Dapagliflozin and Endothelin Receptor Antagonism in Large Vessel Vasculitis (DERAIL-LVV)

Sponsor
University of Edinburgh
Study ID
NCT06887062
Phase
PHASE2
Status
Recruiting
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Conditions

  • Giant Cell Arteritis (GCA)
  • Large Vessel Vasculitis
  • Takayasu Arteritis

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Accepted

Interventions

  • Bosentan and dapagliflozin — DRUG
    Participants with LVV will receive Bosentan 62.5 mg twice daily and Dapagliflozin 10 mg once daily for 6 weeks, followed by Dapagliflozin 10 mg once daily for 4 weeks.

Study Details

Large vessel vasculitis (LVV) 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. Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor that has been shown to improve blood vessel function and stiffness in patients with diabetes. The investigators plan to assess blood vessel function in those with LVV and participants without LVV. Participants with LVV will be given Bosentan and Dapagliflozin for 6 weeks, followed by Dapagliflozin for 4 weeks, to evaluate their impact on blood vessel function.

Key Dates

Start date
Mar 21, 2025
Status verified
Jan 2026
Primary completion
Jul 1, 2027
Completion
Jul 1, 2027

Study Design

Enrollment
60 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: 30 participants with large vessel vasculitis in disease remission
    * Participants will undergo a forearm blood flow study where forearm vasodilatation will be assessed in response to acetylcholine (7.5, 15 and 30ug/min) and sodium nitroprusside (1, 2 and 4ug/min). * Participants will also receive bradykinin (100, 300 and 1000pmol/min) in order to assess tPA release to measure fibrinolytic capacity. * Participants will also have 24-hour blood pressure measured, as well as measurements of arterial stiffness, choroidal volume and balance of peripheral inflammatory and anti-inflammatory cells. * After these baseline measurements have been obtained, the subject will receive 6 week of Bosentan. The participant will undergo the same investigations to compare if measurements differ after treatment.
  • No Intervention: 30 age-, sex- and cardiovascular disease risk-matched control participants
    * Participants will undergo a forearm blood flow study where forearm vasodilatation will be assessed in response to acetylcholine (7.5, 15 and 30ug/min) and sodium nitroprusside (1, 2 and 4ug/min). * Participants will also receive bradykinin (100, 300 and 1000pmol/min) in order to assess tPA release to measure fibrinolytic capacity. * Participants will also have 24-hour blood pressure measured, as well as measurements of arterial stiffness, choroidal volume and balance of peripheral inflammatory and anti-inflammatory cells. * These measurements will be compared to the large vessel vasculitis group to assess if there are differences in these measurements.

Primary Outcome Measure

Change from baseline to week 6 in forearm blood flow [ Time Frame: Before and after 6 weeks of treatment ]

Central Contacts

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