Study of ET-1 SNP Effects on ET-1 Antagonism in Coronary Microvascular Disease
Status:
Not yet recruiting
Trial end date:
2023-02-01
Target enrollment:
Participant gender:
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 in the longer term,
especially as levels of ET-1 increase. As a result, patients experience pain, psychological
distress and limitation of their daily activities.
Originally developed by AstraZeneca for cancer treatment, prior research has confirmed that
Zibotentan relaxes the small blood vessels of patients with MVA which lends support to the
idea that Zibotentan may bring some benefits to patients with MVA. We are interested in
re-purposing Zibotentan as a new treatment for patients with MVA and Cambridge is a
participating recruitment site for a large trial (the PRIZE study) to look at this. The study
will enrich for 'responders' by screening patients with MVA for a gene mutation that
increases levels of circulating endothelin. The trial aims to initially invite approx. 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 broaden inclusion by inviting patients with MVA who are screen
failures at our site into a sub-study assessing the effect of Zibotentan in patients with
different genetic variants in the ET-1 pathway and degrees of microvascular angina quantified
by cardiac MRI to assess the therapeutic potential of Zibotentan in other patient groups.
Data from this sub-study could justify further analysis of the main study as well as being a
genetic repository and bio-resource for future research.