fasting blood glucose levels of 
participants (Arkadianos et al. 2007). 57% of the intervention group (n = 30, 
receiving DNA-based recommendations), achieved fasting blood glucose 
values <5.6mmol/L (100mg/dL), compared to 25% of the control group (n = 
16), 90 days following treatment (OR = 1.98). Notably, the DNA-based 
nutritional advice was not tailored to be a weight loss program, or indeed to 
improve prediabetic biomarkers. It was targeted to optimise the nutrient 
profile of a given individual. Another point of interest was the longevity of the 
effect. The greatest difference between the intervention and control group 
was found >300 days post treatment; the control cohort showed a slight 
increase in BMI, compared to the decrease found in the intervention group. 
This may indicate that there is a greater probability of long-term adherence to 
nutritional guidelines when tailored, actionable DNA-based advice is 
provided. A prospective study examined the potential for DNA-based advice 
to enhance adherence to nutrition protocols (Nielsen & El-Sohemy 2012). 
Participants received general dietary advice, versus the same advice 
supplemented with information based on their DNA (n = 149). Those in the 
intervention group reported a greater understanding of the dietary advice 
(93% versus 78%), they were more likely view the advice as useful (88% 
versus 72%), and they were more interested in receiving further 
recommendations (95% versus 76%).  
  
 
1.2  
RATIONALE  
The standard treatment protocol for pre-diabetic individuals in the UK is a brief 
consultation with their clinician highlighting the dangers of an increased risk 
of diabetes, and some general information regarding healthy eating and the 
benefits of regular physical activity. The individual will subsequently be 
contacted every 3 years to assess the state of their glucose regulation (NICE 
2012). Despite the implementation of this system, incidence rates of diabetes 
have continued to rise over the years. From 1994-2011, the number of women 
diagnosed with diabetes has risen from 1.9 – 4.9%, and 2.9 – 7.0% for men 
(England 2016). In response to this, the NHS launched the NHS Diabetes 
Prevention Program (DPP) in 2016. The aforementioned studies and the 
predictions of the DPP are in agreement that an intensive lifestyle intervention 
can radically reduce incidence rates of diabetes. However, these 
interventions are costly, labour-intensive and require the health system to 

 
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pre-identify prediabetic patients. The last point is one of the greatest 
challenges to any diabetes prevention program, as many at-risk individuals 
will not self-assess to pre-empt a glucose regulation test (Christensen et al. 
2004). Our solution aims to assess the improvement in glucose regulation by 
following a DNA-based diet in comparison with the standard protocol. 
Furthermore, our intervention will assess whether a positive change can be 
implemented by using an app to aid in grocery shopping for a DNA-based 
diet. If effective, this solution could provide a costeffective, widely-distributed, 
easily scalable prevention tool for improving glucose regulation in high risk 
individuals. Moreover, the non-invasive nature of the intervention, paired with 
the autonomy that it provides the individual in choosing their food choices, 
enables it to be a lowrisk intervention. Furthermore, as a DNA-based diet is 
relevant for the general public, it has the potential to perform the preventative 
measures on individuals who do not self-identify as pre-diabetic.  
   
In this pilot study, we propose to use genetic data to guide personalised 
nutrition in people with impaired glucose tolerance to demonstrate the impact 
of personalised nutrition on glucose metabolism, anthropometry, non-glucose 
metabolism and quality of life.  
  
 
 

 
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2  
OBJECTIVES  
 
2.1  
PRIMARY OBJECTIVE  
• To compare differences in the impact of a DNA-based diet and standard 
care in improving glucose regulation in pre-diabetic individuals  
  
 
2.2  
SECONDARY OBJECTIVES  
• 
To assess the ability of a DNA-based diet to improve the macro- and 
micro-nutrient profile of pre-diabetic participants.   
• 
To assess the impact of a DNA-based diet on clinical markers including 
cholesterol, body composition and blood pressure, as they relate to 
diabetes risk.   
• 
Where applicable, to assess changes in anthropometric measurements 
as a result of following a DNA-based diet, where they relate to diabetic 
risk reduction.   
  
  
 
2.3  
EXPLORATORY OBJECTIVES  
• 
To assess the impact of providing DNA-based dietary guidelines via the 
DnaNudge App, on improving glucose regulation in pre-diabetic 
individuals  
• 
To assess the impact of providing DNA-based dietary guidelines via the 
DnaNudge App, on the secondary outcomes outlined in section 2.2.   
• 
To explore the utility of an app as a delivery mechanism for DNA-based 
dietary advice.   
• 
To examine the changes in leptin measurements via saliva samples 
during the study.   
  
 
 
 
 

 
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3 STUDY DESIGN  
 
3.1  
TYPE OF STUDY  
Physiological; pilot study; RCT, parallel design with an active control.   
  
 
3.2  
DURATION  
23 months.   
  
 
3.3  
STUDY POPULATION  
Adults with impaired glucose regulation defined by HbA1c, impaired fasting 
glucose (IFG) or impaired glucose tolerance (IGT) in line with WHO criteria 
(N = 180):  
  
HbA1c:  
• 
< 42 mmol/mol (6.0%): Non-diabetic  
• 
42 < 47 mmol/mol (6.0–6.4%): IGT – Pre-diabetic  
• 
³ 48 mmol/mol (6.5%): Type 2 diabetic  
IFG (World Health Organization 2006):  
• 
Fasting plasma glucose:  6.1mmol/L 
(110mg/dL) 
 
 IFG 
 
6.9mmol/L (125mg/dL)  
• 
2 hr plasma glucose:      < 7.8 mmol/L (140mg/dL)  
  
IGT (World Health Organization 2006):     
• 
Fasting plasma glucose:   < 7mmol/L (126mg/dL)  
• 
2 hour plasma glucose:  7.8mmol/L (140mg/dL)   IGT < 11mmol/L 
(200mg/dL)  
  
 
3.4  
DESCRIPTION OF STUDY DESIGN   
Following informed consent, study participants will undergo baseline 
assessment including assessment of anthropometry, glucose tolerance, 
metabolism and diet. A trial commencement questionnaire (see Appendix 2) 
will be completed by each participant upon entry into the trial, and a trial 
completion questionnaire (see Appendix 4) will be given after 12 weeks of the 
intervention 
and 
after 
the 
26-week 
follow-up 
measurement. 
The 
questionnaires will address lifestyle factors that may impact the outcomes of 
the study, and data regarding DnaNudge App utility. DNA will be sampled 
from saliva from all participants. Two saliva samples will be taken at the 
baseline assessment (Visit 3 – see Table 1). One sample will be used to 
create the DNA-based dietary recommendations and the second sample will 
be used to assess the leptin levels of the participants. Leptin will be measured 
from saliva samples taken at the 6-, 12-, and 26-week clinical visits to assess 
the changes in the hunger hormone during the study. Participants will be 

 
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assigned to one of three cohorts using stratified blocked randomisation by 
age and gender (block size = 15):   
  
1. Control arm (n = 60):  
• 
Participants will receive general health guidelines according to 
the NICE guidelines, as per standard care.    
• 
Active control  
  
2. Intervention arm (n = 60):  
• 
Participants will receive DNA-based health guidelines via a 
genetic report (see Appendix 13).   
  
3. Exploratory arm (n = 60):  
• 
Participants will receive DNA-based health guidelines via the 
DnaNudge App.   
  
The DNA for all arms of the study will be analysed for pre-determined single 
nucleotide polymorphisms (SNPs) relevant to metabolism. Participants in the 
intervention arm, will be provided with a hard-copy of a genetic report (for an 
example report see Appendix 13), which will explain how their SNPs influence 
their dietary habits. Participants in the exploratory arm, will be given 
personalised DNA-based dietary advice via the DnaNudge App. Participants 
in the control arm will be provided with a summary of NICE guidance via a 
dietitian, as per standard care.  
  
Participants will then be reviewed after 6 and 12 weeks with repeat baseline 
measures. Participants in the control arm will be offered a personalised 
nutrition plan on completion of the study. Participants will be asked to 
complete a food frequency questionnaire (see Appendix 12) before their initial 
consultation with the dietitian (Visit 4 – see Table 1), and at the 6-, 12- and 
26-week follow up clinical visits. Participants will also be asked to perform a 
24-hour recall at each follow-up phone call with a dietitian (Visits 5, 7, 9 & 11 
– see Table 1). A summary of the activities for each participant is given in 
Table 1. Data from the App will also be used in exploratory analysis to 
examine usage patterns and decision making as a result of the DNA-based 
dietary recommendations.   
  
See Figure 1 for a diagram of the study design and estimated timeframe.   
  
 
3.5  
STUDY OUTCOME MEASURES  
  
 
Primary outcome:   
  
Difference in 0 minutes glucose on 75g oral glucose tolerance 
test between the control arm and intervention arm at 6 weeks  

 
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Secondary outcomes:   
120 minutes glucose on 75g oral glucose tolerance test  
0 minutes glucose on 75g oral glucose tolerance test  
HbA1c  
Weight  
BMI  
Lean mass  
Fat mass  
Waist circumference  
Total cholesterol  
Fasting Triglycerides  
LDL cholesterol  
HDL cholesterol  
HOMA Insulin sensitivity and secretion measurement  
120 minute c-peptide following 75g oral glucose tolerance test  
Systolic blood pressure  
  
Diastolic blood pressure  
Food frequency (by food frequency questionnaire and 
interviews) Energy intake  
Carbohydrate intake  
Fat intake  
Saturated fat intake  
Salt intake  
Vitamin D  
Vitamin B6  
Vitamin B12  
  
All secondary outcomes will be measured at 6, 12 and 26 weeks (with the 
exception of HbA1c which will only be measured at 12 and 26 weeks).   
  
 
 
 
 

 
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4 PARTICIPANT ENTRY   
  
 
4.1  
PRE-REGISTRATION EVALUATIONS   
  
Potential participants will undergo a screening process prior to entry into the 
study. Potential participants will be invited to the clinical research facility 
where they will be talked through the consent procedure and allowed to ask 
any questions they may have. Following consent and verification that they are 
eligible via the inclusion and exclusion criteria, they will undergo a glucose 
regulation test via finger prick blood sample that will be analysed either via a 
point of care (POC) HbA1c test, or a lab analyser, to measure HbA1c. The 
lab analyser (TOSOH G8 analyser) will be used to assess HbA1c on a 
capillary sample if the Siemens DCA Vantage Analyser POC device is 
unavailable or returns values that are out of the acceptable range for 
accuracy. Both devices will be used in line with manufacturer instructions. If 
a participant is found to be type 2 diabetic they will be referred to their GP for 
further care.   
The HbA1c test results will be interpreted according to WHO criteria:  
• 
HbA1c below 42 mmol/mol (6.0%): Non-diabetic  
• 
HbA1c between 42 and 47 mmol/mol (6.0–6.4%): IGT – Pre-diabetic  
• 
HbA1c of 48 mmol/mol (6.5%) or over: Type 2 diabetic  
 
4.2  
INCLUSION CRITERIA  
In order to be eligible to participate in this study, an individual must meet all 
of the following criteria:  
• 
Provision of signed and dated informed consent form  
• 
Adults over 18 years of age  
• 
Impaired glucose regulation including IFG and IGT by fasting glucose, 
OGTT or HbA1c criteria  
• 
Access to smartphone with an operating system of iOS 8.0 or above, 
or Android 4.0 or above.   
  
 
4.3  
EXCLUSION CRITERIA  
An individual who meets any of the following criteria will be excluded from 
participation in this study:  
• 
Diabetic  
• 
Pregnant or planning pregnancy  
• 
Breastfeeding  
• 
Enrolled in other clinical trials  
• 
Have active malignancy or under investigation for malignancy  
• 
Severe visual impairment  
• 
Reduced manual dexterity  

 
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• 
Use of psychiatric, anti-diabetic, and/or weight loss medication, and/or 
oral steroids  
• 
Bariatric surgery   
• 
History of illnesses that could interfere with the interpretation of the 
study results (e.g. HIV, Cushing syndrome, chronic kidney disease, 
chronic 
liver 
disease, 
hyperthyroidism, 
hereditary 
fructose 
intolerance, alcohol or substance abuse)  
• 
Unable to participate due to other factors, as assessed by the Chief 
Investigator  
  
 
4.4  
STRATEGIES FOR RECRUITMENT AND RETENTION  
Participants will be recruited through some/all of the following approaches:  
1. Communication with Waitrose customers and their partners through 
Waitrose customer/partner communication platforms  
2. Imperial College Healthcare Trust Diabetes Clinics  
3. Healthy volunteer database in the Imperial Clinical Research Facility   
4. NIHR CRN distribution of text messages to individuals chosen by the 
NIHR CRN based on study inclusion/exclusion criteria in London 
Clinical Commissioning Groups (CCGs). 
5. Flyers for display in hospitals/Imperial Clinical Research Facility 
(ICRF), Imperial College London/Community Centre noticeboards. 
6. Advertisement in local London newspapers with same information as 
flyer. 
7. The use of Patient Identification Centres (PICs) to identify and contact 
potential participants through one of the aforementioned approved 
methods e.g. text messages 
8. Advertisement of the study via Diabetes UK through for example, their 
website, social media.  
9. Opportunistic recruitment via either GP staff, Clinic staff, or Trial Team 
staff providing patients with study information before/during/after their 
consultation.   
  
If identified through method (1), (3), (5) and (6), the initial information that will 
be communicated will direct the potential participants to self-assess if they 
may be pre-diabetic by completing the Leicester Risk Score Assessment 
(Gray 
et 
al. 
2010), 
available 
on 
the 
Diabetes 
UK 
website 
(https://riskscore.diabetes.org.uk/start). Participants will be offered the 
opportunity to contact the clinical trial team if they would like to partake in the 
trial. The clinical trial team will then invite the potential participant to the 
Clinical Research Facility for a screening appointment. If identified through 
method (2), (5), (7) and (9), the participants will be identified from the current 
registry of prediabetic individuals who were identified through standard care. 
They will be provided with contact details for the study should they wish to 
participate. If identified through method (8), participants will be directed to the 
clinical trial website and/or the Trial Team contact email address and phone 
number if they would like to find out more information about the trial. Of note, 
patients can only be approached by members of the Trial Team if they have 

 
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given permission via their direct care team. If the potential participant is 
considered eligible by any of the above methods, they will be contacted via 
email or telephone by the clinical trial team to ask them if they would like to 
undergo a screening test at the clinical research facility to assess their 
suitability for the trial.   
  
Given the high rate of diagnosis of diabetes and pre-diabetic individuals by 
the North-West London GP network in 2016, we anticipate the accrual rate 
for N = 180 pre-diabetic individuals to fulfil our planned recruitment schedule 
of N = 60 participants every 3 months.  
  
 
4.5  
WITHDRAWAL CRITERIA  
Each participant has the right to withdraw from the study at any time. In 
addition, the Investigator may discontinue the participation of a participant 
from the study at any time, if the Investigator considers it necessary for any 
reason including:  
• 
Pregnancy  
• 
Ineligibility   
• 
Significant protocol deviation  
• 
Significant non-compliance with treatment regimen or study 
requirements  
• 
Withdrawal of consent  
• 
Loss to follow-up  
  
Following participant withdrawal, no further clinical tests will be performed, 
and no further information will be obtained from the participant’s DnaNudge 
App for the purposes of the trial. All data recorded prior to withdrawal may be 
analysed in the context of determining reasons for withdrawal. Participants 
will have the option of participating in a follow-up interview to ensure patient 
well-being and to provide reasons for withdrawal if they wish. The reason for 
withdrawal will be recorded in the CRF. Participants will not be required to 
provide reasons for withdrawing from the study. Participant withdrawal will 
result in exclusion from the study if the length of time prior to withdrawal is 
not sufficient to provide useful data for the study.   
  
 
4.6  
PREMATURE TERMINATION OR SUSPENSION OF STUDY  
  
This study may be temporarily suspended or prematurely terminated if there 
is a sufficiently reasonable cause. Written notification, documenting the 
reason for study suspension or termination, will be provided by the 
suspending or terminating party to the principal investigators, the JRCO, ICL 
and DnaNudge Ltd. If the study is prematurely terminated or suspended, the 
Trial Manager will promptly inform the JRCO and will provide reason(s) for 
termination or suspension.   
  
Circumstances that may warrant termination or suspension include, but are 
not limited to:   

 
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• 
Demonstration of efficacy that would warrant stopping   
• 
Insufficient compliance to protocol requirements   
• 
Data that are not sufficiently complete and/or evaluable   
  
The study may resume once concerns about protocol compliance and data 
quality are addressed and satisfy the clinical trial team, and ICL.   
  
 
 

 
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5 STUDY AGENT(S) AND CONTROL DESCRIPTION  
The control arm will receive NICE guidelines for prediabetic individuals via a 
consultation with a dietitian. The will also receive 2 follow up phone calls from 
the dietitian during the intervention period, and 2 further follow up phone calls; 
one to accompany the 12-week clinical measurement, and one to accompany 
the 26-week final follow up clinical measurement. A further description of the 
relevant timings of each of the above is given in section 6.2.  
  
The intervention and exploratory arms will receive DNA-based dietary 
recommendations via consultation with the dietitian. The DNA-based dietary 
recommendations are determined via the integration of DNA information, 
scientific nutrigenomic data, and national dietary guidelines. The intervention 
arm will also have follow-up phone calls with the dietitian as per the control 
arm, however the exploratory will only receive the app, and no follow-up 
phone calls.   
  
The DNA of an individual is assessed to determine their genotype for a pre-
defined set of SNPs that relate to their metabolism. Their genotype for each 
SNP is subsequently mapped to the nutrigenetic dietary recommendations in 
the established database of DnaNudge Ltd., that has intensively reviewed 
scientific literature to determine the nutrigenomic correlates of each SNP. 
Furthermore, many of the nutrigenomic links do not act in isolation. Therefore, 
algorithms have been developed to combine all of the genomic data from the 
pre-defined set of SNPs to give the optimal, personalised dietary guidelines 
to each individual.   
  
The genetic analysis will be performed in both the lab in the Centre for Bio-
Inspired Technology at Imperial College London, and in a lab-on-chip device 
called the NudgeBox. The NudgeBox is technology developed by DnaNudge, 
to miniaturise and improve the speed of genetic analysis techniques such that 
they can be performed in the NudgeBox, in front of the user, in approximately 
15 minutes. It will require the participant to take a buccal cheek swab and 
insert it into the DNA cartridge provided. The cartridge will contain the primers 
necessary to analyse metabolism-based SNPs in the saliva sample. The 
cartridge will then be inserted into the NudgeBox, where the genetic analysis 
will be performed. This technology will be demonstrated to each participant 
during their initial consultation with the dietitian.   
  
The exploratory arm will also receive the DnaNudge App to help them with 
their grocery shopping and food choices. The aforementioned nutrigenetic 
information for each individual will be supplied in an easy to use electronic 
format to provide recommendations on demand e.g. via the DnaNudge App 
or other visual indicator. A summary of the equipment being used is provided 
in Appendix 3. The user will scan the barcode of a product using the App, 
which will provide immediate feedback as to whether the food product is good 
for their health, or is incompatible with one or more of their genetic traits. 
Furthermore, the App will then link this data to an internal database of food 
products and produce recommendations of food products that will be very 

 
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similar to the first product but more amenable to their genetic traits. Moreover, 
the App will contain all of the DNA-based dietary recommendations that will 
have been determined via their DNA in a genetic report. It will also contain 
educational information on action steps that they can take to improve their 
health, and how each of their DNA-based guidelines relate to the national 
dietary guidelines.   
  
  
 
 
 
 

 
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6  STUDY PROCEDURES AND SCHEDULE   
  
 
6.1  
STUDY PROCEDURES/EVALUATIONS  
 
6.1.1  
STUDY SPECIFIC PROCEDURES  
The following list of procedures will be performed on all participants:  
• 
Medical history - Participants will be asked a series of questions by 
the research nurse to ensure that they do not meet any of the 
exclusion criteria of the study.  
• 
Genetic testing – saliva samples will be provided.   
• 
Physical examination – Assessment of weight, height, waist 
circumference, blood pressure, lean mass, fat mass.   
• 
Hematology – blood test to examine total cholesterol, HDL 
cholesterol, LDL cholesterol, fasting triglycerides, HbA1c   
• 
Biological specimen collection – saliva samples will be obtained via 
the collection of 2ml of spit per sample. Another saliva sample will be 
provided by means of a buccal cheek swab, to be used in conjunction 
with the NudgeBox.    
• 
Insulin sensitivity – 0 minutes on 75g glucose OGTT, 120 minutes on 
75g glucose OGTT, 120 minutes c-peptide following 75g glucose 
OGTT, HOMA insulin sensitivity and secretion measurement  
• 
Pregnancy test  
• 
Food frequency questionnaire  
• 
Trial commencement and completion questionnaires   
  
 
6.1.2  
SPECIMEN PREPARATION, HANDLING AND STORAGE  
In line with the Human Tissue Act 2004 and the Imperial College London 
Retention Schedule, the saliva sample will be anonymised, and stored for up 
to 5 years after study completion. After this time the sample will be destroyed 
and the data will be kept for up to 10 years after study completion. Blood 
samples will be stored for 1 year after study completion, upon which time they 
will be destroyed and the data will be stored for 10 years after study 
completion.    
  
6.2 STUDY SCHEDULE  
6.2.1 SCREENING  
Visit 1: Study preparation  
• 
Send participants a Participant Invitation Letter (Appendix 8), and PIS 
(Appendix 6).   
• 
Schedule a screening visit for potential participants.  
  
Visit 2: Screening (Day -42 to -0 +/-10 working days)  
• 
Discuss the consent procedure (Appendix 5) and any questions that 
a potential participant may have regarding the trial.  

 
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• 
If the potential participant would like to participate in the trial, they will 
be provided with an opportunity to sign the consent form and the PIS. 
A copy of the consent form will be provided to the participant and a 
copy will be retained by the clinical trial team.   
• 
Review 
medical 
history 
to 
determine 
eligibility 
based 
on 
inclusion/exclusion criteria.   
• 
Perform medical examinations needed to determine eligibility based 
on inclusion/exclusion criteria. This will include a finger prick blood 
sample that will be analysed either using a point-of-care HbA1c test 
using a Siemens DCA Vantage POCT device, or a lab analyser, to 
measure HbA1c levels.  
• 
Send the GP letter (Appendix 7) to the GP of each confirmed 
participant in the trial who has consented to informing their GP of their 
participation in the trial.  
• 
Provide participants with access to online and/or hard-copy food 
frequency questionnaire that they will need to complete for 1 week of 
food intake prior to their first clinical appointment in the trial (Visit 3).    
  
Following confirmed enrolment in Visit 2, participants will undergo assignment 
to one of the three arms of the study.   
  
Visit 3: Baseline clinical measurements (Day -21 +/- 10 working days)   
• 
Verify inclusion/exclusion criteria and consent.   
• 
Perform clinical assessment of glucose regulation and anthropometric 
measurements.   
• 
Obtain urine pregnancy test (if applicable).  
• 
Collect blood sample (15mL).   
• 
Assess blood pressure, weight, height, waist circumference, lean 
body mass, and fat body mass.    
• 
Perform 0 minutes on 75g glucose OGTT, 120 minutes on 75g 
glucose OGTT, 120 minutes c-peptide following 75g glucose OGTT, 
HOMA insulin sensitivity and secretion measurement.   
• 
Provide two saliva samples (2mL each) via spit.   
• 
Complete trial commencement questionnaire.   
  
  
 
6.2.2  
FOLLOW-UP  
For sample scripts for all interactions with the dietitian for each arm of the 
study, see Appendices 9 (control arm), 10 (intervention arm), and 11 
(exploratory arm).   
  
Visit 4: Initial consultation with a dietitian (Day 0 +/- 6 working days)  
 
• 
Perform 30-60 minute consultation with the dietitian 
• 
Perform 24-hour recall of food intake for each participant.   
• 
Intervention and exploratory arms: Provide NudgeBox experience 
whereby the participant will provide a buccal cheek swab to perform on-
site rapid genotyping. This will provide the participant with a visualisation 
of how some of their genetic information is analysed  

 
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• 
Control arm: Provide NICE guidance by verbal and written 
communication as per standard care.   
• 
Intervention arm: Provide DNA-based dietary information in verbal and 
written form to participants.   
• 
Exploratory arm:  Provide DNA-based dietary information via the 
DnaNudge App.   
  
Visit 5: Follow-up phone-call with the dietitian (Day 14 +/- 6 working days) (Control 
and intervention arms only)  
• 
Contact participants for a brief phone-call with the dietitian to address any 
dietary questions/problems.  
• 
Perform 24-hour recall of food intake for each participant.   
  
Visit 6: Glucose regulation review (Day 42 +/- 6 working days)  
• 
Perform clinical assessment of glucose regulation and anthropometric 
measurements.    
o Obtain urine pregnancy test (if applicable).  
o Collect blood sample (15mL).   
o Assess blood pressure, weight, height, waist circumference, 
lean body mass, and fat body mass.    
o Perform 0 minutes on 75g glucose OGTT, 120 minutes on 75g 
glucose OGTT, 120 minutes c-peptide following 75g glucose 
OGTT, HOMA insulin sensitivity and secretion measurement.   
o Provide saliva sample (2mL) via spit.   
• 
Complete FFQ  
  
Visit 7: Follow-up phone-call with the dietitian (Day 56 +/- 6 working days) (Control 
and intervention arms only)  
• 
Contact participants for a brief phone-call with the dietitian to address any 
dietary questions/problems.  
• 
Perform 24-hour recall of food intake for each participant.   
  
Visit 8: Glucose regulation review (Day 84 +/- 6 working days)  
• 
Perform clinical assessment of glucose regulation and anthropometric 
measurements.     
o Obtain urine pregnancy test (if applicable).  
o Collect blood sample (15mL).   
o Assess blood pressure, weight, height, waist circumference, 
lean body mass, and fat body mass.    
o Perform 0 minutes on 75g glucose OGTT, 120 minutes on 75g 
glucose OGTT, 120 minutes c-peptide following 75g glucose 
OGTT, HOMA insulin sensitivity and secretion measurement.   
o Provide saliva sample (2mL) via spit.   
• 
Complete FFQ.  
• 
Complete trial completion questionnaire.    
  

 
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Visit 9: Follow-up phone-call with the dietitian (Day 84 +/- 6 working days) (Control 
and intervention arms only)  
• 
Contact participants for a brief phone-call with the dietitian to address any 
dietary questions/problems.  
• 
Perform 24-hour recall of food intake for each participant.   
  
  
 
6.2.3  
FINAL STUDY VISIT   
Visit 10: Glucose regulation review (follow-up) (Day 182 +/- 6 working days)   
• 
Perform clinical assessment of glucose regulation and anthropometric 
measurements.     
o Obtain urine pregnancy test (if applicable).  
o Collect blood sample (15mL).   
o Assess blood pressure, weight, height, waist circumference, 
lean body mass, and fat body mass.    
o Complete a food frequency questionnaire.  
o Perform 0 minutes on 75g glucose OGTT, 120 minutes on 75g 
glucose OGTT, 120 minutes c-peptide following 75g glucose 
OGTT, HOMA insulin sensitivity and secretion measurement.   
o Provide saliva sample (2mL) via spit.   
• 
Complete FFQ  
• 
Complete trial completion questionnaire.   
  
Visit 11: Follow-up phone-call with the dietitian (Day 182 +/- 6 working days) 
(Control and intervention arms only)  
• 
Contact participants for a brief phone-call with the dietitian to address any 
dietary questions/problems.   
• 
Perform 24-hour recall of food intake for each participant.   
  
 
6.2.4  
EARLY TERMINATION VISIT  
In the case of early termination, an interview will be conducted with the 
participant to determine reasons for termination if appropriate, and/or to 
determine if the data collected thus far may be useful.   
  
  
 
 
 
 

 
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6.2.5 Participant Testimonials 
Once participants have completed their participation in the trial, they may be 
contacted by the Trial Team to see if they would like to provide a testimonial about 
their experience on the clinical trial. This may cover aspects including their 
experience using DnaNudge technology, aspects that they may have found useful, 
what is their opinion on DNA-based dietary guidelines, amongst others. Participants 
will consent to being contacted to see if they would like to provide a testimonial in 
the Informed Consent Form. Participant testimonials will allow for potential 
publication/media release either following the written consent of the participant. This 
may be in journals, newspapers, radio, interviews, TV, social media, websites, 
newsletters, marketing in print and online. When being asked to provide a 
testimonial, participants will be provided with a list of the above media types so that 
they can provide specific permission for which types of publication can be used. The 
testimonials will be published anonymously or with the participant’s name, provided 
the participant has provided permission to do so.  
 
 
 
 
 

 
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6.2.6 SCHEDULE OF EVENTS TABLE  
  
  
 
Table 1: Schedule of events table for a trial participant.   
  
 
 
 
 
 
Activity 
Trial Visit 
Additional information 
1 2 3 4 5 6 7 8 9 10 11  
Send information 
documents to potential 
participants 
x 
 
 
 
 
 
 
 
 
 
 
All participants 
Consent 
 
x 
 
 
 
 
 
 
 
 
 
Screening visit to assess 
glucose regulation 
 
x 
 
 
 
 
 
 
 
 
 
Randomisation  
 
x 
 
 
 
 
 
 
 
 
 
Fill in food frequency 
questionnaire 
 
x 
 
 
 
x 
 
x 
 
x 
 
Trial commencement 
questionnaire 
 
 
x 
 
 
 
 
 
 
 
 
Perform baseline 
measurements 
 
 
x 
 
 
 
 
 
 
 
 
Take saliva sample for 
genetic testing (PCR)  
 
 
x 
 
 
 
 
 
 
 
 
Initial consultation with 
dietitian 
 
 
 
x 
 
 
 
 
 
 
 
Perform NudgeBox 
genetic test  
 
 
 
x 
 
 
 
 
 
 
 
Provided with the 
DnaNudge App 
 
 
 
x 
 
 
 
 
 
 
 
Exploratory arm only 
Follow-up phone-call 
with dietitian 
 
 
 
 
x 
 
x 
 
x 
 
x 
Control and intervention 
arms 
Perform 24-hour food 
recall 
 
 
 
x x 
 
x 
 
x 
 
x 
Control and intervention 
arms 
6-week glucose regulation 
review 
 
 
 
 
 
x 
 
 
 
 
 
All participants 
Take saliva sample for 
leptin testing 
 
 
x 
 
 
x 
 
x 
 
x 
 
12-week glucose 
regulation review 
 
 
 
 
 
 
 
x 
 
 
 
Trial completion 
questionnaire 
 
 
 
 
 
 
 
x 
 
x 
 
26-week glucose 
regulation review 
 
 
 
 
 
 
 
 
 
x 
 
Weight measurement 
 
 
x 
 
 
x 
 
x 
 
x 
 
Height measurement 
 
 
x 
 
 
x 
 
x 
 
x 
 
Body composition 
 
 
x 
 
 
x 
 
x 
 
x 
 
Waist measurement 
 
 
x 
 
 
x 
 
x 
 
x 
 
Blood pressure 
 
 
x 
 
 
x 
 
x 
 
x 
 
Saliva sample (s) 
 
 
x 
 
 
x 
 
x 
 
x 
 
Venous blood test 
 
 
x 
 
 
x 
 
x 
 
x 
 
OGTT 
 
 
x 
 
 
x 
 
x 
 
x 
 
Pregnancy test (if 
applicable) 
 
 
x 
 
 
x 
 
x 
 
x 
 
Follow-up clinical visits 
 
 
 
 
 
x 
 
x 
 
x 
 
 

 
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7 ADVERSE EVENTS  
  
 
7.1  
DEFINITIONS    
Adverse Event (AE): any untoward medical occurrence in a patient or clinical 
study subject.    
  
Serious Adverse Event (SAE): any untoward and unexpected medical 
occurrence or effect that:  
• 
Results in death  
• 
Is life-threatening – refers to an event in which the subject 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 hospitalisation, or prolongation of existing inpatients’ 
hospitalisation  
• 
Results in persistent or significant disability or incapacity  
• 
Is a congenital anomaly or birth defect  
  
Medical judgement should be exercised in deciding whether an AE is serious.  
Important AEs that are not immediately life-threatening or do not result in 
death or hospitalisation but may jeopardise the subject, or may require 
intervention to prevent one of the other outcomes listed in the definition 
above, should also be considered serious.  
  
 
7.2  
REPORTING PROCEDURES  
All adverse events should be reported. Depending on the nature of the event 
the reporting procedures below should be followed. Any questions concerning 
adverse event reporting should be directed to the Chief Investigator in the first 
instance.    
  
 
7.2.1  
NON SERIOUS AES  
All such events, whether expected or not, should be recorded.    
  
 
7.2.2  
SERIOUS AES  
An SAE form should be completed and sent to the Chief Investigator within 
24 hours.  However, relapse and death, and hospitalisations for elective 
treatment of a pre-existing condition do not need reporting as SAEs.  
  
All SAEs should be reported to the North of Scotland REC 1 where in the 
opinion of the Chief Investigator, the event was:  
• 
‘related’, i.e. resulted from the administration of any of the 
research procedures; and  
• 
‘unexpected’, i.e. an event that is not listed in the protocol as an 
expected occurrence  
  

 
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Reports of related and unexpected SAEs should be submitted within 15 days 
of the Chief Investigator becoming aware of the event, using the NRES SAE 
form for non-IMP studies.  The Chief Investigator must also notify the Sponsor 
of all SAEs.  
  
Local investigators should report any SAEs as required by their Local 
Research Ethics Committee, Sponsor and/or Research & Development 
Office.  
  
Contact details for reporting SAEs  
Please send SAE forms to: Prof. Nick Oliver  
Tel: +44 (0)20 3313 1593  (Mon to Fri 09.00 – 17.00)  
  
 
7.3  
EXPECTEDNESS  
The probability of adverse events is expected to be low given the single-
centre nature of the study with a small cohort. The randomisation and diet 
allocation algorithms have been rigorously tested for misallocation.   
  
 
 
 
 

 
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8 ASSESSMENT AND FOLLOW-UP   
For each participant, follow-up measurements will be taken at 26 weeks. This 
will include all of the secondary outcomes outlined above. Participants will 
then complete a questionnaire (see Appendix 4) at the conclusion of the study 
to collect information regarding their experience of the intervention.   
The study will be complete when the 26 week follow-up measurements are 
taken for the final participant in the trial.   
  
 
 
 
 

 
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9 STATISTICS AND DATA ANALYSIS  
 
9.1  
ANALYSIS DATASETS  
Primary analyses will be conducted following the intention to treat (ITT) 
principle. All participants who are randomised into the study will be included 
in the ITT analysis. Such participants constitute the Full Analysis Set (FAS) 
for this study. In addition, the primary endpoint and the main secondary 
outcomes will also be analysed with the Per Protocol Analysis Set (PPS), 
which will consist of those subjects in the FAS who complete the study with 
no significant deviations from the planned protocol procedures.  
  
 
9.2  
THE NUMBER OF PARTICIPANTS  
The total number of participants recruited into the study will be 180. All arms 
of the trial with have 60 participants each.   
  
Participants will be recruited in cohorts of N = 60. Each member of a given 
cohort will be randomly allocated into one of the three arms of the study, as 
per the blocked randomisation method outlined below. The subdivision of the 
recruitment process into cohorts has been implemented in order to:   
  
1. Allow sufficient time to perform the genetic analysis to prepare the 
DNA-based diet for the participants allocated to the intervention and 
the exploratory arms.  
2. Ensure that the data collected is of sufficient quality. If data in the first 
cohort of 60 participants is not deemed to be of sufficient quality, 
appropriate changes will be made to ensure that useful data is 
obtained from subsequent trial participants.   
3. To prevent delayed commencement of the study due to recruitment 
capacity.   
  
Upon enrolment into the trial, each participant will be assigned to a study arm 
based on stratified, blocked randomisation. A block size of 15 will be 
employed, using the stratifications and allocation size according to age and 
gender shown in Table 2.    
  
  
  
Control arm   
Intervention arm  
Exploratory arm  
Women (age =< 40)  
5  
5  
5  
Women (age > 40)  
5  
5  
5  
Men (age =< 40)  
5  
5  
5  
Men (age > 40)  
5  
5  
5  
Table 2: Allocation categories and size for the stratified blocked randomisation of participants.   
 
9.3  
POWER CALCULATION  
Using baseline from the peer-reviewed study that examined the effect of a 
DNA-based diet on obese individuals (Arkadianos et al. 2007), at 90% power 
with an alpha of 0.05, 50 participants are required in each group to 

 
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demonstrate a between-group difference in effect size of -0.5 mmol/L as the 
primary outcome. This assumes a SD of the baseline to endpoint difference 
of 0.6 mmol/L. The sample size will be increased by 20% to 60 participants 
per arm of the study in order to compensate for participants lost to follow up 
(this includes the 10% risk that a given participant will have of becoming type 
2 diabetic within a 12 month period due to their prediabetic state, and a 
subsequent addition to account for those participants who may be lost to 
follow up for other reasons).   
  
 
9.4  
ANALYSIS OF PRIMARY AND SECONDARY OUTCOME MEASURES  
  
Data will be analysed after all primary and secondary outcomes have been 
recorded for the last participant. The primary analysis will be conducted under 
the ITT principle using modified analysis of covariance (ANCOVA) (Yang & 
Tsiatis 2001). Raw and adjusted mean differences in PFG at week 6 between 
the intervention and control arm will be presented with 95% confidence 
interval (95%CI). The adjusted mean difference will be estimated using a 
linear regression model of week 6 FPG to baseline PFG and treatment arm 
adjusted for age and sex. An interaction of baseline FPG with the indicator 
for treatment arm will be included. PFG will be log transformed and variables 
will be centred.   
  
The primary null hypothesis is no difference in W6 FPG between the 
intervention and the control arm. It will be rejected if the adjusted 95%CI of 
the mean difference does not include 0. The robustness of the results will be 
tested using PP analysis and two alternative models (repeated measure 
mixed model and non parametric model). Missing data will be imputed using 
the multiple imputation with chain equation (MICE) method if there is no 
evidence against the assumption of data missing at random.   
  
The secondary analysis will be conducted under the ITT principle. The 
ANCOVA will be used to compare mean difference in FPG, weight, BMI, 
mass, waist, fasting lipids and blood pressure at the different time points (W6, 
W12 and W26). In addition, mixed models will be used to compare the overall 
changes in these outcomes over the all follow up period. Adequacy of the 
models will be assessed through residual plots and Shapiro-Wilk tests for 
normality. Non-parametric methods may be used in case of severe departure 
from normality. In the addition, logistic regression model will be used to 
compare the proportion of participants with IGR between the two arms. 
Change in dietary habits will be analysed using polytomous regression.   
  
For each of the primary and secondary outcomes, formal statistical analysis 
will be based on appropriate linear models. From each linear model, an 
estimate of the magnitude of the treatment effect i.e. the difference in mean 
outcomes between the control arm and intervention arm, will be derived, 
together with adjusted (least squares) means, 95% confidence intervals, and 
associated p-values. Initial exploratory analyses of these models will include 
relevant baseline covariates, including baseline values of the endpoint, and 

 
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all covariates that are statistically significant will be retained in the model for 
the purposes of deriving the final treatment effect outcomes. Baseline values 
of the endpoint will be retained in each model regardless of statistical 
significance.  
  
All analyses will be conducted using two-sided tests and at a significance level 
of 5%.   
  
  
 
9.5  
EXPLORATORY ANALYSIS  
Data collected from the exploratory arm will be used to examine exploratory 
hypotheses. In addition to the data collected from clinical measurements and 
questionnaires, this arm will also provide data via the App. The App will collect 
information regarding usage of features, food choice on the App, amongst 
other App utilisation parameters. This data will be used to explore:  
• 
the efficacy of implementing a DNA-based diet using an App to 
improve glucose regulation in pre-diabetic patients  
• 
the utility of the App to participants in both practical terms (e.g. saving 
time on food choices), and aspiration terms (encouragement to 
pursue a more healthy lifestyle).   
• 
the aspects of the App that were the most/least effective  
• 
how the App influences adherence levels of participants to a healthier 
lifestyle   
  
Additional exploratory analyses may be performed using this arm, if the data 
suggest other effects of interest.  
  
 
 

 
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10 REGULATORY ISSUES  
  
 
10.1  
ETHICS APPROVAL  
The Chief Investigator has obtained approval from the North of Scotland REC 
1. The study must be submitted for HRA and CCC approval at each 
participating NHS Trust.  The Chief Investigator will require a copy of the Trust 
R&D approval letter before accepting participants into the study. The study 
will be conducted in accordance with the recommendations for physicians 
involved in research on human subjects adopted by the 18th World Medical 
Assembly, Helsinki 1964 and later revisions.  
  
 
10.2  
CONSENT   
Consent to enter the study must be sought from each participant only after a 
full explanation has been given, an information leaflet offered and time 
allowed for consideration. Signed participant consent should be obtained. 
The right of the participant to refuse to participate without giving reasons must 
be respected. After the participant has entered the study the clinician remains 
free to give alternative treatment to that specified in the protocol at any stage 
if he/she feels it is in the participant’s best interest, but the reasons for doing 
so should be recorded. In these cases the participants remain within the study 
for the purposes of follow-up and data analysis. All participants are free to 
withdraw at any time from the protocol treatment without giving reasons and 
without prejudicing further treatment.   
  
Please see Appendix 5 for an example consent form.   
 
10.3  
CONFIDENTIALITY  
The Chief Investigator will preserve the confidentiality of participants taking 
part in the study. Following the consent of participants, a participant’s GP may 
be informed of significant findings from physical examination or laboratory 
tests.   
  
It will be necessary for DnaNudge Ltd to be transferred the following 
anonymised data:   
• 
Genetic results  
• 
Participant ID   
• 
Year of Birth  
• 
Ethnicity   
• 
Sex   
This is necessary in order for the algorithms of DnaNudge Ltd to compute the 
DNA-based dietary guidelines that will be provided to participants in the 
intervention and exploratory arms. For participants in the exploratory arm, it 
will also be required to provide participants with an App to provide the DNA-
based dietary guidelines and to guide their grocery shopping choices. Of note, 
DnaNudge Ltd will not receive the names of participants, the only data that 
will be transferred will be anonymised.   

 
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The following is a statement from DnaNudge Ltd. regarding the security of the 
data which they will hold for the ASPIRE-DNA trial:   
  
“How personal information is protected? For the data 
governance approval Buccal mucosal cells samples from the inner 
side of the cheek and the oral cavity of the participant will be 
processed in a small genetic testing device (NudgeBox). The end-to-
end processing of the sample includes inserting the swab sample into 
the disposable cartridge, placing the cartridge in the NudgeBox and 
extracting DNA from the swab sample (a process that can be 
controlled by the participant’s mobile device), amplifying DNA, and 
analysing genetic results. The sample-containing cartridge is single 
use only and is disposed upon completion of the test. An additional 
2ml saliva sample of the participant will be anonymised and 
processed with conventional DNA analysis methods (e.g. PCR, and 
RT-PCR analysis) at the Imperial College laboratory facilities. Both 
genetic analyses, carried out either by the NudgeBox or at the 
Imperial College laboratories, will not examine the whole genetic 
sequence of the participant, but will be focuses on isolated partial 
genetic information (i.e. single-nucleotide polymorphism SNPs) that 
will give us an insight in how a participant is metabolises food, how 
different nutrients affect his/her body, and what impact different 
ingredients have on the participant in the long term. To the best of our 
knowledge, the genetic results provided by our test will not be 
informative enough to trace the personal details of an individual; 
furthermore, we will not perform any test to trace personal details. The 
genetic results, which are encrypted and protected by the password 
set by the participant, will be stored in the participant’s mobile device 
App. The genetic results are also anonymised, encrypted, and 
backed-up in a password-protected and secure cloud service (i.e. 
AWS) maintained by DnaNudge when the mobile device is connected 
to the internet. The genetic results are separated from other data in 
cloud storage and are secured by password-protected mechanism in 
which only the user can access his/her own results through the App 
using his/her log-in and participant ID.  
  
Data deletion  
If a participant would like to have all his/her data deleted, his/her 
account will be deleted in the cloud and he/she will not be able to 
access his/her App. All his/her data (such as genetic results and 
shopping records) and the back-up will be deleted in the cloud.”  
  
  
 
10.4  
INDEMNITY  
Imperial College London holds negligent harm and non-negligent harm 
insurance policies which apply to this study. Imperial College Healthcare NHS 

 
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Trust holds standard NHS Hospital Indemnity and insurance cover with NHS 
Litigation Authority for NHS Trusts in England, which apply to this study.   
  
 
10.5  
SPONSOR  
Imperial College London will act as the Sponsor for this study.  Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.    
  
 
10.6  
FUNDING  
This study will be funded via a clinical trial agreement between Imperial 
College London and DnaNudge Ltd. Participants will be reimbursed for any 
travel expenses incurred, or greater than normal grocery expenses during the 
course of the trial.   
  
 
10.7  
AUDITS   
The study may be subject to inspection and audit by Imperial College London 
under their remit as sponsor and other regulatory bodies to ensure adherence 
to GCP and the UK Policy Framework for Health and Social Care Research.  
  
 
 

 
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11 DATA HANDLING AND RECORD KEEPING  
 
11.1  
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
  
Data collection is the responsibility of the clinical trial staff at the site under 
the supervision of the site PI. The Investigator is responsible for ensuring the 
accuracy, completeness, legibility, and timeliness of the data reported.   
 
All source documents should be completed in a neat, legible manner to 
ensure accurate interpretation of data. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change.   
  
Copies of the electronic CRF (eCRF) will be provided for use as source 
documents and maintained for recording data for each participant enrolled in 
the study. Data reported in the eCRF derived from source documents should 
be consistent with the source documents or the discrepancies should be 
explained and captured in a progress note and maintained in the participant’s 
official electronic study record.   
Clinical data (including AEs, concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into password-
protected hard-drives. The data system includes password protection and 
internal quality checks to identify data that appear inconsistent, incomplete, 
or inaccurate. Clinical data will be entered directly from the source 
documents. Data collected in the study will be stored in the Imperial Clinical 
Research Facility for the duration of the trial. A back up of the data will be 
transferred to the Centre for BioInspired Technology at Imperial College 
London on a weekly basis during the trial via a password-protected hard-
drive. The hard-drive will be transported by designated individuals using the 
Imperial Shuttle Bus. After trial completion, the remainder of the data will be 
transferred to the Centre for Bio-Inspired Technology at Imperial College 
London. This includes the Site Files and Participant Notes. Both during and 
after the trial, anonymised genetic information, sex, ethnicity and year of birth 
will be transferred to the DnaNudge cloud to compute the DNA-based dietary 
guidelines.  
Trial data, blood samples and saliva samples may be used in future research 
by research studies in Imperial College London and in other organisations. 
These organisations may be universities, NHS organisations or companies 
involved in health and care research in this country or abroad. The information 
will only be used by organisations and researchers to conduct research in 
accordance with the UK Policy Framework for Health and Social Care 
Research.  
 
11.2  
STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 10 years after the 
completion of the trial. These documents should be retained for a longer 
period, however, if required by local regulations.   
  

 
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11.3  
PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, or 
GCP requirements. The noncompliance may be either on the part of the 
participant, the Investigator, or the study site staff. As a result of deviations, 
corrective actions are to be developed by the site and implemented promptly.   
  
These practices are consistent with ICH E6:   
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3   
• 
5.1 Quality Assurance and Quality Control, section 5.1.1   
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.   
  
It is the responsibility of the site to use continuous vigilance to identify and 
report deviations within 7 working days of identification of the protocol 
deviation, or within 7 working days of the scheduled protocol-required activity. 
All deviations must be addressed in study source documents, reported to the 
Trial Manager and the study Sponsor. Protocol deviations must be sent to the 
local IRB as per their guidelines. The site study staff is responsible for 
knowing and adhering to their IRB requirements.   
  
 
 

 
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12 STUDY MANAGEMENT  
The Steering Committee will govern the conduct of the study. The Steering 
Committee will be composed of the CI Prof. Nick Oliver, Co-Investigators 
Prof. Chris Toumazou and Dr. Maria Karvela, and Trial Manager, Dr. Caroline 
Golden. The Steering Committee will meet in person at least quarterly. The 
day-to-day management of the study will be co-ordinated by Dr. Caroline 
Golden.    
  
 
12.1  
TRIAL MONITORING  
The monitoring plan has been devised and will be approved by the Sponsor 
before the trial begins.  
 
12. 2.       TRIAL Suspension 
In the event of the Imperial College Healthcare NHS Trust issuing a 
suspension of all non-essential clinical research activity, such as during the 
outbreak of COVID-19 in early 2020, all clinical visits to the ICRF will be 
suspended for the duration of the suspension. Phone-call visits will continue 
to be performed, as advised from the ICRF. For any participants for whom 
their clinical visits were to fall within the suspension period, their intervention 
period will be extended by the length of the suspension and their visits will re-
commence once clinical research has resumed. 
 
 

 
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13 PUBLICATION POLICY  
The Investigators will be involved in reviewing drafts of the manuscripts, 
abstracts, press releases and any other publications arising from the study.  
Authors will acknowledge that the study was funded via a clinical trial 
agreement between Imperial College London and DnaNudge Ltd.  Authorship 
will be determined in accordance with the ICMJE guidelines and other 
contributors will be acknowledged.  
  
  
  
  
 
 

 
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American Diabetes Association, 2015. (4) Foundations of care: education, 
nutrition, physical activity, smoking cessation, psychosocial care, and 
immunization. Diabetes care, 38 Suppl(Supplement_1), pp.S20–30.  
Arkadianos, I. et al., 2007. Improved weight management using genetic 
information to personalize a calorie controlled diet. Nutrition Journal, 6(1), 
p.29.  
Bao, J. et al., 2011. Improving the estimation of mealtime insulin dose in 
adults with type 1 diabetes: the Normal Insulin Demand for Dose 
Adjustment (NIDDA) study. Diabetes care, 34(10), pp.2146–2151.  
Christensen, J.O. et al., 2004. Population-based stepwise screening for 
unrecognised Type 2 diabetes is ineffective in general practice despite 
reliable algorithms. Diabetologia, 47(9), pp.1566–1573.  
Conn, J.W. & Newburgh, L.H., 1936. THE GLYCEMIC RESPONSE TO 
ISOGLUCOGENIC  
QUANTITIES OF PROTEIN AND CARBOHYDRATE. The Journal of 
Clinical Investigation, 15(6), pp.665–671.  
Diabetes Prevention Program Research Group, 2002. Reduction in the 
Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. 
The New England journal of medicine, 346(6), pp.393–403.  
Dodd, H. et al., 2011. Calculating meal glycemic index by using measured 
and published food values compared with directly measured meal 
glycemic index. The American Journal of Clinical Nutrition, 94(4), 
pp.992–996.  
England, N., 2016.  NHS England Impact Analysis of implementing NHS 
Diabetes  
Prevention Programme, 2016 to 2021,  
Gatineau, M. et al., 2014. Adult obesity and type 2 diabetes,  
Gray, L.J. et al., 2010. The Leicester Risk Assessment score for detecting 
undiagnosed Type 2 diabetes and impaired glucose regulation for use 
in a multiethnic UK setting. Diabetic Medicine, 27(8), pp.887–895.  
Hex, N. et al., 2012. Estimating the current and future costs of Type 1 and 
Type 2 diabetes in the UK, including direct health costs and indirect 
societal and productivity costs. Diabetic Medicine, 29(7), pp.855–862.  
Kosaka, K., Noda, M. & Kuzuya, T., 2005. Prevention of type 2 diabetes by 
lifestyle intervention: a Japanese trial in IGT males. Diabetes Research 
and Clinical Practice, 67(2), pp.152–162.  
Mathers, C.D. & Loncar, D., 2006. Projections of global mortality and burden 
of disease from 2002 to 2030. J. Samet, ed. PLoS medicine, 3(11), 
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Neil Thomas, G. et al., 2010. A Systematic Review of Lifestyle Modification 
and Glucose Intolerance in the Prevention of Type 2 Diabetes. Current 
diabetes …, 6(6), pp.378–387.  
NHS, Quality and Outcomes Framework (QOF) for April 2013 - March 2014 
   
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http://content.digital.nhs.uk/catalogue/PUB15751 [Accessed September 
6, 2017].  
NICE, 2012. Type 2 diabetes: prevention in people at high risk,  
Nielsen, D.E. & El-Sohemy, A., 2012. A randomized trial of genetic 
information for personalized nutrition. Genes & nutrition, 7(4), pp.559–
566.  
Pan, X.R. et al., 1997. Effects of diet and exercise in preventing NIDDM in 
people with impaired glucose tolerance. The Da Qing IGT and Diabetes 
Study. Diabetes care, 20(4), pp.537–544.  
Ramachandran, A. et al., 2013. Effectiveness of mobile phone messaging in 
prevention of type 2 diabetes by lifestyle modification in men in India: a 
prospective, parallel-group, randomised controlled trial. The Lancet 
Diabetes & …, 1(3), pp.191–198.  
Ramachandran, A. et al., 2006. The Indian Diabetes Prevention Programme 
shows that lifestyle modification and metformin prevent type 2 diabetes 
in Asian Indian subjects with impaired glucose tolerance (IDPP-1). 
Diabetologia, 49(2), pp.289–297.  
Tuomilehto, J. et al., 2001. Prevention of Type 2 Diabetes Mellitus by 
Changes in Lifestyle among Subjects with Impaired Glucose Tolerance. 
The New England journal of medicine, 344(18), pp.1343–1350.  
UK, D., 2014. Diabetes: Facts and Stats (v3),  
Vega-López, S. et al., 2007. Interindividual variability and intra-individual 
reproducibility of glycemic index values for commercial white bread. 
Diabetes care, 30(6), pp.1412–1417.  
Vrolix, R. & Mensink, R.P., 2010. Variability of the glycemic response to single 
food products in healthy subjects. Contemporary Clinical Trials, 31(1), 
pp.5–11.  
WHO, 2016. Global Report on Diabetes,  
World Health Organization, 2006. Definition and diagnosis of diabetes 
mellitus and intermediate hyperglycemia : report of a WHO/IDF 
consultation. World Hearth Org.  
Yang, L. & Tsiatis, A.A., 2001. Efficiency Study of Estimators for a Treatment 
Effect in a Pretest–Posttest Trial. The American Statistician, 55(4), 
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Zeevi, D. et al., 2015. Personalized Nutrition by Prediction of Glycemic 
Responses. Cell, 163(5), pp.1079–1094.  
  
  
  
  
  
  
  
  
  
  
  
 
 

 
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Appendix 1 
 
ASPIRE-DNA Gantt Chart 
 
 
 

 
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Appendix 2 
 
Commencement questionnaire 
 
 
 

 
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Appendix 3 
 
Summary of equipment 
 
 
 

 
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Appendix 4 
 
Completion questionnaire    
 

 
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Appendix 5 
 
Consent form 
 
 
 

 
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Appendix 6 
 
Participant information sheet 
 
 
 
 

 
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Appendix 7 
 
GP letter 
 
 

 
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Appendix 8 
 
Participant invitation letter 
 
 

 
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Appendix 9 
 
Dietary Intervention Protocol CONTROL Arm  

 
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Appendix 10 
 
Dietary Intervention Protocol INTERVENTION 
Arm  
 

 
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Appendix 11 
 
Dietary Intervention Protocol EXPLORATORY 
Arm 
 
 

 
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Appendix 12 
 
Food Frequency Questionnaire 
 
 

 
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Appendix 13 
 
Sample Genetic Report