Investigating the role of salt inducible kinases in atherosclerosis

ISRCTN	ISRCTN14632677
DOI	https://doi.org/10.1186/ISRCTN14632677
Secondary identifying numbers	2015CV11

Submission date: 10/06/2016
Registration date: 28/06/2016
Last edited: 09/11/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Cardiovascular disease (CVD) is a medical term used to describe a disease of the heart or blood vessels. This includes heart attacks (myocardial infarction, or MI) and stroke.In the early stages, however, it causes changes in the function of the blood vessels, particularly the arteries (vessels that transport blood being pumped from the heart to other areas of the body) . Some of these changes in function is due to inflammation (swelling) and, in theory, reducing this inflammation could reduce the risk of an MI or stroke. Animal studies have shown that certain substances (called SIKs) promote inflammation in the arteries. This study is investigating whether this is the same for humans by doing tests in both healthy volunteers and people that have cardiovascular disease (for example, have had a heart attack or have narrowing of the leg arteries). SIK levels will also be compared with the results from different measures of artery function. If SIK levels are found to be high in cases of poor artery function then this might be a potential new treatment target to prevent cardiovascular disease.

Who can participate?
Three different groups of people are participating in this study. People with peripheral vascular disease and about to have an amputation (group 1), people who have had a heart attack (group 2) and healthy volunteers (group 3). All participants are adults aged between 18-70.

What does the study involve?
Participants in group 1 are asked to give blood for analysis and their amputated tissue is also analysed. Participants in group 2 are also asked to give blood samples and undergo tests to see how stiff their arteries are (arterial stiffness measurements) and how well blood vessels relax after being dilated (widened with increased blood flow). Participants in group 3 are also asked to give blood samples, flow-mediated dilatation (blood vessels widened with increased blood flow) and pulse-wave analysis (arterial stiffness analysis). All participants are followed up for signs of inflammation, their blood vessel function and SIK levels.

What are the possible benefits and risks of participating?
The researchers do not expect there to be any direct risks or benefits to the patient in taking part in the study. Routine clinical care will not be affected regardless of participation in the study. For volunteers, there is the small discomfort of having blood samples taken, however steps will be made to make this as easy as possible.

Where is the study run from?
Ninewells Hospital, Dundee (UK)

When is the study starting and how long is it expected to run for?
February 2016 to November 2017

Who is funding the study?
Tenovus (UK)

Who is the main contact?
Dr Faisel Khan
f.khan@dundee.ac.uk

Contact information

Dr Faisel Khan
Scientific

Division of Cardiovascular and Diabetes Medicine
Mailbox 1 Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom

ORCID ID	0000-0002-9889-0229
Phone	+44 (0)1382 383531
Email	f.khan@dundee.ac.uk

Study information

Study design	Observational cross-sectional study
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	Hospital
Study type	Diagnostic
Scientific title	Investigating the role of salt inducible kinases in atherosclerosis: a observational cross-sectional study
Study objectives	The key hypothesis is that the SIK-CRTC3 signalling axis will play an important role in development of atherosclerosis. The researchers hypothesise that mechanisms to activate the cAMP response element binding protein (CREB) should protect against cardiovascular disease (CVD), and that inhibition of salt inducible kinase 2 (SIK2) will have beneficial effects on the cardiovascular (CV) system and thus offer a new target for therapy.
Ethics approval(s)	East of Scotland Research Ethics Committee 2.
Health condition(s) or problem(s) studied	STEMI, peripheral arterial disease
Intervention	Three groups will be evaluated in this study: Group 1. 10 patients with peripheral vascular disease (PVD) undergoing elective amputation. These patients will undergo blood sampling and amputated tissue analysis. Group 2. 40 patients with acute myocardial infarction with ST elevation (STEMI) and requiring primary percutaneous coronary intervention (PPCI). These patients will undergo blood samples, flow mediated dilatation (FMD) and arterial stiffness measurements. Group 3. 40 healthy subjects, matched to the STEMI group for age and gender. They will undergo blood samples, flow-mediated dilatation and pulse wave analysis.
Intervention type	Other
Primary outcome measure	Serum levels of inflammatory cytokines taken at the time of operation in PVD group, 48-72 hours after PCI in STEMI group and at the time of assessment in healthy volunteers.
Secondary outcome measures	1. Tissue SIK levels in PVD patients at the time of surgery 2. Arterial stiffness and flow mediated dilatation in STEMI patients at 48-72 hours and in healthy volunteers at the time of assessment
Overall study start date	01/02/2016
Completion date	03/11/2017

Eligibility

Participant type(s)	Mixed
Age group	Adult
Lower age limit	18 Years
Upper age limit	70 Years
Sex	Both
Target number of participants	90
Total final enrolment	70
Key inclusion criteria	PVD: 1. Age between 18-70 years 2. Admitted for elective amputation for PVD 3. Able to give written informed consent STEMI: 4. Age between 18-70 years 5. Admitted to CCU for STEMI and undergone PPCI 6. Able to give written informed consent Healthy volunteers: 7. Age between 18-70 years 8. No current or previous significant medical illness 9. Able to give written informed consent
Key exclusion criteria	Healthy volunteers: 1. Positive medical history of: 1.1. Vascular diseases such as peripheral arterial disease, stroke, IHD... etc 1.2. Haematological conditions such as hypercoagulability, deep venous thrombosis... etc 1.3. Hypertension 2. Alcohol excess 3. Unable to give written informed consent STEMI/PVD: Unable to give written informed consent
Date of first enrolment	01/08/2016
Date of final enrolment	16/11/2017

Locations

Countries of recruitment

Scotland
United Kingdom

Study participating centre

Ninewells Hospital

Dundee
DD1 9SY
United Kingdom

Sponsor information

NHS Tayside/University of Dundee
University/education

c/o Mrs Natalie Smith
Tayside Medical Sciences Centre
3 George Pirie Way
Ninewells Hospital
Dundee
DD1 9SY
Scotland
United Kingdom

"ROR"	https://ror.org/000ywep40

Funders

Funder type

Charity

Tenovus
Private sector organisation / Other non-profit organizations

Alternative name(s): Tenovus Cancer Care
Location: United Kingdom

Results and Publications

Intention to publish date	03/11/2018
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	We intend to publish the results at the end of the study in peer-reviewed journals although details are not confirmed as yet.
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results		03/05/2019	17/05/2019	No	No

Additional files

ISRCTN14632677_BasicResults_03May19.pdf: uploaded 17/05/2019

Editorial Notes

09/11/2020: Internal review.
17/05/2019: The following changes were made to the trial record:
1. The basic results of this trial have been uploaded as an additional file.
2. The total final enrolment was added.
3. The recruitment end date was changed from 01/08/2017 to 16/11/2017.
26/11/2018: Internal review.