dual endothelin receptor antagonism in large vessel vasculitis (derail-lvv)

Conditions: Large Vessel Vasculitis; Giant Cell Arteritis (GCA); Takayasu Arteritis

Summary: large vessel vasculitis is a disease that causes damage to blood vessels. this damage to blood vessels can increase the risk of patients with lvv developing cardiovascular disease, including heart attacks and strokes. a chemical produced in the body called endothelin may contribute to this increase in cardiovascular disease risk by causing the vessels to stiffen and blood pressure to increase. it has previously been shown that by blocking the effects of endothelin, vessel stiffness and blood pressure improve. bosentan is a tablet that blocks the effects of endothelin. the investigators plan to assess blood vessel function in those with lvv and participants without lvv. participants with lvv will then be given bosentan for 6 weeks to evaluate its impact on blood vessel function.

large vessel vasculitis (lvv) is an autoimmune disease characterised by inflammatory damage to the blood vessels. although symptoms initially are non-specific, complications such as vessel stenosis can lead to heart failure and stroke. while current immunosuppressive treatments have improved short-term outcomes, they have not led to improvements in long-term outcomes. patients with lvv remain at an increased risk of developing cardiovascular disease, the underlying mechanisms of which are not yet fully understood. the inflammatory damage to blood vessels in lvv can result in endothelial dysfunction. endothelin-1 (et-1) is a potent vasoconstrictor produced by the endothelium. in endothelial dysfunction, excess et-1 production causes raised blood pressure, increased arterial stiffness and reduced fibrinolytic capacity. previous research has demonstrated that short-term blockade of endothelin receptors improves arterial stiffness and fibrinolytic capacity. the investigators will conduct a cross-sectional, case-control study comparing endothelial function in patients with lvv with sex-, age-, and cardiovascular disease risk factor-matched control participants. this will be followed by an open-label study involving 6 weeks of treatment with bosentan (a dual endothelin receptor antagonist) within the lvv group to assess whether this drug can improve endothelial function. assessment of endothelial function will be carried out by forearm plethysmography which is the gold standard.

Eligibility criteria:
inclusion criteria: * a diagnosis of large vessel vasculitis that has been in remission for ≥ 6 months. exclusion criteria: * age \<18 years * active lvv * any organ transplant recipients * a requirement for any medications that are contra-indicated whilst taking bosentan * congestive cardiac failure * patients not medically fit to attend study visits * patients without mental capacity or willingness to provide informed consent * history of multiple and/or severe (clinical judgement as determined by the investigator) allergic reactions to drugs, including the study drug, or food * patients who are pregnant or breast feeding, or those who plan to become pregnant during the study * participation in another clinical trial for 28 days before or 90 days after the study period

Keywords: large vessel vasculitis takayasu arteritis giant cell arteritis endothelin bosentan inflammation endothelial dysfunction dual enodthelin receptor antagonism