A Study of the Roles of the Immune and Inflammatory Systems in Hypertension
Conditions: Hypertension, Inflammation, Vascular Diseases
Sponsor: University of Glasgow

 
 
 
 
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      The InflammaTENSION Study Protocol Version 1.1 18/12/2018  
 
The InflammaTENSION Study  
 
A study of the roles of the immune and inflammatory systems in 
hypertension. 
 
 
 
 
Chief Investigators:  
Professor Tomasz Guzik FRCP, FACP &  Professor Christian Delles MD, 
FRCP, FAHA, FBIHS 
 
 
 
 
 
 
 
This study will be performed according to the Research Governance Framework for Health and 
Community Care (Second edition, 2006) and WORLD MEDICAL ASSOCIATION DECLARATION OF 
HELSINKI Ethical Principles for Medical Research Involving Human Subjects 1964 (as amended). 
Running Title 
InflammaTENSION 
Protocol Version 
1.1 
Date 
18/12/2018 
REC Reference Number: 
 
R&D Reference Number: 
 
 
Sponsor’s Protocol Number: 
 
Sponsor: 
NHS Greater Glasgow and Clyde 
Funder:  
European Research Council; 
Horizon 2020 
British Heart Foundation (CoRE) 
Amendment number 
Date 
Protocol version 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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      The InflammaTENSION Study Protocol Version 1.1 18/12/2018  
Contents 
 
Contacts 
 
 
 
 
 
 
 
 
 
 
 
Protocol Approval  
Abbreviations 
Study Synopsis 
InflammaTENSION Study Flowchart 
Study Schedule of InflammaTENSION Study 
Introduction 
 
1:1  
Background 
 
1.2 
 Rationale 
 
1.3  
Prior experience of intervention in cardiovascular disease 
 
1.4  
Study Hypothesis 
Study Objectives 
Study Design 
 
3.1 
 Population 
 
3.2 
 Inclusion Criteria 
 
3.3  
 Exclusion Criteria 
 
3.4 
 Identification of Participants and Consent 
 
 
 
3.4.1 
Participant Identification 
 
 
 
3.4.2 
Participant Registration 
 
 
 
3.4.3  
Consent at Baseline Visit 
 
3.5 
Withdrawal of subjects 
 
 
 
3.5.1 Voluntary Participant Withdrawal 
 
 
 
3.5.2 Investigator withdrawal of patients from EC arm 
 
 
 
3.5.3 Replacement of Withdrawn Participants 
Study Schedule and Trial Procedures 
 
4.1  
Recruitment 
 
4.2  
Registration 
 
4.3 
Study Visit Information 
 
4.4  
Study Schedule and Trial Procedures 
4.5 
Study Outcome Measures 
 
 
 
4.5.1 
Primary Outcome Measure 
 
4.5.2  
Secondary Outcome Measure 
 
4.5 
Incidental Findings Procedure 
 
 
Statistics and Data Analysis Plan  
 
6.1  
Statistical Analysis Plan 
 
6.2 
Sample Size  
 
 
6.3 
Management and Delivery 

 
 
 
 
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7. Study Closure or Definition of End of Trial 
Data Handling 
8.1 
Case Report Forms/Electronic Data Record 
 
8.2 
Record Retention 
Protocol Amendments 
Ethical Considerations 
Insurance and Indemnity 
Funding 
Dissemination of Findings 
References 
 
 

 
 
 
 
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      The InflammaTENSION Study Protocol Version 1.1 18/12/2018  
Contacts 
 
Chief Investigator 
Professor Tomasz Guzik  
 
 
Professor (Institute of Cardiovascular and Medical Sciences) 
 
 
0141 3307590 
tomasz.guzik@glasgow.ac.uk 
 
Co-Investigator  
Professor Christian Delles  
 
 
Professor (Institute of Cardiovascular and Medical Sciences) 
 
 
0141 3302749 
christian.delles@glasgow.ac.uk 
 
Co-Investigator Doctor Eleanor C Murray 
                                        Clinical Research Fellow (Institute of Cardiovascular and Medial Sciences) 
                                        07825829526 
                                        EleanorMurray@doctors.org.uk 
 
Trials Manager  
Dr Katriona Brooksbank 
 
 
Clinical Trials Manager (Institute of Cardiovascular and Medical Sciences) 
 
 
0141 3302627 
katriona.brooksbank@glasgow.ac.uk 
 
 
 
 
Sponsor 
 
NHS Greater Glasgow & Clyde 
Sponsor’s  
Representative  
Dr Maureen Travers 
Research Co-ordinator 
NHS Greater Glasgow & Clyde 
Research and Development Management Office 
West Glasgow Ambulatroy Care Hospital 
G3 8SJ 
 
0141 232 1813 
maureen.travers@ggc.scot.nhs.uk 
 
Funding Body  
European Research Council  
 
 

 
 
 
 
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      The InflammaTENSION Study Protocol Version 1.1 18/12/2018  
 
Protocol Approval 
The InflammaTENSION Study 
A study of the roles of the immune and inflammatory systems in hypertension. 
 
 
 
Sponsor’s Representative  
Dr Maureen Travers 
Research Co-ordinator 
NHS Greater Glasgow & Clyde 
Research and Development Management Office 
West Glasgow Ambulatroy Care Hospital 
G3 8SJ 
01412321813 
maureen.travers@ggc.scot.nhs.uk 
 
 
Signature: 
 
Date: 
 
 
 
Chief Investigator: 
Professor Tomasz J Guzik  
Regius Professor (Institute of Cardiovascular and Medical Sciences) 
BHF Centre of Excellence,  
Institute of Cardiovascular & Medical Sciences, 
University of Glasgow, 
126 University Place 
G12 8TA 
0141 3307590 
tomasz.guzik@glasgow.ac.uk 
 
Signature: 
 
Date: 
 

 
 
 
 
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Abbreviations 
 
ABPM 
 
Ambulatory Blood Pressure Monitoring 
CIMT 
 
Carotid intima-media thickness  
CRF  
 
Glasgow Clinical Research Facility  
BHF 
 
British Heart Foundation 
DSS  
 
Digital Symbol Substitution  
EC  
 
Electronic Cigarettes 
EQ-5D  
 
European Quality of Life-5 Dimensions 
FMD 
 
Flow Mediated Dilation 
GM/HC 
 
General Medicine/Hypertension Clinic (Queen Elizabeth University Hospital) 
GWAS 
 
Genome wide association study 
GP 
 
General Practice 
HTN 
 
Hypertension 
IDQ  
 
the Interheart Diet Questionnaire 
IPAQ                     
the International Physical Activity Questionnaire 
InflammaTENSION 
A study of the roles of the immune and inflammatory systems in 
hypertension. 
MCQ 
 
the Mild Cognitive Impairment Questionnaire 
MoCA  
 
Montreal Cognitive Assessment  
NHSGGC 
 
NHS Greater Glasgow and Clyde 
PFTs 
 
Pulmonary Function Tests 
PIL 
 
Participant information leaflet 
QEUH  
 
Queen Elizabeth University Hospital 
RCT 
 
Randomised Controlled Trial 
 
 
 
 

 
 
 
 
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      The InflammaTENSION Study Protocol Version 1.1 18/12/2018  
 
Study Synopsis 
Title of Study: 
A study of the roles of the immune and inflammatory systems in hypertension. (InflammaTENSION Study).  
Study Centre: 
Institute of Cardiovascular and Medical Sciences 
Duration of Study: 
36 months 
Primary Objective: 
To define the cytokine and cellular immune signature of primary hypertension.  
Methodology: 
Cross sectional clinical/laboratory study. 
Secondary Objectives: 
 
To define the relationships and predictive value of the immune signature of hypertension and clinical phenotypes of hypertension  
 Predictive value of immune signature for blood pressure parameters measured by ambulatory blood pressure measurements 
(ABPM) 
 Predictive value of immune signature for endothelial function assessed by Endo-PAT2000 and flow mediated dilatation (FMD) both 
complementary non-invasive techniques.  
 Predictive value of immune signature for vascular stiffness and central pressure assessed by SphygmoCor 
 Predictive value of immune signature for renal function parameters 
 Predictive value of immune signature for cognitive function  
 
To define genetic determinants of immune signature of hypertension.  
Primary Endpoint: 
Cytokine and cellular immune signature of primary hypertension evaluated by association between hypertensive status (assessed by ABPM) and 
immune signature (analysed as a whole as well as individual pro- and anti- inflammatory cytokine levels and discreet immune cell populations). 
Rationale: 
Experimental data show the presence of immune and inflammatory systems dysregulation in hypertension.  Understanding of the inflammatory 
and immune nature of hypertension is currently based on studies in rodent models of hypertension, but is supported by human epidemiological 
and genome wide association studies (GWAS) studies. It is now essential to identify key checkpoints and inflammatory mechanism(s) involved in 
human hypertension in comprehensive and sufficiently powered studies, which will then be able to guide subsequent in-depth hypothesis-driven 
mechanistic studies. This approach may provide the basis for future randomized clinical trials (RCTs).  
Methodology: 
Cross sectional clinical/laboratory study of 120 primary hypertensive and 120 age, sex and BMI matched - controls 
Cardio renal studies/investigations as well as cognitive dysfunction assessment will be performed during 1 or 2 visits depending on recent ABPM 
availability and patient preference 
Sample Size: 
120 hypertensive 
120 controls 

 
 
 
 
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Screening: 
Initial Screening by the clinical care team at a routine outpatient appointment with subsequent verification by a member of InflammaTENSION 
team (who are also member of the clinical care team for hypertensive patients).  
Registration/Randomisation: 
No randomization 
Main Inclusion Criteria: 
Age between 18-50 years  
Cases: Office blood pressure ≥140 and ≥90 
Controls:   Office blood pressure <140 and <90 and age, sex and BMI matching to cases  
Main Exclusion Criteria: 
(a) Age >50 years old;  
(b) Secondary hypertension (including e.g. adrenal tumours, pheochromocytoma, renal artery stenosis; thyroid disease) 
(c) Acute inflammatory disorders incl. flu, rhinitis, sinusitis etc. within 3 weeks; hospitalization within the past 3 months; Life expectancy of < 3 
years; History of alcohol/substance abuse  
(d) Allergic disorders; chronic infections, COPD, tuberculosis; hepatitis B or C; pneumonitis, bronchiectasis; pericardial or pleural effusion, ascites; 
liver disease;  
(e) Chronic inflammatory/autoimmune conditions such (e.g. SLE, rheumatoid arthritis, ulcerative colitis/Crohn's disease; non-basal cell malignancy 
or myelo- or lymphoproliferative disease within the past 5 years; known HIV+; Immunizations (3 months); pulmonary hypertension;  
(f) Pregnancy, nursing;  
(g) History of symptomatic coronary artery disease (events) or heart failure;  
(h) BMI>35, diabetes/glucose intolerance (fasting glucose, HbA1; testing, glucose challenge where indicated);  
(i) Known albuminuria/microalbuminuria; GFR<60mL/min/1.73m2.  
(j) Any chronic concurrent treatment. Use of systemic or local steroids/immunosuppressive agents (within 6 months) of the inclusion; Current 
(within past 3 months) use of anti-hypertensive medication; 
(k) Major depressive illness or other psychiatric conditions. 
(l) Participants who decline participation in the study or who are unable to provide informed consent 
Product, Dose, Modes of 
Administration:  
N/A 
Duration of Treatment: 
N/A 
Statistical Analysis: 
Institute of Cardiovascular and Medical Sciences; University of Glasgow (Dr John McClure) 

 
 
 
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InflammaTENSION Study Flowchart 
Figure 1: InflammaTENSION Study Flowchart 
 
Outpatient departments, 
Secondary care 
Identification at routine 
appointments 
Hypertensive 
N=120 
 
Baseline visit at the Clinical 
Research Facility (CRF): 
ABPM if not done in last 3 months 
Visit 1 at the CRF for phenotyping 
studies 
Participating Primary care 
Practice, 
Identification at routine 
appointments 
Community screening of 
interested individuals 
Controls   
Age/sex/BMI matched 
N=120 
Recruitment 
Follow up letter 
drop/email/telephone 
Exclusion Criteria 
Identified; 
• 
Secondary cause of 
Hypertension 
• 
Need for immediate 
treatment or urgent 
referral 

 
 
 
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Study Schedule of InflammaTENSION Study 
Table 1: Study Schedule of InflammaTENSION Study 
 
Study Schedule 
Procedure Details 
Recruitment 
Clinical care team at a routine outpatient appointment  /  Letter Drop/ traditional and social media/ SHARE registry/ word of mouth/ referral from 
colleagues 
Registration 
Contact InflammaTENSION investigator; if ABPM is available within past 3 months - patient will be able to choose preference for combined or 
separate Baseline visit and Visit 1. 
Baseline Visit at CRF 
(Visit 0) 
Explanation of InflammaTENSION Study 
Answering of Participant Questions 
Detailed Inclusion and Exclusion Criteria 
Consent 
 
Study Procedures 
(Please refer to The InflammaTENSION Study: Manual of 
Procedures for more details regarding the study procedures) 
Demographic History 
Medical History 
Height and Weight 
Urine Sample 
Heart Rate,  
Office Blood Pressure measurement – 3 times following 5 minutes of rest 
Venous Blood Sample (40ml) for Blood Tests and Immune 
signature/Biomarker analysis 
Venous Blood Sample (10ml) for storage for subsequent genetic analysis 
Ambulatory Blood Pressure Monitor Installation if no ABPM performed within 
past 3 months 
Subjects will be given an IDQ  questionnaire (The Interheart Diet 
Questionnaire)  to be returned during visit 1 
 

 
 
 
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Booking of Visit 
Appointments 
Following Baseline Visit, visit 1 appointment will be booked 
if not planned together with Baseline Visit. 
The InflammaTENSION investigator will liaise with each 
participant to arrange an appointment times, 
Booking of Visit 1  
(0-72 hours post Baseline Visit) 
Establishing preferred contact route 
(email/letter) for follow up letter 
drop and Final Telephone Visit (3.5 
months +/- 14 days following Visit 
1) 
Visit 1 
0-72h post Baseline Visit 
Study Procedures 
(Please refer to The InflammaTENSION Study: Manual of 
Procedures for more details regarding the study procedures) 
This visit will take approximately 2-3.5 The following study procedures will be 
performed at the final visit.   
Questionnaires 
 MCQ  
The Mild Cognitive Impairment Questionnaire 
 MoCA  
Montreal Cognitive Assessment  
 DSS   
Digital Symbol Substitution 
 IPAQ  
The International Physical Activity Questionnaire  
ABPM monitor will be returned 
Carotid Intima-Media Thickness 
Flow Mediated Dilation of Brachial Artery 
Endo-PAT2000 
Sphygmocor study 
Letter Drop/ 
Telephone Visit 
(3.5 months +/- 14 days 
from Baseline Visit) 
Study Procedures 
(Please refer to The InflammaTENSION Study: Manual of 
Procedures for more details regarding the study procedures) 
 
Letter sent containing questionnaire regarding changes in medical 
history since Visit 1 and offering telephone contact from 
InflammaTENSION investigator. 
 
Obtaining information on participant health status changes; changes in 
demographics; changes in medical history 
 
Verification if any cause for secondary hypertension has been identified.  

 
 
 
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1. Introduction 
 
The InflammaTENSION Study  
A study of the roles of the immune and inflammatory systems in hypertension. 
1.1 
Background 
The overarching theme of the proposal Hypertension is a common disease impacting 1 billion people 
worldwide, which leads to catastrophic cardiovascular complications, including heart failure, dementia, 
myocardial infarction and stroke - all of which carry a severe socioeconomic burden. In spite of many years of 
research, the cause of primary hypertension remains unknown and this disease is uncontrolled in a large 
proportion of patients. By interrogating the key hypothesis that inflammatory dysregulation fundamentally 
controls development of hypertension and vascular remodelling, InflammaTENSION provides a new 
paradigm for the management of the disease, with the potential to lead to the identification of novel 
therapeutic targets to control blood pressure and limit target organ damage. InflammaTENSION will result in 
the discovery of novel biomarkers, which may identify patients who could benefit from such immune targeted 
therapies. Importantly, we already made the seminal observation that the immune system not only mediates 
target organ damage, but defines the roles of pro-inflammatory T cells, monocytes, as well as anti-
inflammatory T regulatory cells in the disease process1-4.  However, our current knowledge remains very 
fragmented and so far has not been applied to human pathology. InflammaTENSION will for the first time 
advance the knowledge procured in rodent models into human studies. By combining clinical translational and 
model mechanistic studies it will identify novel inflammatory factors that can control immune mechanisms of 
hypertension. In detail, over the course of the programme we will:  (1) characterize the immunophenotypic 
signature of human hypertension; (2) define key concepts in cytokine biology of hypertension and (3) 
understand how chronic cytokines implicated in hypertension regulate the T cell dependent mechanisms of 
hypertension. InflammaTENSION will also go beyond current state-of-the-art diagnostic methods,with 
comprehensive combination of immunology and cardiovascular disease to create a new understanding of how 
the immune system may lead to human hypertension and vascular remodelling. Such a coordinated and 
integrative programme to better understand the role of dysregulation of the immune system in human 
hypertension will have major impact on the field, enabling translation of these exciting findings to clinical 
practice. 
Unmet need to be investigated: There is an urgent need for a better understanding of the mechanisms of 
hypertension (HTN), as it remains a major cause of death and disability in Europe and worldwide and the 
prediction is that its prevalence will increase by 60% over the next 25 years. The disease affects 30% of 
adults, with an additional 30% considered at high risk of hypertension1. Its prevalence increases with age with 
70% of adults older than 70 being afflicted with this disease. Thus within the ageing society, the 
socioeconomic consequences are particularly marked5, with many elderly patients developing severe 
cardiovascular complications such as heart failure, stroke, myocardial infarction, vascular dementia and renal 
failure. Drug therapy for hypertension improved dramatically between 1975 and 1985, with the addition of 
angiotensin receptor antagonists, angiotensin converting enzyme (ACE) inhibitors and calcium channel 
blockers.  Since the mid-1980s, however, no new classes of drugs have been successfully introduced to treat 
hypertension.  This is unfortunate, because up to 40% continue to have elevated blood pressure despite the 
use of multiple antihypertensive agents. While partially related to poor treatment compliance, this highlights 

 
 
 
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      The InflammaTENSION Study Protocol Version 1.1 18/12/2018  
our insufficient understanding of the underlying mechanisms of this disease. While some cases of 
hypertension are due to single gene mutations6, or underlying correctable causes such as renal artery 
stenosis, pheochromocytoma or adrenal adenoma7, these are uncommon and the cause of the majority of 
cases of adult hypertension are unknown. In these cases, neurohumoral factors such as angiotensin II play 
key roles, as drugs interfering with this pathway are anti-hypertensive. Systemic vascular resistance is 
generally elevated in hypertension8-10, and vasodilators lower blood pressure, which would suggest that 
hypertension, is a vascular disease.  In contrast, the genetic disorders causing hypertension often affect 
sodium transport in the distal nephron6. Therefore we would like to assess genetic difference in cytokine and 
chemokines in the study cases and controls. Transplant of kidneys lacking the angiotensin II AT1a receptor 
into wild-type mice causes resistance to angiotensin II-induced hypertension11 and diuretics are effective anti-
hypertensive agents12, which in turn suggests that the kidney is a major cause of high blood pressure.  Finally, 
there is ample evidence that the central nervous system, and in particular the circumventricular organs 
surrounding the third ventricle, play a critical role in hypertension13. These seemingly disparate roles of the 
vasculature, the kidney and the CNS make the aetiology of hypertension very difficult to comprehend. 
Importantly, we have made an observation that helps link the vasculature, the kidney and the CNS in the 
genesis of hypertension, as all appear to be related to a common inflammatory mechanism. These studies 
have initiated a new research area, which over the past few years has led to the better understanding of 
inflammation in hypertension. 
While the evidence for the role of immune mechanisms in hypertension has been obtained primarily in rodent 
models, epidemiological and genetic evidence strongly supports this. Blood pressure increases with the 
quartile of C-reactive protein14,15 and cytokine levels such as TNF- and IL-6 are consistently increased in 
hypertension16-18, and may convey risk of developing the disease16. Hypertension is highly prevalent in 
immune mediated diseases such as rheumatoid arthritis or psoriasis19, 20. A recent small study has shown an 
increase of senescent CD8+T cells (CD28null) in peripheral blood and target organs in human hypertension21. 
The T cell modulating agent, mycophenolate mofetil, as well as anti-TNF-α treatments lower blood pressure 
not only in rodents22,23, but also in humans24, suggesting that immune targeted interventions may pose a 
feasible future approach, if we are able to identify its mechanisms. Importantly, both GWAS studies25 and 
gene expression signatures of hypertension26 strongly point towards the role of the immune system and 
inflammation. SH2B3/LNK gene encoding T cell activation modulator is a top key driver of hypertension in 
recent systems biology analysis25. 
1.2 
Rationale 
Understanding of the inflammatory and immune nature of hypertension is currently based on studies in rodent 
models of hypertension, but is supported by human epidemiological and GWAS studies. It is now essential to 
identify key checkpoints and mechanisms of inflammatory mechanism(s) of human hypertension in 
comprehensive and sufficiently powered studies, which will then be able to guide subsequent in-depth 
hypothesis-driven mechanistic studies. This approach may provide the basis for future randomized clinical 
trials (RCTs). 
By interrogating the key hypothesis that inflammatory dysregulation fundamentally controls development of 
hypertension and vascular remodelling, InflammaTENSION provides a new paradigm for the management of 
the disease, with the potential to lead to the identification of novel therapeutic targets to control blood pressure 

 
 
 
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      The InflammaTENSION Study Protocol Version 1.1 18/12/2018  
and limit target organ damage.   
We hypothesize that primary hypertension is associated with distinct pattern of changes within 
immune/inflammatory systems consisting of cytokines/chemokines and individual immune cell populations.   
The data generated from the InflammaTENSION study will be invaluable for identification of novel biomarkers 
and therapeutic targets in hypertension.  
Biomarker analysis will be carried out using standard laboratory techniques for cytokines and chemokines as 
follows; 
Luminex (Invitrogen Cytokine/Chemokine/Growth Factor 45-Plex Human ProcartaPlex™ Panel 1 
Target List: BDNF; Eotaxin/CCL11; EGF; FGF-2; GM-
CSF; GRO alpha/CXCL1; HGF; NGF beta; LIF; IFN alpha; IFN gamma; IL-1 beta; IL-1 alpha; IL-1RA; IL-2; IL-
4; IL-5; IL-6; IL-7; IL-8/CXCL8; IL-9; IL-10; IL-12 p70; IL-13; IL-15; IL-17A; IL-18; IL-21; IL-22; IL-23; IL-27; IL-
31; IP-10/CXCL10; MCP-1/CCL2; MIP-1 alpha/CCL3; MIP-1 beta/CCL4; RANTES/CCL5; SDF-
1 alpha/CXCL12; TNF alpha; TNF beta/LTA; PDGF-BB; PLGF; SCF; VEGF-A; VEGF-D 
 
O-Link:Proseek® Multiplex Inflammation I96×96 is a high-
throughput, multiplex immunoassay enabling analysis of 92 inflammation-
related protein biomarkers across 96 samples simultaneously. This high level of multiplexing is achieved witho
ut any compromise on data quality, thanks to our proprietary Proximity Extension Assay (PEA) technology 
 
 
If the data generated from such a trial demonstrate that hypertension has a very distinct immune signature – it 
can be used to stratify patients for future therapies and may provide proof-of-concept for immune targeted 
therapies thus leading to the development of long term studies.  
 
1.3 
Prior Experience of Intervention in Cardiovascular Disease  
In a small pilot study published in July 2016 we were able to identify that hypertension is associated with key 
changes of memory T cells and with changes of immune factors (IL-17, IFN-g)27. This justifies performing a 
comprehensive investigation to identify detailed immune signature of hypertension.  
1.4 
Study hypothesis 
We hypothesize that primary hypertension is associated with distinct pattern of changes within 
immune/inflammatory systems consisting of cytokines/chemokines and individual immune cell populations 
and that this immune signature corresponds with vascular, renal or cognitive phenotypes of hypertension. 
 
 

 
 
 
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2. Study Objectives 
 
The InflammaTENSION pilot study is an observational study aiming to define the cytokine and cellular immune 
signature of primary hypertension. 
 
 
Primary Endpoint 
Cytokine and cellular immune signature of primary hypertension 
 
 
Secondary Endpoints 
1. Relationships and predictive value of the immune signature of hypertension and clinical phenotypes of 
hypertension  
2. To define genetic determinants of immune signature of hypertension which could be used for future 
mendelian randomization studies. 
 
 
 
 
 Predictive value of immune signature for blood pressure parameters measured by ambulatory blood 
pressure measurements (ABPM) 
 Predictive value of immune signature for endothelial function assessed by Endo-PAT2000 and flow 
mediated dilatation (FMD) both complementary non-invasive techniques.  
 Predictive value of immune signature for vascular stiffness and central pressure assessed by 
Sphygmocor 
 Predictive value of immune signature for renal function parameters 
 Predictive value of immune signature for cognitive function 

 
 
 
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3. Study Design 
 
The InflammaTENSION study will be performed according to the Research Governance Framework for Health and 
Community Care (Second edition, 2006). 
3.1 
Study Population 
120 hypertensive subjects and 120 controls will be recruited into the trial (both male and female). 
 
3.2        Inclusion criteria 
 Age between 18-50 years  
 Cases: Office blood pressure ≥140 and ≥90. 
Controls:   Office blood pressure <140 and <90 and age, sex and BMI patching to cases  
3.3 
Exclusion criteria 
(a) Age >50 years old;  
(b) Secondary hypertension (including e.g. adrenal tumours, pheochromocytoma, renal artery stenosis; thyroid 
disease) 
(c) Acute inflammatory disorders incl. flu, rhinitis, sinusitis etc. within 3 weeks; hospitalization with an 
inflammatory condition within the past 3 months; Life expectancy of < 3 years; History of alcohol/substance 
abuse  
(d) Allergic disorders; chronic infections, COPD, tuberculosis; hepatitis B or C; pneumonitis, bronchiectasis; 
pericardial or pleural effusion, ascites; liver disease;  
(e) Chronic inflammatory/autoimmune conditions such (e.g. SLE, rheumatoid arthritis, ulcerative colitis/Crohn's 
disease; non-basal cell malignancy or myelo- or lymphoproliferative disease within the past 5 years; known 
HIV+; Immunizations (3 months); pulmonary hypertension;  
(f) Pregnancy, nursing;  
(g) History of symptomatic coronary artery disease (events) or heart failure;  
(h) BMI>35, diabetes/glucose intolerance (fasting glucose, HbA1; testing, glucose challenge where indicated);  
(i) Known albuminuria/microalbuminuria; GFR<60mL/min/1.73m2.  
(j) Any chronic concurrent treatment. Use of systemic or local steroids/immunosuppressive agents (within 6 
months) of the inclusion; current (within past 3 months) use of anti-hypertensive medication; 
(k) Major depressive illness or other psychiatric conditions. 
(l) Participants who decline participation in the study or who are unable to provide informed consent 
3.4 
Identification of Participants and Consent 
3.4.1. Participant Identification  
Participants will be identified through:  
 
Potential participants will be identified by members of the direct clinical hypertension care team at QEUH 
Glasgow Blood Pressure Clinic (where PI – Prof Guzik and Prof Delles are part of the team), supported by the 
research nurse team 

 
 
 
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 
Other secondary care routine out-patient appointments where potential participants and controls can be 
identified and invited to participate. 
 
Participants may also be identified though SHARE, primary and secondary care data bases and direct 
identification of potential participants through the SPCRN/GGC primary care team.  
 
Potential participants for the age/sex/BMI matched control group will be identified by a member of the direct 
clinical pre-OP orthopaedics care team (from among subjects with planned minor surgeries (e.g. arthroscopy), 
supported by the research nurse team 
 
Potential participants may also be identified through traditional and social media including newspaper 
advertisement, press release, posters in NHS and public sites as well as word of mouth and referral from 
colleagues. 
 
Potential participants will be approached in one of two ways: 1) approach in person by the clinical care team at a 
routine outpatient appointment.  Those who demonstrate interest will be given the patient information leaflet (PIL) 
and asked for verbal consent for their details to be passed to the research team. The PIL will contain a contact 
email address and telephone number to allow patients to “opt in” to the study or get in contact for further 
information.  If there has been no contact from a patient 48 hours after being given the PIL, the patient will be 
telephoned by the clinical fellow or research nurse to ascertain interest in participation in the study; 2) letter drop: 
letters posted to the patient by the principal investigator with information about the study.  The same contact 
information will be provided for patients contacted by letter drop to allow them to opt in to the study.  These 
patients will also be contacted 5-7 days after posting the letter by the clinical fellow to assess interest in 
participating in the study.   
Interested participants will be able to register their interest by contacting the InflammaTENSION investigators 
by: 
o 
Email 
o 
Telephone 
o 
Posting the attached reply slip in the prepaid envelope  
Both the poster and letters will contain contact registration details: 
 
Study specific email address:gg-uhb.inflammatension@nhs.net 
 
InflammaTENSION investigator study specific mobile number:  
 
InflammaTENSION investigator telephone number: 0141 330 7590 
 
 
3.4.2. Participant Registration 
The telephone registration process will include: 
 
Obtaining participants contact details: Name, Date of Birth, Address, Telephone Number and Email  
 
Explanation of the study 
 
Initial Eligibility Screen (with particular focus on verification of lack of known exclusion criteria) 
 
Ineligible participants will be asked if they would like a referral to Glasgow Blood Pressure Clinic, 
QEUH. 
 
Eligible participants will be invited for a baseline visit, and an appointment date and time will be made, a 
participant information leaflet (PIL) will be sent via post or email; depending on the participants’ preference.  
 

 
 
 
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3.4.3. Consent at Baseline Visit 
All participants will have to provide written consent to take part in the study, the consent taken will be inclusive for the 
InflammaTENSION study and must be obtained before any of the study procedures can commence. All participants 
will be provided with a signed copy of their consent form. . 
The Chief Investigator (PI) will retain overall responsibility for the informed consent of participants and will ensure that 
any person delegated responsibility to participate in the informed consent process is duly authorized, trained and 
competent to participate according to the ethically approved protocol, principles of Good Clinical Practice (GCP) and 
Declaration of Helsinki.  
Informed consent will be obtained prior to the participant undergoing procedures that are specifically for the purposes 
of the study and are out-with standard routine care. 
The right of a participant to refuse participation without giving reasons will be respected.   
Before consent is taken the InflammaTENSION investigator will: 
 
Ensure that the participant has read the PIL and has had ≥ 24 hours to reflect upon the information 
 
Explain the study to the participant  
 
Go through detailed inclusion and exclusion criteria for the study** 
 
Answer any of their questions relating to the study  
 
Explain that participation in the study is entirely voluntary and they do not have any obligation to take part in 
the study and they can leave the study at any point*** 
The process of consent will involve: 
 
a discussion between the potential participant and an individual knowledgeable about the research about 
the nature and objectives of the trial and possible risks associated with their participation 
 
the presentation of written material (e.g., information leaflet and consent document which must be approved 
by the REC and be in compliance with GCP, local regulatory requirements and legal requirements) 
 
the opportunity for potential participants to ask questions 
 
Assessment of capacity: for consent to be ethical and valid in law, participants must be capable of giving 
consent for themselves. A capable person will:  
o 
understand the purpose and nature of the research  
o 
understand what the research involves, its benefits (or lack of benefits), risks and burdens  
o 
understand the alternatives to taking part  
o 
be able to retain the information long enough to make an effective decision 
o 
be able to make a free choice  
o 
be capable of making this particular decision at the time it needs to be made (although their capacity 
may fluctuate, and they may be capable of making some decisions but not others depending on their 
complexity) 
o 
where participants are capable of consenting for themselves but are particularly susceptible to 
coercion, it is important to explain how their interests will be protected 
A person is assumed to have the mental capacity to make a decision unless it is shown to be absent. Mental capacity 
is considered to be lacking if, in a specific circumstance, a person is unable to make a decision for him or herself 
because of impairment or a disturbance in the functioning of their mind or brain. In practice for participants with mental 

 
 
 
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incapacity this means that they should not be included in clinical trials if the same results can be obtained using 
persons capable of giving consent and should only be included where there are grounds for expecting that their taking 
part will be of direct benefit to that participant, thereby outweighing the risks.  
 
3.5 
Withdrawal of Subjects 
The participant will remain free to withdraw at any time from the trial without giving reasons and without prejudicing 
his/her further treatment and will be provided with a contact point where he/she may obtain further information about 
the study and where they can receive further needed care. Patient’s withdrawn and needing clinical care will be 
referred for a visit to Glasgow Blood Pressure Clinic at QEUH. Referrals to Glasgow Blood Pressure Clinic will be a 
written letter and participants will be directed to NHSGGC Prof Guzik/Prof Delles led clinic.  
Where a participant is required to re-consent or new information is required to be provided to a participant, the PI will 
ensure this is done in a timely manner.  
The investigator can withdraw participants from the study in the event of inter-current illness or identification of a 
secondary cause for hypertension. Participants who withdraw from the study will be replaced with additional 
participants until 120 participants/arm have attended the final study visit.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
**Verbal consent will be obtained from the participants prior to eligibility screening and/or referral to NHSGGC to 
QEUH General Medicine/Hypertension Clinic 
 
***Participants who are either ineligible or no longer wish to take part in the study will be asked if they would like a 
referral to QEUH General Medicine/Hypertension Clinic for further diagnosis and treatment, and they will be provided 
with the contact details for QEUH General Medicine/Hypertension Clinic. Referrals to QEUH Glasgow Hypertension 
Clinic will be a written letter and participants will be directed to NHSGGC Prof Guzik/Prof Delles led clinic. 

 
 
 
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4. Study Schedule and Trial procedures 
NB:  
 
Please refer to the InflammaTENSION Manual of Study Operations for an in-depth detail of the study 
procedures 
 
Please refer to Table 1: Study Schedule  
 
4.1 Recruitment 
Once identified and consented as described in section 3.4 the study visit activities can commence. 
 
4.3 Study Visit Information 
 
Location: All study visits will take place at Glasgow Clinical Research Facility 5th Floor, Neurosciences 
Building Queen Elizabeth University Hospital Campus 1345 Govan Road Glasgow G51 4TF 
 
Number of Study Visits:  All participants will attend a baseline study visit and visit 1 -either separately or 
combined depending on the participants wishes and availability of ABPM within past 3 months. 
 
An additional telephone contact and verification will be performed 3.5months +/- 2 weeks after final study visit 
to ensure secondary causes of hypertension would have not been identified in subsequent months.  
o 
In case of clinical need, and if subjects are agreeable, they will be referred to QEUH General 
Medicine/Hypertension Clinic,  led by NHSGGC Prof Guzik/Prof Delles for further diagnosis and 
treatment.. 
 
 

 
 
 
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4.4 Study Schedule and Trial Procedures 
Table 1: Schedule of InflammaTENSION Study procedures  
Study Procedure 
Baseline Visit 0 
at CRF 
Visit 1 at CRF 
Telephone 
visit/Letter Drop 
Timeframe 
V0 
V0+(0-72h) 
V1+12m±2w 
Demographic History 
X 
- 
x 
Medical History 
X 
- 
x 
Height and Weight 
X 
- 
x 
Urine Sample 
X 
- 
- 
Heart Rate 
X 
- 
- 
Office Blood Pressure measurement – 3 times 
following 15 minutes of rest 
X 
- 
- 
Venous Blood Sample (40ml) for Blood Tests and 
Immune signature/Biomarker analysis 
X 
- 
- 
Venous Blood Sample (10ml) for storage for 
subsequent genetic analysis 
X 
- 
- 
Ambulatory Blood Pressure Monitor Installation if 
no ABPM performed within past 3 months 
X 
- 
- 
MCQ 
- 
X 
- 
MoCA  
- 
X 
- 
DSS  
- 
X 
- 
IDQ  
- 
X 
- 
IPAQ  
- 
X 
- 
ABPM monitor will be returned 
- 
X 
- 
Carotid Intima-Media Thickness 
- 
X 
- 
Flow Mediated Dilation of Brachial Artery 
- 
X 
- 
Endo-PAT2000 
- 
X 
- 
Sphygmocor  study 
- 
X 
- 
 
Key 
- 
Not performed 
X  Performed 
h hours  
 
w – weeks 
 
m - months 
General Considerations 
In hypertensive subjects’ study visit(s) will be arranged as soon as possible after initial diagnosis of hypertension and 
before initiation of the treatment for hypertension. The study visit will not delay initiation of therapy in any way and will 
be fitted in between the hypertension work-up and subsequent clinic visit.  In subjects recruited from GHBPC (QEUH) 
this will be organized following initial diagnostic ABPM which is routinely performed prior to patient being seen by a 
consultant. In patients recruited from elsewhere – this will be arranged as soon as possible after identification and GP 
will be informed about ABPM which will be performed as part of the study by a letter from InflammaTENSION clinical 
team member. 
Secondary hypertension will be excluded as per routine clinical practice. We also planned a letter drop questionnaire 
or telephone visit/data review 3-4 months after initial visit in order to verify secondary/primary status of hypertension.  
While we have planned baseline visit and Visit 1 separately with ABPM being performed in between, subjects who do 
not require ABPM (it is available  within past 3 months) we will offer an option to combine these visits in one day for 
the patients.  
   
Baseline Visit (Visit 0)  
Meeting: The InflammaTENSION investigators will meet the participants at reception of the CRF. 

 
 
 
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Estimated Duration of Baseline Visit: Approximately 0.5 - 1 hours  
Recording of Study Information: The data from the study procedures will be recorded in the electronic case report 
form (e.g. CASTOR EDC). 
 
Study Procedures Performed at the Baseline Visit will include: 
 (Please refer to the InflammaTENSION Study Manual of Procedures for more details relating to the study 
procedures) 
• 
Demographic History 
• 
Medical History 
• 
Height and Weight 
• 
Urine Sample 
• 
Office Blood Pressure measurement – 3 times following 5 minutes of rest 
• 
Venous Blood Sample (40ml) for Blood Tests and Immune signature/Biomarker analysis 
• 
Venous Blood Sample (10ml) for storage for subsequent genetic analysis 
• 
Ambulatory Blood Pressure Monitor Installation if no ABPM performed within past 3 months 
• 
Subjects will be given an IDQ questionnaire (The Interheart Diet Questionnaire)  to be returned during visit 1 
 
All procedures will be performed in both Cases and Control groups including ABPM as it will ensure that hypertension 
is not missed by office blood pressure readings.  
 
Anonymisation 
 
Patient data will be pseudo-anonymised with a study number given to the patient. This study number will be 
used for blood tubes. The study specific number will be used for all storage of electronic and paper data 
relating to the; 
o 
Vascular function determinations 
o 
Immune signature determinations (cytokine/chemokine and cellular) 
o 
Cognitive function questionnaires 
o 
Will be blinded towards hypertension status and group allocation.  
 
Only the Chief Investigator, and designated and trained research fellow, who is a member of the direct care 
team, will have access to the participants' personal data during the study. These procedures will comply with 
the 1998 Data Protection Act. Biological samples collected from participants as part of this study will be 
transported, stored, accessed and processed in accordance with national legislation relating to the use and 
storage of human tissue for research purposes and such activities will meet the requirements as set out in the 
2004 Human Tissue Act and the 2006 Human Tissue (Scotland) Act. 
 
 
 
 
 
 
 
 

 
 
 
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Visit 1 (CRF) 
Study Procedures performed at Visit 1 at CRF (either in combination with baseline or up to 72h after baseline 
Visit) 
NB: There is no need for a study specific ABPM if a routine care ABPM has been performed within the past 3 months.  
This visit will take approximately 2-3.5 the following study procedures will be performed at the final visit.   
• 
Questionnaires 
 MCQ  
The Mild Cognitive Impairment Questionnaire 
 MoCA  
Montreal Cognitive Assessment  
 DSS   
Digital Symbol Substitution 
 IDQ   
The Interheart Diet Questionnaire 
 IPAQ  
The International Physical Activity Questionnaire  
• 
ABPM monitor will be returned 
• 
Carotid Intima-Media Thickness 
• 
Flow Mediated Dilation of Brachial Artery 
• 
Endo-PAT2000 
• 
Sphygmocor study 
Participants will be thanked for taking part in the InflammaTENSION study.  
 
Letter drop / Telephone contact (3.5 months +/- 14days) 
A follow - up letter will be sent by post or e-mail to all participants asking for filling in a questionnaire regarding the key 
changes in medical status since Visit 0. It will also announce possible telephone contact if no response is received to 
initial letter 
The telephone registration process will include: 
 
Obtaining information on participant health status changes; changes in demographics; changes in medical 
history and in particular verification if any cause for secondary hypertension has been identified. 

 
 
 
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4.5  
Study Outcome Measures  
4.5.1 
Primary Outcome Measure 
Cytokine and cellular immune signature of primary hypertension.  
Association between hypertensive status assessed by ABPM and immune signature analysed as a whole as well as 
individual pro- and anti- inflammatory cytokine levels and discreet immune cell populations. 
4.5.2 
Secondary Outcome Measure 
 
Association of selected cytokine/chemokine levels with vascular phenotypes 
 
endothelial function assessed by Endo-PAT2000, a non-invasive technique. 
 
Large vessel endothelial function assessed by brachial artery flow mediated dilatation, a non-invasive 
technique.   
 
Changes in cardiovascular parameters through non-invasive hemodynamic measurements   
 
Association of selected cytokine/chemokine levels with renal phenotypes 
 
GFR; renin levels; aldosterone levels 
 
Association of selected cytokine/.chemokine levels with cognitive dysfunction 
 
Results of MCQ, MoCA, DDS 
 
Association of selected cytokine/.chemokine levels with genetic variation assessed by GWAS 
 
4.6. 
Incidental findings 
Any incidental findings observed during the research procedures will be acted upon: this means that the PI takes 
responsibility to notify the patients GP and refer on for specialist follow up as appropriate and with the patient or 
participants permission.  
Patients who would benefit from hypertension/cardiovascular risk factor management will be referred to and provided 
with contact details for NHSGGC Prof Guzik/Prof Delles led clinic at the QEUH General Medicine/Hypertension Clinic 
for further diagnosis and treatment.  
 
 
 
 

 
 
 
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6. Statistics and Data Analysis Plan 
6.1 
Statistical Analysis Plan 
The InflammaTENSION study will have a comprehensive Statistical Analysis Plan, which will govern all statistical 
aspects of the study, and will be authored by the Study Statistician (Dr John McLure). To gain additional insight, 
variable selection analysis will be used to identify the best predictors of hypertension and its vascular outcomes 
(endothelial function/vascular compliance). To do this we will draw the expertise of local bioinformaticians (Dr John 
McClure) and of Professor Andrew Yates, a theoretical immunologist at University of Glasgow with experience in the 
modeling of cytokine networks and in machine learning approaches to TCR repertoire analysis.  We anticipate using 
exploratory unsupervised approaches such as Principle Component Analysis and clustering may be used on the 
cytokine profiles to identify signature patterns of cytokine expression that may allow a reduction of dimensionality. One 
can also associate each patient’s cytokine profile with a score - either one dimensional measure of disease severity or 
perhaps multi-factorial measures, combining severity with demographic data, for example, and use supervised 
learning approaches such as support vector machines or neural networks to generate classifiers or predictors of 
outcomes. 
6.2  
Sample Size  
The sample size will comprise of 120 participants per study arm (120 cases + 120 controls).  
Based on preliminary data: at least 116 subjects will allow us to detect an IL-6 difference of 25% at a two-sided alpha 
of 0.1% and power of 90% (multiple markers were tested, giving similar or smaller group; TNF- – 58 subjects). 87 
subjects/group for a 25% difference in CD8+CD25+ T cell (=0.1%, power - 90%). These analyses take into account 
multiple comparisons which are foreseen for immune signature determination.  
We believe that these projected effect sizes would potentially be clinically meaningful and credible.  
 
 

 
 
 
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7. Study Closure or Definition of End of Trial 
The study will end when: 
 
 
Final participants attend last study visit 
OR 
i. 
The planned sample size has been achieved; 
ii. 
There is insufficient funding to support further recruitment, and no reasonable prospect of additional support 
being obtained; 
iii. 
Recruitment is so poor that completion of the trial cannot reasonably be anticipated. 
 
 
 
 

 
 
 
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8. Data Handling 
8.1 Case Report Forms / Electronic Data Record 
An electronic case report form (e-CRF) will be used to collect study data.  The e-CRF will be developed by the study 
data centre at the CASTOR EDC (https://castoredc.com) and access to the e-CRF will be restricted, with only 
authorised site-specific personnel able to make entries or amendments to their Participants’ data. It is the 
investigator's responsibility to ensure completion and to review and approve all data captured in the e-CRF.  
 
All data handling procedures will be detailed in a Study Specific Data Management Plan.  Data will be validated at the 
point of entry into the e-CRF and at regular intervals during the study.  Data discrepancies will be flagged to the study 
site and any data changes will be recorded in order to maintain a complete audit trail (reason for change, date change 
made, who made change).  
8.2 Record Retention 
As discussed above in patient recruitment procedures, subjects will be initially identified by a member of the patient’s 
existing clinical care team who has access to patient records in relation to clinical service. They will inform the patient 
about the possibility of participating in a study.  
Patient data will be pseudo-anonymised with a study number given to the patient. This study number will be used for 
blood tubes. To enable evaluations and/or audits from regulatory authorities, the investigator agrees to keep records, 
including the identity of all participating subjects (sufficient information to link records), all original signed informed 
consent forms, in accordance with ICH GCP, local regulations, or as specified in the Clinical Study Agreement, 
whichever is longer. Data will be retained at the Data Centre for a minimum of 10 years. 
Only the Chief Investigator, who is a member of the direct care team, will have access to the participants' personal 
data during the study. These procedures will comply with the 1998 Data Protection Act. Biological samples collected 
from participants as part of this study will be transported, stored, accessed and processed in accordance with national 
legislation relating to the use and storage of human tissue for research purposes and such activities will meet the 
requirements as set out in the 2004 Human Tissue Act and the 2006 Human Tissue (Scotland) Act. 
Personal data will be stored on NHS password protected computers, which are secured as per local NHS protocols. 
No personal patient details will be on the University computers.  
Manual files with personal information will be kept in a secure location in the Clinical Research Facility, containing 
copies of the consent forms and a sample collection record. 
Only members of the study team will have access to any of the data generated. 
 
To enable evaluations and/or audits from regulatory authorities, the data will be retained at the Data Centre for 15 
years. The data records will include including the identity of all participating subjects, (to ensure the subjects 
information can be linked to records), all original signed informed consent forms, source documents, and detailed 
records of treatment disposition in accordance with ICH GCP, local regulations. 
 
 

 
 
 
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9. Protocol Amendments 
Any change in the study protocol will require an amendment.  Any proposed protocol amendments will be initiated by 
the principle investigators and any required amendment forms will be submitted to the regulatory authority, ethics 
committee and sponsor.  The principle investigators will liaise with study sponsor to determine whether an amendment 
is non-substantial or substantial.  All amended versions of the protocol will be signed by the principle investigator and 
Sponsor representative.  Before the amended protocol can be implemented favourable opinion/approval must be 
sought from the original reviewing Research Ethics Committee and Research and Development (R&D) office(s). 
 
 

 
 
 
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10. Ethical Considerations 
 
 
10.1 
Ethical conduct of the study 
The study will be carried out in accordance with the World Medical Association Declaration of Helsinki (1964) and its 
revisions (Tokyo [1975], Venice [1983], Hong Kong [1989], South Africa [1996] and Edinburgh [2000]). 
Favourable ethical opinion will be sought from an appropriate REC before Participants are entered into this clinical 
trial.  Participants will only be allowed to enter the study once either they have provided written informed consent  
The principle investigator will be responsible for updating the Ethics committee of any new information related to the 
study. 
10.2 
Informed consent 
Written consent will be obtained from each trial participant; each participant will receive a signed copy of the consent 
form. Participants unable to provide written informed consent will be excluded from the study.  
The Research Nurse or investigator will explain verbally and in writing the exact nature of the study in writing with the 
provision of Participant information sheet. This will include the known side-effects that may be experienced, and the 
risks of participating in this clinical trial.  Trial participants will be informed that they are free to withdraw their consent 
from the study or study treatment at any time. 
 
10.3. Assessment and management of risk 
The small amounts of venous blood which will be obtained are safe and do not pose any additional risk. All 
procedures for venepuncture will be fulfilled to ensure safety of participants and the procedure will be carried out by 
trained medical practitioner, member of InflammaTENSION team. 
  The study is classified as Type A = No higher than the risk of standard medical care 
 
10.4. Blinding 
Patient data will be pseudo-anonymised with a study number given to the patient. This study number will be used for 
blood tubes. These numbers will be used for blinding. All investigators performing clinical and laboratory assessment 
will be blinded towards hypertension status and group allocation of individual subjects.  
Only the Chief Investigator and research fellow trained who is a member of the direct care team will have access to 
the participants' personal data during the study. These procedures will comply with the 1998 Data Protection Act. 
Biological samples collected from participants as part of this study will be transported, stored, accessed and 
processed in accordance with national legislation relating to the use and storage of human tissue for research 
purposes and such activities will meet the requirements as set out in the 2004 Human Tissue Act and the 2006 
Human Tissue (Scotland) Act. 
 
 
 

 
 
 
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11. Insurance and Indemnity 
 
The InflammaTENSION study is sponsored by NHS GGC.  The sponsor will be liable for negligent harm..  NHS 
indemnity is provided under the Clinical Negligence and Other Risks Indemnity Scheme (CNORIS). Non-negligent 
harm from the protocol,  design of the study and which is therefore non-negligent, will be covered by the University of 
Glasgow. 
 
The NHS has a duty of care to Participants treated, whether or not the Participant is taking part in a research study, 
and the NHS remains liable for clinical negligence and other negligent harm to Participants under its duty of care. 
 
 

 
 
 
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12. Funding 
 
Funding for the InflammaTENSION study will be from the European Research Council and the BHF Centre of 
Excellence Award.  
 
Grant Funder: European Research Council and British Heart Foundations 
 
Grant award number: ERC Grant agreement in negotiations; BHF - RE/13/5/30177 
 
 

 
 
 
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13. Dissemination of Findings 
 
The research findings will be disseminated to healthcare professionals and public health specialists through 
newsletters; to members of the public by newspapers and other media as well as by information sessions; and to the 
wider scientific community through peer reviewed publications and presentations.  
No identifiable participant information will be detailed within the research findings 
 
 

 
 
 
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Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ and Harrison DG. Interleukin 17 promotes 
angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55:500-7. 
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Hoch NE, Guzik TJ, Chen W, Deans T, Maalouf SA, Gratze P, Weyand C and Harrison DG. Regulation of T-
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Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C and Harrison DG. 
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Lifton RP, Gharavi AG and Geller DS. Molecular mechanisms of human hypertension. Cell. 2001;104:545-56. 
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AD, Yao C, Ying SX, Courchesne P, Milani L, Raghavachari N, Wang R, Liu P, Reinmaa E, Dehghan A, 
Hofman A, Uitterlinden AG, Hernandez DG, Bandinelli S, Singleton A, Melzer D, Metspalu A, Carstensen M, 
Grallert H, Herder C, Meitinger T, Peters A, Roden M, Waldenberger M, Dorr M, Felix SB, Zeller T, 
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