TSPO, endothelial function and total pulmonary resistance

• Research type

  Research Study

• Full title

  Investigating the relationship between endothelial cell activation and total pulmonary resistance in pulmonary artery hypertension (PAH)

• IRAS ID

  316863

• Contact name

  Martin Wilkins

• Contact email

  m.wilkins@imperial.ac.uk

• Clinicaltrials.gov Identifier

  NCT06035861

• Duration of Study in the UK

  1 years, 4 months, 1 days

• Research summary

  Background
  Pulmonary arterial hypertension (PAH) is a rare condition where blood flow in the lung is reduced (despite no disease in the lung itself). This leads to heart failure and premature death. In around half of patients there is no identifiable underlying cause. Examination of the lung after death shows that the arteries have altered their structure considerably and the cells lining the blood vessels have proliferated. There are several treatments available, but whilst these treatments improve symptoms, unfortunately they have little impact on the underlying disease process, and do not reverse or even slow down the course of the condition.
  Some researchers believe that “endothelial cells” (the cells which make up the inner lining of the blood vessel) are partly responsible for the disease and that they drive the disease by becoming activated. Therefore, if you could prevent endothelial cells activating, this might be a way of slowing the disease.

  We have shown that a drug (XBD173) which targets a protein called the 18kDa Translocator Protein (TSPO), reduces endothelial activation. In this study, we would like to use this drug to modulate endothelial activation, in order to determine whether endothelial dysfunction drives total pulmonary resistance in patients with PAH.

  Study design
  We will give people with PAH XBD173 for 8 weeks, and measure whether the drug affects blood tests which reflect endothelial cell activation. The participants we will include already have implantable devices (placed on advice of their clinician, independent of this study) which measure physiological markers in the lung and therefore allow us to measure the effect of the drug on lung vascular resistance.

  Who is funding the research?
  Imperial College London

  Where is will be recruiting?
  University of Sheffield
  

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  22/LO/0657

• Date of REC Opinion

  5 Dec 2022

• REC opinion

  Further Information Favourable Opinion