PRIZE ET Sub-Study
Mechanistic Study of the Effect of ET-1 SNPs in Coronary Microvascular Disease
1 other identifier
interventional
26
1 country
1
Brief Summary
Microvascular angina (MVA) is caused by abnormalities of the small blood vessels in the heart. Endothelin-1 (ET-1) is a chemical messenger that circulates and accumulates in the blood vessel walls, causing them to narrow or go into spasm and thicken over a long period, especially as levels of ET-1 increase. As a result, patients experience pain, psychological distress and limitation of their daily activities. Cambridge is a participating recruitment site for a large randomised, double blinded, placebo controlled crossover trial (the PRIZE study: NCT04097314) investigating Zibotentan as a new drug treatment for patients with MVA using a 'precision medicine' approach. Zibotentan is a drug originally developed by Astra Zeneca for prostate cancer but prior research has shown that it acts to relax the small blood vessels of patients with MVA, highlighting its potential as a novel therapy for this patient group. The PRIZE study population will be enriched for 'responders' to the drug by screening patients with MVA for a gene mutation known to increase levels of circulating endothelin. The trial aims to initially invite approximately 356 participants for genetic testing but only 100 participants will go forward into the main study, with approximately 2/3rd being screen failures. In our sub-study, we will invite patients with MVA who are screen failures at our site for further blood tests looking for other genetic variants in the ET-1 signalling pathway and examine how this correlates with the severity of microvascular angina quantified by cardiac MRI and clinical assessments. Data from this sub-study would provide a bio-resource for further analysis of the main PRIZE trial to identify other patients that would benefit from Zibotentan.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started May 2021
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 21, 2020
CompletedFirst Posted
Study publicly available on registry
August 11, 2020
CompletedStudy Start
First participant enrolled
May 14, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 13, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 13, 2022
CompletedApril 4, 2023
April 1, 2023
1.2 years
June 21, 2020
April 1, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Correlation of ET-A SNPs with ET-A expression in blood by qPCR, levels of endothelin related plasma peptides and clinical data (exercise duration and microvascular disease measured by quantitative perfusion on Cardiac MRI)
Measurement of molecules associated with the endothelin signalling pathway in patients with different SNPs for the ET-A receptor will be compared with phenotypic characteristics of the patients, specifically exercise tolerance and by retrospective analysis of the patient's cardiac MRI using quantitative measures of myocardial blood flow.
correlation will be assessed at baseline at the start of the trial (time point 0)
Study Arms (1)
Patients with microvascular angina
EXPERIMENTALPatients with clinical features of microvascular angina screened for the main PRIZE trial however not possessing the PHACTR1 GG minor allele single nucleotide polymorphism
Interventions
Blood tests for alternative SNPs altering levels of ET-A receptor expression; blood will be further analysed for endothelin receptor mRNA and other plasma peptides important in the endothelin signalling pathway
Treadmill exercise test using the Bruce protocol
Eligibility Criteria
You may qualify if:
- Age \>18 years.
- Probable or definite Microvascular Angina as defined in COVADIS criteria:
- Clinical symptoms of angina
- No obstructive coronary artery disease
- Objective evidence of myocardial ischemia
- Evidence of impaired coronary microvascular function (Optional)
- Able to comply with study procedures.
- Screen failure for the main PRIZE study
- Written informed consent.
You may not qualify if:
- \. Lack of informed consent for the PRIZE ET Sub-study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Royal Papworth Hospital NHS Foundation Trust
Cambridge, CB2 0AY, United Kingdom
Related Publications (1)
Abraham GR, Morrow AJ, Oliveira J, Weir-McCall JR, Davenport EE, Berry C, Davenport AP, Hoole SP. Mechanistic study of the effect of Endothelin SNPs in microvascular angina - Protocol of the PRIZE Endothelin Sub-Study. Int J Cardiol Heart Vasc. 2022 Feb 25;39:100980. doi: 10.1016/j.ijcha.2022.100980. eCollection 2022 Apr.
PMID: 35242999BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen Hoole
Royal Papworth NHS Foundation Trust
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER GOV
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 21, 2020
First Posted
August 11, 2020
Study Start
May 14, 2021
Primary Completion
August 13, 2022
Study Completion
August 13, 2022
Last Updated
April 4, 2023
Record last verified: 2023-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF, CSR
- Time Frame
- A combined analysis with other leftover patient samples from other PRIZE trial participating sites is in progress. It is anticipated the clinical study report will be available in February 2024
- Access Criteria
- Individual participant data will not be shared routinely in this or any related research.
Data will be entered on electronic clinical record forms inputed on the Open Clinica eCRF platform with password protected access for researchers and for quality assurance personnel only.