PRIZE trial sub-study investigating SNPs in microvascular angina
Research type
Research Study
Full title
Mechanistic study of the effect of ET-1 SNPs in Coronary Microvascular Disease
IRAS ID
283303
Contact name
Stephen Hoole
Contact email
Sponsor organisation
Royal Papworth Hospital
Eudract number
2020-003964-18
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
NCT04508998, NCT
Duration of Study in the UK
1 years, 11 months, 29 days
Research 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.REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
20/EM/0279
Date of REC Opinion
7 Dec 2020
REC opinion
Further Information Favourable Opinion