A mechanistic study using GTN to investigate digital ulcer physiology

  • Research type

    Research Study

  • Full title

    A mechanistic study of topical glyceryl trinitrate to understand the pathophysiology of digital ulcers in systemic sclerosis

  • IRAS ID

    135068

  • Contact name

    Michael Hughes

  • Contact email

    michael.hughes-6@postgrad.manchester.ac.uk

  • Sponsor organisation

    The University of Manchester

  • Research summary

    Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune connective tissue disease that involves changes in the skin, blood vessels and most of the internal organs.

    Digital ulcers (finger and toe) which occur in around 50% of patients with SSc at some point in their disease course, are often very painful and can become infected. They can be very disabling in affecting patient’s hand function and quality of life. Current treatments aim to increase perfusion (blood flow) to the ulcer through ’vasodilation’ (that is, by the dilation of the blood vessels), however such treatments are often poorly tolerated (and not uncommonly discontinued) due to intolerable systemic side effects.

    Relatively little is know about the pathophysiology of digital ulcers in patients with SSc. It is currently believed that fingertip digital ulcers are ischaemia (lack of blood flow)-driven while those over extensor surfaces may be more related to mechanical abnormalities and micro-trauma. However, recent work has suggested that extensor surface ulcers may also have an ischaemic component. A greater understanding of the pathophysiology of digital ulcers will help to direct future research into well tolerated, effective local treatments (including those that increase blood flow to the ulcer).

    We plan to investigate the response of the blood vessels to topical glyceryl trinitrate (GTN): a well studied vasodilatory drug, applied at the base and the perimeter of SSc digital ulcers (fingertip and extensor aspect), and whether the response of blood vessels at these locations differs to those in normal healthy skin.

  • REC name

    North West - Preston Research Ethics Committee

  • REC reference

    13/NW/0684

  • Date of REC Opinion

    9 Oct 2013

  • REC opinion

    Further Information Favourable Opinion