A High-PRotein Mediterranean Diet and Resistance Exercise for Cardiac Rehabilitation: a Pilot Feasibility Study
Phase: NA
Conditions: Cardiovascular Diseases, Sarcopenic Obesity
Sponsor: Liverpool John Moores University

 
 
IRAS ID 256927 
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Research Protocol for IRAS application - LJMU sponsored research 
FULL/LONG TITLE OF THE STUDY: 
A high-PRotein Mediterranean diet and resistance Exercise for cardiac rehabilitation: a pilot randomised 
controlled trial 
 
SHORT STUDY TITLE/ACRONYM 
The PRiME Study  
RESEARCH REFERENCE NUMBERS 
IRAS Number 
256927 
Sponsor reference number 
 
ClinicalTrials.gov number 
 
REC reference number 
 
This protocol has regard for the HRA guidance 
SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that the Chief 
Investigator agrees to adhere to the signed LJMU’s Sponsorship CI declaration. 
 
I agree to ensure that the confidential information contained in this document will not be used for any other 
purpose other than the evaluation or conduct of the investigation without the prior written consent of the 
Sponsor 
 
I also confirm that I will make the findings of the study publically available through publication or other 
dissemination tools without any unnecessary delay and that an honest accurate and transparent account of 
the study will be given; and that any discrepancies from the study as planned in this protocol will be 
explained. 
 
Chief Investigator: 
Signature: 
 
 
 
 
Date: 30/09/2019 
 
Name: (please print): Fatima Perez de Heredia  
 
 
SPONSOR STATEMENT:   
Where LJMU takes on the sponsor role for protocol development oversight, the signing of the IRAS form by 
the sponsor will serve as confirmation of approval of this protocol. 
CONFIDENTIALITY STATEMENT 
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. 
 
 

 
 
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TABLE OF CONTENTS 
 
Full/long title of the study: ................................................................................................................................ 1 
A high-PRotein Mediterranean diet and resistance Exercise for cardiac rehabilitation: a pilot randomised ... 1 
controlled trial ................................................................................................................................................... 1 
Short study title/acronym ................................................................................................................................. 1 
Research reference numbers ............................................................................................................................ 1 
Signature page ................................................................................................................................................... 1 
Sponsor statement: ........................................................................................................................................... 1 
Confidentiality statement .................................................................................................................................. 1 
Table of contents ............................................................................................................................................... 2 
Key study contacts ............................................................................................................................................. 3 
Training / CPD .................................................................................................................................................... 4 
Study summary .................................................................................................................................................. 4 
Funding and support in kind .............................................................................................................................. 5 
Role of study sponsor and funder ..................................................................................................................... 5 
Roles and responsibilities of study management committees/groups and individuals.................................... 6 
Protocol contributors ........................................................................................................................................ 6 
Study flow chart................................................................................................................................................. 7 
Abbreviations..................................................................................................................................................... 8 
1 
Background ................................................................................................................................................ 8 
2 
Rationale .................................................................................................................................................... 8 
3 
Research Question ..................................................................................................................................... 9 
4 
Objectives and outcome measures ........................................................................................................... 9 
5 
Study design and methods of data collection and data analysis............................................................. 10 
5.1 
Randomisation and blinding ........................................................................................................ 10 
5.2 
Baseline assessments .................................................................................................................. 11 
5.3 
Interventions (if applicable)......................................................................................................... 11 
5.4 
Subsequent visits ......................................................................................................................... 12 
5.5 
Study setting ................................................................................................................................ 12 
5.6 
Statistics and analysis .................................................................................................................. 12 
6 
Participant recruitment ........................................................................................................................... 13 
6.1 
Study participants ........................................................................................................................ 13 
6.2 
Inclusion criteria .......................................................................................................................... 13 
6.3 
Exclusion criteria .......................................................................................................................... 13 
6.4 
Recruitment technique ................................................................................................................ 13 
6.5 
Participant identification ............................................................................................................. 14 
6.6 
Screening and eligibility assessment ........................................................................................... 14 
6.7 
Informed consent ........................................................................................................................ 14 
6.8 
Discontinuation/withdrawal of participants from study ............................................................. 14 

 
 
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7 
Data management ................................................................................................................................... 15 
7.1 
Access to data .............................................................................................................................. 15 
7.2 
Data recording and record keeping ............................................................................................. 15 
7.3 
Sample handling .......................................................................................................................... 15 
8 
Safety reporting ....................................................................................................................................... 15 
9 
Quality assurance procedures ................................................................................................................. 15 
10 
Ethical and regulatory considerations ................................................................................................. 15 
10.1 
Declaration of Helsinki ................................................................................................................. 15 
10.2 
Assessment and management of risk .......................................................................................... 16 
10.3 
Participant confidentiality ........................................................................................................... 17 
10.4 
Expenses and benefits ................................................................................................................. 17 
10.5 
Other ethical considerations ....................................................................................................... 17 
10.6 
Research Ethics Committee (REC) and other regulatory review & reports ................................. 17 
11 
Scientific review ................................................................................................................................... 18 
12 
Patient & public involvement .............................................................................................................. 19 
13 
Protocol compliance ............................................................................................................................ 19 
14 
Insurance ............................................................................................................................................. 19 
15 
Contracts and agreements .................................................................................................................. 20 
16 
Definition of end of study .................................................................................................................... 20 
17 
End of study and archiving .................................................................................................................. 20 
18 
Access to the final study dataset ......................................................................................................... 20 
19 
Dissemination policy ............................................................................................................................ 21 
20 
Authorship eligibility guidelines and any intended use of professional writers ................................. 21 
21 
References ........................................................................................................................................... 21 
22 
Appendices .......................................................................................................................................... 23 
22.1 
Appendix 1- required documentation ......................................................................................... 23 
22.2 
Appendix 3 – amendment history ............................................................................................... 23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KEY STUDY CONTACTS 

 
 
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Chief Investigator: 
Dr Fatima Perez de Heredia Benedicte, 01512312003 
F.PerezDeHerediaBenedicte@ljmu.ac.uk 
Investigators:  
Richard Kirwan, 07565427663, r.p.kirwan@2018.ljmu.ac.uk 
Dr Ian Davies, 0151 231 5290, I.G.Davies@ljmu.ac.uk  
Dr Tom Butler, 01244 511660, t.butler@chester.ac.uk (University of 
Chester) 
Prof Gregory Lip, gregory.lip@liverpool.ac.uk (University of Liverpool) 
Prof Dick Thijssen, 0151 904 6246,  D.Thijssen@ljmu.ac.uk (Liverpool 
John Moores University) 
Dr Joseph Mills, 0151 600 1991, joseph.mills@lhch.nhs.uk (Medical 
Director for Advanced Life Support, Liverpool Heart & Chest Hospital NHS 
Trust) 
Sponsor:  
Liverpool John Moores University 
Funder: 
Liverpool Clinical Commissioning Group Research Capability Funding has 
been approved. 
0151 296 7000, enquiries@liverpoolccg.nhs.uk 
Chief Investigator Signature:  
 
 
There are no potential conflicts of interest. 
TRAINING / CPD 
Name 
of 
investigator (add 
new 
row 
if 
required) 
Date 
completed 
LJMU 
REC 
training 
Date completed 
LJMU research 
integrity 
training 
Date completed 
research 
governance 
training 
Date 
completed 
HTA 
training 
(or NA) 
Date 
completed 
other 
training 
(add new 
column if 
required) 
Dr Fatima Perez de 
Heredia 
 
 
 
15/11/2017, 
to 
be 
refreshed 
before starting 
sample 
collection 
 
Dr Ian  Davies 
 
 
 
 
 
Dr Tom Butler 
 
 
 
 
 
Prof Gregory Lip 
 
 
 
 
 
Prof Dick Thijssen 
 
 
 
 
 
Dr Joseph Mills 
 
 
 
 
 
Richard Kirwan 
08/10/2018 
 
 
01/11/2018, 
to 
be 
refreshed 
before starting 
sample 
collection 
 
STUDY SUMMARY 

 
 
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Study Title 
A high-PRotein Mediterranean diet and resistance Exercise for cardiac 
rehabilitation: a pilot randomised controlled trial 
Internal ref. no. / short 
title 
PRiME 
Proposed start date 
January 2020 
Proposed end date 
January 2021 
Countries in which the 
study will take place 
England 
Lead NHS trust & R&D 
contact 
Liverpool Heart & Chest Hospital, Research & Innovation Team (Michael 
Noorzadeh), 01516001158, michael.noorzadeh@lhch.nhs.uk 
Study Design 
2x2 Factorial Randomized Controlled Diet & Exercise Intervention 
Study Participants 
Participants in phase-3 & 4 cardiac rehabilitation 
Planned Sample Size 
Cross-sectional analysis n=240 
Intervention n = 60 (4 groups of 10-15 individuals) 
Planned Study Period 
12 months (3 months for each patient but 7 months allowed for staggered 
recruitment) 
 
 
Objectives 
Outcome Measures 
Primary 
 
Determination of the feasibility of the 
intervention and its applicability in a 
fully powered RCT 
Standard deviation of the key 
secondary 
outcome 
measures, 
willingness of participants to be 
randomised, number of eligible 
participants 
within 
the 
CR 
population, 
follow-up 
rates, 
response rates to questionnaires, 
acceptability of nutritional and 
exercise 
protocols, 
adherence/compliance rates, time 
and finances needed to implement 
the intervention.. 
Secondary 
 
Reduction in the sarcopenic obesity 
index  
Improvement in cardiometabolic risk 
markers 
Body composition measured by 
DXA and anthropometry. 
Changes in cardiometabolic risk 
markers (e.g. lipid profile, fasting 
glucose, HbA1c). 
FUNDING AND SUPPORT IN KIND 
Please provide details of how the study is being funded, both internally and externally.  
FUNDER(S) 
 
FINANCIAL AND NON FINANCIALSUPPORT GIVEN 
LCCG RCF  
£ 27,166 
 
 
ROLE OF STUDY SPONSOR AND FUNDER 

 
 
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The research will be carried out by researchers from LJMU (the study sponsor), in collaboration with Liverpool 
Heart and Chest Hospital (both institutional members of the Liverpool Centre for Cardiovascular Science). 
Funding comes from LJMU and the LCCG RCF. The researchers are not receiving any payments other than 
their usual salaries. 
 
Any support in the form of food products to be used in the intervention will be obtained under the explicit 
agreement that the supplying organization will have absolutely no role in study design, conduct, data analysis 
and interpretation or manuscript writing. The final decision regarding any of these aspects of the study will 
remain with the research team. 
ROLES AND RESPONSIBILITIES OF STUDY MANAGEMENT COMMITTEES/GROUPS AND INDIVIDUALS 
Trial Oversight Committee (TOC): it will consist of the academic investigators, Liverpool Heart and Chest 
clinical leads, and Community centre leads. The TOC will supervise the study in its entirety. 
 
Trial Steering Group (TSG): it will consist of patients engaging with cardiac rehabilitation (CR) (phase 3, patient 
group), the principal investigator, co-investigators, and staff employed on the trial. The TSG will be 
responsible for reviewing the protocol design and ethical considerations, such as participant information, 
and valuable feedback on patient ‘friendliness’ and acceptability will be documented and fed back to the 
TOC. Any changes made will be reported and documented. 
 
Liverpool Heart & Chest Hospital, Service Users Research Endeavour (SURE) group: This is a Patient & Public 
Involvement Group whose membership comprises former or existing patients, carers or members of the 
public.  The SURE group works alongside LHCH Trust’s Research Committee to appraise, monitor and 
complement research projects from a service user’s point of view, from the quality and clarity of the 
documentation to the feasibility of a patients’ involvement in a study. 
 
Liverpool Heart & Chest Hospital, Research & Innovation Team: to improve the quality, relevance, and focus 
of research and to ensure all the study follows the guidelines set for research by the Department of Health.  
 
 
PROTOCOL CONTRIBUTORS 
The study proposal was reviewed and approved by LJMU's Research Committee.  
 
Details of the study were finalised by collaboration of the supervisory team, and the specific methodology 
was further developed with the participation of the PhD student. The research methods to be used are 
validated and established techniques commonly used in clinical research. 
 
The research team have already met with the Service Users Research Endeavour (SURE) group of the 
Liverpool Heart and Chest Hospital and with the Research and Innovation Committee of the LHCH. Feedback 
was received during both meetings, and the study was approved by the SURE Group and the R&I Committee. 
 
We will continue the work with specific focus groups of patients in CR. The PPI groups will participate and 
feed back on the different aspects of the research. 
 
 
 
 
 
 
 
 

 
 
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STUDY FLOW CHART 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening of patients in LHCH cardiac rehabilitation centres referral database  
Consecutive eligible patients consented 
Stage 1: Cross-sectional analysis (DXA, grip strength, prior NHS 
records) 
SO subjects – 
randomisation to 
intervention groups 
Intervention (12 weeks) 
Data analysis and reporting 
Control – 
standard 
CR 
High 
Protein 
Med diet 
Resistance 
exercise 
HPMD + 
Resistance 
exercise 
Endpoint data collection 
Stage 2: Baseline data collection 

 
 
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ABBREVIATIONS 
 
CI 
Chief Investigator 
GP 
General Practitioner 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
LJMU REG 
LJMU Research Ethics and Governance 
LHCH 
Liverpool Heart & Chest Hospital 
NHS 
National Health Service 
NRES 
National Research Ethics Service 
PIS 
Participant/ Patient Information Sheet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 
CVD 
Cardiovascular disease 
CHD 
Coronary Heart Disease 
CR 
Cardiac Rehabilitation 
CM 
Cardiometabolic 
SO 
Sarcopenic Obesity 
MPS 
Muscle Protein Synthesis 
LBM 
Lean Body Mass 
DXA 
Dual-energy X-ray absorptiometry 
HPMD 
High Protein Mediterranean DIet 
BACPR 
British Association for Cardiac Prevention & Rehabilitation 
1 
BACKGROUND 
Cardiovascular disease (CVD) in the UK is behind 1 in 4 deaths/year (>150,000 people), with coronary heart 
disease (CHD) being the most common type [1]. In addition to the loss of life, the economic cost of CVD is 
considerable; in 2015 healthcare for CVD alone in the UK amounted to £10.9 billion with a further £7.7 billion 
lost from the economy due to productivity loses [2]. 
 
Mortality figures due to CHD have been reduced recently, in part due to increased provision of cardiac 
rehabilitation (CR), a therapeutic approach based on exercise training to improve cardiac function, plus 
advice regarding smoking cessation, dietary changes and weight loss [3]. 
2 
RATIONALE 
Most of the evidence on the benefit of CR examines the links between exercise and CV morbidity and 
mortality [4]; however, there is considerable evidence showing improvements in markers of cardiovascular 
risk through different dietary strategies [5]. Of particular relevance, results from studies on both the primary 

 
 
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and secondary prevention of CVD suggest Mediterranean diet-based approaches are the most adequate to 
treat these patients [6-13].  
 
Obesity, and in particular, visceral adiposity, is associated with cardiometabolic (CM) risk markers (e.g., high 
cholesterol and triglycerides levels, HbA1c, etc.) [14-16], however, an “obesity paradox” appears to exist in 
the cardiac population, where increased mortality has been linked to low body mass index (BMI) [17, 18]. 
However, low lean body mass (LBM) is the likely driver of this phenomenon due to sarcopenia, a progressive 
loss of LBM associated with aging [19]. Patients with a combination of low LBM and abdominal distribution 
of body fat, known as sarcopenic obesity (SO), are at greater risk of CVD, exacerbated in CR [20-23]. Thus, 
increasing relative LBM content, rather than simply promoting weight loss, may be an appropriate target in 
CR patients.  
 
One particular barrier to maintaining or accruing LBM is the presence of anabolic resistance in older adults, 
which can result in a reduced muscle protein synthetic (MPS) response to both exercise and the ingestion of 
currently recommended intakes of protein [24]. Protein intakes above currently recommended levels (1.0-
1.5 g/kg/BW) [25] combined with sufficiently intense resistance training [26] can overcome this anabolic 
resistance and positively influence muscle mass, ultimately leading to greater improvement in body 
composition, when accompanied by a reduction in total body fat mass [27]. 
3 
RESEARCH QUESTION 
We aim to determine the prevalence of sarcopenic obesity in a CR population and how this body composition 
relates to markers of cardiometabolic health. As there is no consensus definition of SO, multiple definitions, 
along with their relationship with CM risk markers, will be investigated. 
 
We aim to investigate to what extent a high-protein Mediterranean-style diet and resistance exercise, alone 
and in combination, can augment LBM. Furthermore, we will ascertain whether the above interventions 
improve markers of cardiometabolic health. 
 
Therefore, we will conduct a feasibility study with embedded pilot to obtain preliminary data on the practical 
and clinical considerations and cost-effectiveness of the proposed interventions, in preparation for an 
appropriately powered randomised controlled trial for increasing lean mass and improving cardiometabolic 
risk markers in patients with SO. 
4 
OBJECTIVES AND OUTCOME MEASURES 
Quantitative research 
 
Objectives 
Outcome Measures  
Timepoint(s) 
of 
evaluation of this 
outcome measure 
(if applicable) 
Primary 
Objective 
To investigate to what extent a high-
protein Mediterranean-style diet and 
resistance exercise, alone and in 
combination, can augment LBM and 
muscle strength 
Increases in LBM will be measured using 
DXA and anthropometry. 
Increases in strength will be measured with 
grip strength dynamometer 
To be performed 
within 1 week prior 
to and within 1 
week 
after 
completion of the 
12 
week 
intervention 
Secondary 
Objectives 
To ascertain whether the above 
intervention improves markers of 
cardiometabolic health. 
Cardiometabolic 
risk 
markers 
(blood 
glucose, lipid profile etc) will be measured 
using 
blood 
samples 
along 
with 
measurements of blood pressure 
Blood pressure will 
be measured in the 
cross-sectional 
stage, and before 

 
 
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and 
after 
the 
intervention 
Blood will be drawn 
1 week prior to and 
1 
week 
after 
completion of the 
12 
week 
intervention 
 
Qualitative research 
 
Aim/Research Questions 
Objectives 
Primary 
To determine the feasibility, practical and clinical 
considerations and cost-effectiveness of the 
proposed interventions, in preparation for an 
appropriately powered randomised controlled 
trial for increasing lean mass and improving 
cardiometabolic risk markers in patients with SO. 
Participants will be asked to provide feedback on: 
- recruitment, 
- tasting of high-protein foods, 
- recipes, appeal of the meals, how they fit with the 
Merseyside culture, 
- involvement and support of other members of the 
family (especially those in charge of purchasing and 
cooking food), 
- familiarity session(s) with resistance training, 
exploring 
ability 
to 
perform 
exercises 
and 
personalising the training system, 
- preferences to undertake resistance exercise (e.g. in 
a supervised or unsupervised setting), 
- preferred follow-up frequency and method (e.g. 
face to face, phone, etc.), 
- issues with dietary and exercise adherence, 
Participants will also: 
- help shape the protocol and ensure the project is 
participant-friendly and sensitive by assisting with 
ethical considerations,  
- discuss research findings and help with lay 
dissemination. 
5 
STUDY DESIGN AND METHODS OF DATA COLLECTION AND DATA ANALYSIS 
 A single-centre, cross-sectional analysis of the prevalence of SO in CR patients followed by a single-centre, 
2x2 factorial, randomised, open label controlled trial. 
5.1 
RANDOMISATION AND BLINDING 

 
 
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All participants will be assigned to their group by computer randomisation by the PhD student. Due to the 
nature of the intervention, blinding will not be possible. 
5.2 
BASELINE ASSESSMENTS 
STAGE 1: Screening and focus group 
To be carried out at LJMU Byrom St campus (L3 3AF) by the PhD student. The visit is expected to last 30 
minutes and will entail: 
i) Assessing body composition. This will be done in three different ways. 
 
Firstly, we will measure participant height using a stadiometer and waist circumference using a tape 
measure.  
 
Secondly, we will use a bioelectrical impedance analysis scale to measure lean body mass, total body 
fat mass and visceral fat mass. 
 
Thirdly, we will perform a DXA (Dual-energy X-ray Absorptiometry) scan for 15-20 minutes which 
allows us to create an image of the distribution of lean body mass and fat mass. 
ii) Taking blood pressure 
 
Following standard protocol, participants will be asked to sit for 5 minutes before we take blood 
pressure; we will measure it three times to ensure an accurate reading.  
iii) Grip strength test 
 
Will be tested using a device that one squeezes as hard as possible (grip strength dynamometer). We 
will do this three times to ensure an accurate reading. 
(iv) Mediterranean Diet Score 
 
Participants will fill in a brief 13-question questionnaire regarding the frequency of their intake of 
certain foods 
 
Participants will also be invited to attend a focus group to share views and opinions about food habits and 
preferences, and about physical activity. This will be carried out at participants community CR centre and will 
take 15-20 minutes 
 
5.3 
INTERVENTIONS (IF APPLICABLE) 
Based on the results from the first visit, approximately 60 patients with lower proportions of muscle mass to 
fat mass will be asked to take part in the diet and exercise intervention, which will last 12 weeks. Participants 
at this stage will be allocated to one of four groups: 1) standard CR; 2) CR plus personalised advice to follow 
a high-protein, healthier diet; 3) CR plus resistance exercise; 4) CR plus diet and resistance exercise.  
 
Personalised dietary advice: if allocated to groups 2 or 4, we will ask participants to make changes to their 
diet to adapt it to a high-protein, Mediterranean-style diet. Research shows that Mediterranean-style diets 
can reduce cardiovascular risk, and although there are different versions of this type of diet, they all have in 
common: 
 
eating more fruit and vegetables, 
 
reducing commercial pastries, and replacing refined carbohydrate foods (white bread, white rice, 
white pasta) by wholegrains (wholegrain bread, rice and pasta), 
 
replacing butter and margarine by olive oil as the main culinary fat, 
 
reducing fatty meat and replacing by lean meat, fish, and legumes (peas, beans, lentils), and by high-
protein, low fat foods, such as low-fat dairy (participants will be provided with 2 high-protein 
yoghurts to eat each day). 
Participants will receive personalised guidance to help follow the new diet in the form of sessions at their 
community CR centre along with guide books and recipe guides. The goal is to make small, easy changes to 
their current eating habits, so the diet will be easy to follow. All foods included will be affordable and easy to 
find in local supermarkets (shopping guides will be provided), and we will provide suggestions and recipes to 
prepare food. 
If allocated to groups 1 or 3, participants will be asked to follow the diet recommendations given during 
phase 3 of CR. 

 
 
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Resistance exercise: if allocated to groups 3 or 4, participants will be asked to perform resistance exercise. 
This involves weights or weight machines aimed at building muscle strength. Participants will be shown how 
to do the exercises by qualified instructors (BACPR cardiac rehabilitation certified) in the community centre 
where they carry out their current phase 3 cardiac rehabilitation. All exercises have been deemed safe for 
cardiac rehabilitation patients and an instructor will be available at all exercise sessions should they need 
assistance. Participants will be required to attend 3 sessions per week and each session is expected to last 
approximately 45 minutes. 
 
If allocated to groups 1 or 2, participants will be asked to continue with the standard, aerobic-style exercise 
(treadmills, rowing machines, elliptical trainers) they have used in phase 3 of CR. This will also require 3 
sessions per week. 
5.4 
SUBSEQUENT VISITS 
ALL stage 2 participants will have to attend two more appointments at LJMU. The second visit will be just 
before beginning the intervention, and the third immediately after completing the intervention. Visits are 
expected to last 45-60 minutes and will entail: 
i) Measures of body composition, blood pressure and grip strength, as described above. 
 
ii) A venous blood sample 
 
We will take about 8 teaspoons of blood. Particpants will need to fast for at least 12 hours prior to 
your appointment (although water is encouraged), as otherwise this may affect the result of the test.  
 
iii) Focus Groups  
 
At the final visit we will also ask about participant experiences with the diet and/or exercise regime 
allocated to them, and to check whether they have experienced any so-called adverse events over 
the study.  
 
iv) Food diaries (prior to lab appointments)  
 
Prior to second and third lab visits, participants will given a template of a four-day food diary, which 
they will need to complete the week before their lab appointment (on three working days plus one 
weekend or festive day, non-consecutive whenever possible), and bring with them on the morning 
of the visit. Participants will be contacted the day before to remind them of their appointment and 
what they must bring. 
 
(v) Mediterranean Diet Score 
 
Participants will fill in a brief 13-question questionnaire regarding the frequency of their intake of 
certain foods 
 
5.5 
STUDY SETTING 
This is a single centre study with all data collection taking place in LJMU, Byrom St. campus. All exercise will 
be carried out at the participants community CR centre, supervised by trained members of the community 
CR program. 
5.6 
STATISTICS AND ANALYSIS 
Cross-sectional study: from the results of body composition analysis, the prevalence of SO will be analysed 
in the sample. Differences in prevalence between genders, and between cardiac conditions (e.g. arrhythmia, 
myocardial infarction, coronary artery disease etc.) will be assessed by Chi-squared tests. We will use Pearson 
or Spearman correlations (according to normality) to study the associations between body composition 
variables, markers of strength and performance, and biomarkers of cardiovascular risk (based on patient data 
requested from LHCH) and multiple regression to assess the predictive capacity of indicators of sarcopenic 
obesity and muscle strength on cardiovascular risk. 

 
 
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Pilot study: comparisons between intervention groups for all outcome measures will be performed by means 
of mixed model ANOVA, to account for inter-subject (differences between treatments) and intra-subject 
(differences between baseline and endpoint) variability. Since a sample size calculation will not be conducted 
for this component, interpretation of the results will be largely descriptive and focused on confidence limits 
around parameter estimates.  
Statistical significance will be set at p<0.05, and all analyses will be conducted using IBM SPSS Statistics v25 
(SPSS Inc., Chicago, IL). 
6 
PARTICIPANT RECRUITMENT 
6.1 
STUDY PARTICIPANTS 
Participants will be recruited from Liverpool Heart & Chest Hospital Cardiac Rehabilitation unit. Participants 
in the cross-sectional study will be admissions to phase 3 CR. Participants in the intervention trial will have 
recently completed phase 3 CR, will have been deemed as cardiac stable, and will be willing to participate in 
phase 4 CR (Activity for Life). The minimum age restriction for participants will be 40-years 
 
For the cross sectional study, sample size has been estimated as n=240, based on a prevalence of SO of 20% 
with 
precision 
at 
5% 
and 
confidence 
at 
95%, 
and 
using 
the 
online 
calculator 
at 
http://sampsize.sourceforge.net/iface/. 
 
The sample size for the feasibility study has been arbitrarily kept small (10-15 participants per intervention 
group) to allow ease of recruitment and management of participants before development into a fully 
powered randomised controlled trial.  
6.2 
INCLUSION CRITERIA 
Stage 1: 
 
Informed consent given 
 
Referral to cardiac rehabilitation program 
 
Ability to attend screening at Liverpool John Moores University 
Stage 2: 
 
Informed consent given 
 
Meeting selected criteria to define sarcopenic obesity (dependent on analysis from stage 1) 
 
Ability to attend screening at Liverpool John Moores University 
 
Cardiac function deemed stable after phase 3 cardiac rehabilitation   
6.3 
EXCLUSION CRITERIA 
 
Inability to perform resistance exercise (determined by primary care team) 
 
Renal dysfunction 
 
Inability/unwillingness to digest/consume dairy products 
 
Admission to CR due to congenital or drug/alcohol-abuse induced cardiac events 
 
Pregnancy 
6.4 
RECRUITMENT TECHNIQUE 
Participants will be approached by members of their clinical care team at LHCH, who will invite them to 
participate and confirm they are willing to be contacted by our research team for more information. Please 
refer to 6.5 for further details. 

 
 
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6.5 
PARTICIPANT IDENTIFICATION 
 
Eligible participants will be recruited from patients recently referred to cardiac rehabilitation (Liverpool Heart 
& Chest Hospital Cardiac Rehabilitation Unit), which is where we will start our study. In collaboration with 
the LHCH Cardiac Rehabilitation Uniteligible participants will first be identified by the clinical care team. 
 
Eligible participants will be approached by members of the Knowsley Community Cardiovascular Services 
team, part of Liverpool Heart & Chest Hospital Cardiac Rehabilitation unit. Participants will be informed of 
the research and provided with a participation information sheet and asked to reply with their interest after 
24 hours. They will then be contacted by the PhD student. 
 
6.6 
SCREENING AND ELIGIBILITY ASSESSMENT 
The maximum period from screening in stage 1 to the recruitment for the intervention (stage 2) will depend 
on the participant’s progression through CR phase 3. As phase 3 normally last 8 weeks, and assuming a 
participant has just started CR phase 3 there may be up to 8 weeks from the first (screening) visit to second 
visit (baseline) measurements. 
6.7 
INFORMED CONSENT 
The participant must personally sign and date the latest approved version of the Informed Consent form 
before any study specific procedures are performed. 
Written and verbal versions of the Participant Information and Informed Consent will be presented to the 
participants detailing 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 wished to consider the information, and the opportunity to 
question the Investigator, their GP or other independent parties to decide whether they will participate in 
the study. Written Informed Consent will then be obtained by means of participant dated signature and dated 
signature of the person who presented and obtained the Informed Consent. The person who obtained the 
consent must be suitably qualified and experienced, and have been authorised to do so by the Chief/Principal 
Investigator. A copy of the signed Informed Consent will be given to the participant. The original signed form 
will be retained at the study site. 
6.8 
DISCONTINUATION/WITHDRAWAL OF PARTICIPANTS FROM STUDY 
Each participant has the right to withdraw from the study at any time.  In addition, the Investigator may 
discontinue a participant from the study at any time if the Investigator considers it necessary for any reason 
including: 
 
Pregnancy 
 
Ineligibility (either arising during the study or retrospectively having been overlooked at screening) 
 
Significant protocol deviation 
 
Significant non-compliance with treatment regimen or study requirements 
 
Withdrawal of Consent 
 
Loss to follow up 
 
Should a participant wish to withdraw from the study, their anonymised data will be retained for 10 years. 
Their data may still be included in the analysis if they withdraw after completing the intervention, and for 
reasons that do not affect the study outcomes. If the participant wants their data to be removed from the 
study, they may contact us and request such. 
 
Withdrawn participants may be replaced should sufficient time and resources be available. 

 
 
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The reason for withdrawal by researcher (and by participant, if this information is volunteered) will be 
recorded in a study file. 
7 
DATA MANAGEMENT 
7.1 
ACCESS TO DATA 
Direct access will be granted to the research team, authorised representatives from the Sponsor and host 
institution for monitoring and/or audit of the study to ensure compliance with regulations. 
7.2 
DATA RECORDING AND RECORD KEEPING 
The information provided as part of the study will be anonymised. We will use codes to label, trace and 
identify your samples, records and questionnaires; we will never use any personal data from which 
participants can be identified, such as name, initials, or date of birth. 
Documents that include personal data (such as the consent form, or your contact details) will be stored on 
password-protected computers and locked filing cabinets at LJMU, accessed only by the research team. They 
will be destroyed upon completion of the study, unless they would like a copy of the final study results; in 
that case, we will retain their names, phone numbers and email addresses, so we can contact them later. The 
results should be available approximately 1 year after the study is completed; participant personal data will 
be then deleted. 
Research data will be stored in databases using the codes as identifiers, never personal data, and they will 
be kept in password-protected computers only accessed by the research team. Samples will be booked into 
a database and receive a laboratory code, with only those involved in the research having access. All data 
and samples will be destroyed after 10 years. 
The names of participants will never be published in any communication of results and findings. 
 
7.3 
SAMPLE HANDLING 
 
Blood samples will be processed and stored according to current UK regulations and rules of good research 
practice (Human Tissue Act 2004), and will be kept for a maximum of 10 years. Briefly, blood samples will be 
processed immediately after collection, and the serum will be stored in a secure freezer in the Life Sciences 
Building at LJMU’s Byrom St campus. All samples will be stored pseudo-anonymously; this means that all 
identifiable information will be removed and replaced by a code to allow the research team to trace the 
samples and match them with the other measurements (body weight, muscle mass measures, etc.). Once all 
participants have completed the intervention, samples will be analysed. Once the specified storage period 
ends, all samples will be disposed of following current UK regulations. 
8 
SAFETY REPORTING  
Adverse Events, Adverse Reactions and Serious Adverse Events will be recorded in the participants 
documentation as they are brought to the attention of the researchers and if necessary will be reported to 
the appropriate authority (LJMU REC, LHCH, participants GP etc.) in accordance with LJMU procedures. 
 
9 
QUALITY ASSURANCE PROCEDURES 
The study may be monitored, or audited in accordance with the current approved protocol, GCP, relevant 
regulations and standard operating procedures OF LJMU. 
10 
ETHICAL AND REGULATORY CONSIDERATIONS 
10.1 DECLARATION OF HELSINKI 

 
 
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The Investigator will ensure that this study is conducted in accordance with the principles of the Declaration 
of Helsinki and relevant regulations 
10.2 ASSESSMENT AND MANAGEMENT OF RISK 
 
Participants will be scanned by a DXA scanner, which will involve use of small doses of ionising radiation, 
though this is a minimal amount compared to other medical imaging techniques, such as standard X-ray and 
CT scans. The DXA scan would be equal to approximately 2 microsieverts (μSv); this is compared to 20 
microsieverts for a chest X-ray and 10,000 microsieverts for a CT scan. It is also less than a transcontinental 
flight (40 μSv) and one day of natural background radiation (8 μSv). 
 
Great care will be taken to ensure vulnerable people (for example, pregnant women) will not be permitted 
to take part, both during the initial screening and recruitment, and also during the scans where mandatory 
exclusion criteria are checked before the scan can begin. 
The study will limit the involvement of each participant to three scans, and they will be fully informed as to 
the exposure they will have, should they choose to participate. The radiation exposure is so low that no 
shielding of the room or of the person conducting the scans is necessary; therefore, the anticipated risk to 
the participant is negligible. 
 
The participants are being asked to be involved in a study which has a central focus on body weight and 
composition, which can be a very sensitive subject. As the participants will be willing volunteers for the study, 
it is expected that only people who are comfortable with this issue will be involved. Additionally, the 
participants can request for their bio-impedance and anthropometric measurements to be taken by a 
member of the research team of the same gender. They can also request a chaperone to be present during 
the procedure. Privacy and confidentially will be ensured when taking measurements, and all data will be 
anonymised upon collection and storage. 
 
In addition, participants will be reminded that they can withdraw and remove themselves from the situation 
(and the study) at any time. 
 
For the DXA scans, questionnaires and anthropometric measurements, it is not anticipated that there will be 
significant inconvenience for those who choose to take part in this project, as their time involvement is 
minimal at 45 minutes per visit, and we will do our best to accommodate their visit times to their preferences 
and availability (within the limits of the research requirements). 
 
Participants will be made aware of the requirements of the dietary intervention while seeking consent, and 
it is expected that those who are comfortable with this dietary change will be involved. The dietary 
intervention will not use difficult to source ingredients and will be tailored to suit the tastes of the 
participants. Various recipes and food substitutions will be provided to participants at the beginning of the 
protocol. The high-protein diet of the protocol would only be potentially detrimental to individuals who have 
renal deficiency, and therefore this is one of the studies exclusion criteria. Participants will also receive 
regular contact from the PhD student regarding their adherence. 
 
Participants will be made aware of the requirements of the exercise intervention while seeking consent, and 
it is expected that those who are comfortable with this change in physical activity will be involved. All 
participants will have received exercise tolerance tests as part of their NHS cardiac rehabilitation and will be 
cleared for the exercise protocol. They will also receive instruction from a collaborator suitably trained in 
exercise for cardiac rehabilitation regarding how to safely complete the exercise protocol. 
 
The involvement of the participants and their data will be kept confidential, with no personal identifying data 
being present on questionnaires, forms or DXA scans. The unique code that can identify a participant will be 
kept on a secure system that can only be accessed by the research team. Therefore it is not expected that 
there will be a significant risk of a confidentiality breach. 

 
 
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Should the participant disclose information indicating a risk of potential harm to themselves or others, the 
appropriate authority will be contacted (LHCH, patient’s GP, police etc,). 
10.3 PARTICIPANT CONFIDENTIALITY 
The data custodian will be the PhD student. All investigators and study site staff must comply with the 
requirements of data protection legislation with regards to the collection, storage, processing and disclosure 
of personal information and will uphold the Act’s core principles.  
 
Information provided as part of the study will be anonymised. We will use codes to label, trace and identify 
samples, records and questionnaires; we will never use any personal data from which participants can be 
identified, such as name, initials, or date of birth. 
 
Documents that include personal data (such as the consent form, or contact details) will be stored on 
password-protected computers and locked filing cabinets at LJMU, accessed only by the research team. They 
will be destroyed upon completion of the study, unless participants would like a copy of the final study 
results; in that case, we will retain their name, phone number and email address, so we can contact them 
later. Their personal data will then be deleted 
 
Research data will be stored in databases using the codes as identifiers, never personal data, and they will 
be kept in password-protected computers only accessed by the research team. Samples will be booked into 
a database and receive a laboratory code, with only those involved in the research having access. All data 
and samples will be destroyed after 10 years. 
 
The names of participants will never be published in any communication of results and findings. 
 
10.4 EXPENSES AND BENEFITS 
Participants will not be reimbursed for travel expenses incurred while participating in the study 
 
Participants in the high protein diet groups will be provided with 2 high-protein yoghurts per day for the 
duration of the trial. 
 
The diet and exercise chosen in this study have been shown to have a number of benefits: 
 
High-protein foods may increase satiety after a meal, reducing hunger. 
 
This may also lead to a lower calorie intake and consequential potential weight loss. 
 
This may lead to a loss of fat mass, improving body composition.  
 
Muscles may grow and become stronger, meaning everyday activities will feel easier. 
 
Blood sugar levels may improve due to healthier muscles helping with blood sugar control. 
 
Blood cholesterol and fats may improve, reducing risk of further cardiac events. 
10.5 OTHER ETHICAL CONSIDERATIONS 
In the unlikely event of finding any abnormalities or anything of clinical significance, the findings will be 
checked by a clinical specialist.  If the specialist feels that the abnormality was medically important, they will 
discuss the implications with the participant and arrange for further investigations as necessary.  Participants 
will not be informed unless the doctor considers the finding has clear implications for their current or future 
health.  It is important to note that data collected are not carried out for diagnostic purposes, and therefore 
the data are not a substitute for a clinical appointment. Rather, the data are intended for research purposes 
only. 
10.6 RESEARCH ETHICS COMMITTEE (REC) AND OTHER REGULATORY REVIEW & REPORTS 

 
 
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 
Before the start of the study, a favourable opinion will be sought from from the UK Health 
Departments Research Ethics Service NHS REC for the study protocol, informed consent forms and 
other relevant documents e.g. advertisements 
 
Approval will be obtained from LJMU REG (and Co-Sponsors) for any amendments to, or changes of 
status in the study prior to submission to the REC that ethically approved the study and any other 
regulatory authorities  
 
All correspondence will be retained. 
 
The protocol, informed consent form, participant information sheet and any proposed advertising 
material will be submitted to the HRA for written approval. 
 
Annual Progress Reports will be submitted to the NHS REC which gave the favourable opinion, the 
HRA (hra.approval@nhs.net) and the Sponsor (Sponsor@ljmu.ac.uk) on the anniversary of NHS REC 
Favourable Opinion, and annually thereafter until the End of Study Declaration has been submitted 
to the NHS REC which gave the favourable opinion, the HRA and the Sponsor 
 
Upon the completion of the study an End of Study Declaration (within 90 days of the end of the study) 
and End of Study Report (within 12 months of the end of the study) will be submitted to the NHS REC 
which gave the favourable opinion and LJMU REG (sponsor@ljmu.ac.uk) 
 
 
Annual Progress Reports will be submitted to the NHS REC which gave the favourable opinion and 
the Sponsor (Sponsor@ljmu.ac.uk) on the anniversary of HRA approval, and annually thereafter until 
the End of Study Declaration has been submitted to the NHS REC which gave the favourable opinion 
and the Sponsor. 
 
Upon the completion of the study an End of Study Declaration (within 90 days of the end of the study) 
and End of Study Report (within 12 months of the end of the study) will be submitted to the NHS REC 
which gave the favourable opinion and LJMU REG (sponsor@ljmu.ac.uk) 
 
Early termination or suspension of the research will be reported to all relevant review bodies and the 
Sponsor (sponsor@ljmu.ac.uk) within 15 days. 
11 
SCIENTIFIC REVIEW 
The study protocol went through successive stages of scientific review: 
1) It was first reviewed and approved for support under the cross-faculty PhD funding scheme. The 
panel reviewing the proposals was formed by staff from the Faculty of Science, Faculty of Education, 
Health and Community, and the Institute of Health Research, LJMU. 
2) The study was subsequently reviewed and approved by the Service Users Research Endeavour (SURE) 
Group of the Liverpool Heart and Chest Hospital. 
3) Finally, our study protocol was presented at and approved by the Research and Innovation 
Committee of the Liverpool Heart and Chest Hospital. 
 
All different stages of review were carried out by independent reviewers, both internal (from LJMU) and 
external (LHCH), meeting the requirements of Level 4 studies. 
 
Level 1 No Peer Review 
Required – minimal risk 
(no patient contact) 
Level 
2 
Review 
by 
project   
 supervisor 
(student projects with 
either 
 no  or 
minor 
patient/participant 
involvement) 
Level 
3 
Review 
by 
departmental 
colleague 
(Low-risk 
projects 
with 
minimal 
patient 
involvement) 
Level 
4 
External, 
independent 
peer 
review 
Short 
questionnaire 
studies for use among 
hospital staff or GPs. 
Human tissue samples 
[anonymous 
to 
investigator] 
Human 
tissue 
samples 
[anonymous 
to 
investigator] 
Clinical 
trial 
of 
an 
investigational medicinal 
product 

 
 
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Questionnaires asking 
patients 
about 
the 
quality 
of 
hospital 
services. 
Study 
administering 
questionnaires 
Study 
administering 
questionnaires 
Clinical trial of a medical 
device 
Use 
of 
data 
from 
medical 
notes 
by 
clinician looking after 
patient. 
Qualitative study 
Qualitative study 
Performance 
Evaluation 
of an in vitro diagnostic 
device 
Study limited to working 
with data 
Study limited to working 
with data 
Other clinical trial or 
clinical investigation 
Non-intimate examination 
techniques, 
e.g. 
blood 
pressure measurement. 
Research Tissue Bank 
Human 
tissue 
(tissue 
samples and data) [newly
obtained, 
identifiable or obtained 
from surplus] 
12 
PATIENT & PUBLIC INVOLVEMENT 
The research team initially liaised with Knowsley Community Cardiovascular Service in charge of phase 4 
cardiac rehabilitation, to gather information relevant to the current practice and support offered to cardiac 
rehabilitation patients after leaving the hospital, as well as this population specific characteristics, needs and 
requirements. 
 
The research team then consulted with the Liverpool Heart & Chest Hospital, Service Users Research 
Endeavour 
(SURE) 
group 
(see 
ROLES 
AND 
RESPONSIBILITIES 
OF 
STUDY 
MANAGEMENT 
COMMITTEES/GROUPS AND INDIVIDUALS on page 7. 
 
The SURE group has already provided advice regarding the participant information documents, and approved 
the study. 
 
We will continue with specific focus groups of patients in CR. The PPI groups will participate and feed back 
on the different aspects of the research (see qualitative research in OBJECTIVES AND OUTCOME MEASURES) 
 
All PPI activities will be recorded and evaluated, with aims to present at conferences and publish in 
appropriate peer reviewed journals.  
13 
PROTOCOL COMPLIANCE  
Protocol adherence will be monitored with weekly phone call with each participant, carried out by the PhD 
student. 
Accidental protocol deviations can happen at any time. They will be adequately documented on the relevant 
forms and reported to the Chief Investigator and Sponsor immediately.  
Deviations from the protocol which are found to frequently recur are not acceptable, will require immediate 
action and could potentially be classified as a serious breach. 
The Investigator may discontinue a participant from the study at any time if the Investigator considers it 
necessary for any reason. Such occurrences will be detailed in the individual participant study logs 
14 
INSURANCE 

 
 
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Table 11.1 
The research study includes the following: 
Please state YES 
or NO to at least 
one. 
treating or preventing disease or diagnosing disease 
YES 
ascertaining the existence degree of or extent of a physiological condition 
YES 
assisting with or altering in any way the process of conception 
NO 
investigating or participating in methods of contraception 
NO 
inducing anaesthesia 
NO 
otherwise preventing or interfering with the normal operation of a physiological 
function 
NO 
None of the above 
NO 
 
Table 11.2 
 
The study is limited to the following activities and will be undertaken in the UK. 
Please state YES 
or NO 
Questionnaires, interviews, psychological activity including CBT 
YES 
Venepuncture (withdrawal of blood) 
YES 
Muscle biopsy 
YES 
Measurements of physiological processes including scanning 
YES 
Collections of body secretions by non-invasive methods 
YES 
Intake of foods or nutrients or variation of diet (other than administration of drugs). 
YES 
 
LJMU has Clinical Trials insurance to cover the legal liability of the University as Research Sponsor in the 
eventuality of harm to a research participant arising from management and design of the research by the 
University and the activities here are included within that coverage. 
 
LJMU’s Clinical Trials insurance policies provide an indemnity to our employees and students for their 
potential liability for harm to participants during the conduct of the research and the activities here are 
included within that coverage. 
15 
CONTRACTS AND AGREEMENTS 
A standard Non-Commercial Model Agreement (mNCA) will be negotiated with Liverpool Heart & Chest 
Hospital 
 
A research passport (letter of access) will be applied for, for the PhD student who will undertake the research 
within the NHS. 
16 
DEFINITION OF END OF STUDY 
The end of study is the date of completion of analysis of samples. 
17 
END OF STUDY AND ARCHIVING 
The end of study is the date of the last visit of the last participant. Relevant consent forms will be obtained 
for each participant, allowing for the samples to be stored and data to be archived for at least 10 years. 
18 
ACCESS TO THE FINAL STUDY DATASET 
Aim: to describe who will have access to the final dataset 
The PhD student, all supervisors and the lead clinician will have access to the full dataset. The study will allow 
site investigators to access the full dataset if a formal request describing their plans is approved by the 

 
 
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steering group. Any secondary analysis will only be undertaken with the consent of the participants. All 
patient documentation will reflect the future use of data in research. 
19 
DISSEMINATION POLICY 
 
All the data from the study will be own and managed by the research team. Experimental data will 
be appropriately coded and stored in a database (MS Excel) – all information in this database will be 
anonymous, and individual data will not be shared, published or disseminated in any way. 
 
Data will be analysed with appropriate statistical tests (according to the nature and amount of the 
data within each variable of study). A final report will be produced to inform all parties involved in 
this study: Liverpool John Moores University, University of Chester, Liverpool Heart and Chest 
Hospital, Knowsley Community Centre, SURE Patient group, and relevant stakeholders (e.g., funders, 
NHS). The report will be shared with the partners via email; it will be communicated using social 
media as well, so that other parties interested can request it. 
 
Data will be analysed as well for presentation in professional conferences (e.g., European and 
International Congress on Obesity, European and International Nutrition Conference, British 
Association for Cardiac Prevention & Rehabilitation Conference etc) and publication in specialised 
journals (e.g., International Journal of Obesity, American Journal of Clinical Nutrition, European 
Journal of Clinical Nutrition, Journal of the American College of Cardiology, Circulation, European 
Heart Journal etc). The research team will be responsible for the authorship and reviewing of the 
conference proceedings and publications. The fully anonymised dataset will be made public at the 
request of journals, or as a requirement by the funding bodies (e.g., LJMU repository). 
 
Current funding from Liverpool John Moores University and the Liverpool Clinical Commissioning 
Group will be acknowledged in all publications, and so will any additional future funding. These 
funding bodies do not request publication or reviewing rights. In the event of collaborating with 
industry sponsors, an agreement will be signed so that the research team retain the rights over data 
property and publication rights. 
 
Participants will be informed of the final results of the study – a lay summary will be produced to 
share the findings with them, and they can receive copy of the final report as well, should they wish. 
Participants can also request a summary report on their personal results, directly to the PI and/or 
the PhD student who will be their main contact throughout the study. 
 
The study protocol will be registered publicly with clinicaltrials.gov 
 
20 
AUTHORSHIP ELIGIBILITY GUIDELINES AND ANY INTENDED USE OF PROFESSIONAL WRITERS 
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 by an LCCG 
RCF grant and any other grants, should application be successful. Authorship will be determined in 
accordance with the ICMJE guidelines and other contributors will be acknowledged.  
21 
REFERENCES 
1. 
British Hear Foundation, BHF CVD FactSheet UK. 
2. 
Wilkins, E., et al., European Cardiovascular Disease Statistics 2017 edition. 2017: Brussels. 
3. 
British Association for Cardiovascular Prevention and Rehabilitation, BACPR Standards and Core 
Components for Cardiovascular Disease Prevention and Rehabilitation. 2017. 
4. 
McMahon, S.R., P.A. Ades, and P.D. Thompson, The role of cardiac rehabilitation in patients with 
heart disease. Trends in Cardiovascular Medicine, 2017. 27(6): p. 420-425. 
5. 
Medina-Remon, A., et al., Dietary patterns and the risk of obesity, type 2 diabetes mellitus, 
cardiovascular diseases, asthma, and neurodegenerative diseases. Critical Reviews in Food Science 
and Nutrition, 2016. 58(2): p. 262-296. 
6. 
Deanfield, J., et al., Joint British Societies' consensus recommendations for the prevention of 
cardiovascular disease (JBS3). Heart, 2014. 100: p. 1-67. 

 
 
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7. 
National Institute for Health Care Excellence, Myocardial infarction: cardiac rehabilitation and 
prevention of further cardiovascular disease, in CG172. 2013. 
8. 
Iestra, J., et al., Lifestyle, Mediterranean diet and survival in European post-myocardial infarction 
patients. European Journal of Cardiovascular Prevention & Rehabilitation, 2006. 13(6): p. 894-900. 
9. 
Panagiotakos, D.B., et al., The Mediterranean and other Dietary Patterns in Secondary 
Cardiovascular Disease Prevention: A Review. Current Vascular Pharmacology, 2016. 14(5): p. 442-
451. 
10. 
Trichopoulou, A., C. Bamia, and D. Trichopoulos, Mediterranean diet and survival among patients 
with coronary heart disease in Greece. Archives of Internal Medicine, 2005. 165(8): p. 929-935. 
11. 
Trichopoulou, A., et al., Modified Mediterranean diet and survival after myocardial infarction: the 
EPIC-Elderly study. European Journal of Epidemiology, 2007. 22(12): p. 871-81. 
12. 
de Lorgeril, M., et al., Mediterranean diet, traditional risk factors, and the rate of cardiovascular 
complications after myocardial infarction - Final report of the Lyon Diet Heart Study. Circulation, 
1999. 99(6): p. 779-785. 
13. 
Estruch, R., et al., Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J 
Med, 2013. 368(14): p. 1279-90. 
14. 
Dansinger, M.L., et al., Comparison of the Atkins, Ornish, Weight watchers, and Zone diets for 
weight loss and heart disease risk reduction. Jama-Journal of the American Medical Association, 
2005. 293(1): p. 43-53. 
15. 
Espeland, M., et al., Reduction in weight and cardiovascular disease risk factors in individuals with 
type 2 diabetes - One-year results of the Look AHEAD trial. Diabetes Care, 2007. 30(6): p. 1374-
1383. 
16. 
Poirier, P., et al., Obesity and cardiovascular disease: Pathophysiology, evaluation, and effect of 
weight loss - An update of the 1997 American Heart Association Scientific Statement on obesity and 
heart disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and 
Metabolism. Circulation, 2006. 113(6): p. 898-918. 
17. 
Lavie, C.J., et al., Body composition and survival in stable coronary heart disease: impact of lean 
mass index and body fat in the "obesity paradox". Journal of the American College of Cardiology, 
2012. 60(15): p. 1374-80. 
18. 
Lavie, C.J., R.V. Milani, and H.O. Ventura, Obesity and Cardiovascular Disease Risk Factor, Paradox, 
and Impact of Weight Loss. Journal of the American College of Cardiology, 2009. 53(21): p. 1925-
1932. 
19. 
Fielding, R.A., et al., Sarcopenia: An Undiagnosed Condition in Older Adults. Current Consensus 
Definition: Prevalence, Etiology, and Consequences. International Working Group on Sarcopenia. 
Journal of the American Medical Directors Association, 2011. 12(4): p. 249-256. 
20. 
Atkins, J.L., et al., Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A 
Population-Based Cohort Study of Older Men. Journal of the American Geriatrics Society, 2014. 
62(2): p. 253-260. 
21. 
Gusmao-Sena, M.H., et al., Association between sarcopenic obesity and cardiovascular risk: where 
are we? Nutrcion Hospitalaria, 2016. 33(5): p. 592. 
22. 
Kim, T.N. and K.M. Choi, The implications of sarcopenia and sarcopenic obesity on cardiometabolic 
disease. Journal of Cellular Biochemistry, 2015. 116(7): p. 1171-8. 
23. 
Ma, J., et al., Mid-adulthood cardiometabolic risk factor profiles of sarcopenic obesity. Obesity 
(Silver Spring), 2016. 24(2): p. 526-34. 
24. 
Morton, R.W., et al., Defining anabolic resistance: implications for delivery of clinical care nutrition. 
Current Opinion in Critical Care, 2018. 24(2): p. 124-130. 
25. 
WHO, Protein and Amino Acid Requirements in Human Nutrition: Report of a Joint WHO/FAO/UNU 
Expert Consultation, in Protein and Amino Acid Requirements in Human Nutrition: Report of a Joint 
Who/Fao/Unu Expert Consultation. 2007. p. 1-270. 
26. 
Bouchonville, M.F. and D.T. Villareal, Sarcopenic obesity: how do we treat it? Current opinion in 
endocrinology, diabetes, and obesity, 2013. 20(5): p. 412-419. 
27. 
Galbreath, M., et al., Effects of Adherence to a Higher Protein Diet on Weight Loss, Markers of 
Health, and Functional Capacity in Older Women Participating in a Resistance-Based Exercise 
Program. Nutrients, 2018. 10(8): p. 20. 

 
 
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22 
APPENDICES 
22.1  APPENDIX 1- REQUIRED DOCUMENTATION 
 
Research protocol or project proposal 
 
Letter from statistician 
 
Summary CV for Chief Investigator (CI) 
 
Participant information sheet (PIS) 
 
Participant consent form 
 
Letters of invitation to participant 
 
GP information sheets or letters 
 
Validated questionnaire 
 
Non-validated questionnaire 
 
Referee's report or other scientific critique report 
 
Summary, synopsis or diagram (flowchart) of protocol in non-technical language 
 
Covering letter on headed paper 
 
Letter from sponsor 
 
Letter from funder 
 
SoECAT  
 
Non-Commercial Model Agreement 
 
Evidence of Sponsor insurance or indemnity  
 
Summary of any applicable exclusions to sponsor insurance  
 
Summary CV for student 
 
Summary CV for supervisor (student research) 
 
MHRA "Notice of No Objection" Letter (Medical Devices) and relevant correspondence 
22.2 APPENDIX 3 – AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes made