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

NCT06887062 | Recruiting Phase 2

• 1 other identifier: AC24184
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Large vessel vasculitis; Takayasu arteritis; Giant cell arteritis; Endothelin; Bosentan; Inflammation; Endothelial dysfunction; Dual enodthelin receptor antagonism; dapagliflozin; SGLT2 inhibitor

Outcome Measures

Primary Outcomes (1)

• Change from baseline to week 6 in forearm blood flow

  Change from baseline to week 6 in acetylcholine-mediated forearm blood flow vasodilation

  Before and after 6 weeks of treatment

Secondary Outcomes (5)

• Change from Baseline to week 6 in fibrinolytic capacity

  Before and after 6 weeks of treatment

• Change from Baseline to week 6 in 24h blood pressure

  Before and after 6 weeks of treatment

• Change from baseline to week 6 in arterial stiffness

  Before and after 6 weeks of treatment

• Change from baseline to week 6 assessment of eye microvasculature using retinal OCT

  Before and after 6 weeks of treatment

• Change from baseline to week 6 peripheral blood cells (balance of inflammatory and anti-inflammatory cells) analysed using flow cytometry

  Before and after 6 weeks of treatment

Study Arms (2)

30 participants with large vessel vasculitis in disease remission

EXPERIMENTAL

* 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.

Drug: Bosentan and dapagliflozin

30 age-, sex- and cardiovascular disease risk-matched control participants

NO INTERVENTION

* 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.

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.

30 participants with large vessel vasculitis in disease remission

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of large vessel vasculitis that has been in remission for ≥ 6 months.

You may not qualify if:

• Age \<18 years
• Active LVV
• Any organ transplant recipients
• A requirement for any medications that are contra-indicated whilst taking Bosentan or dapagliflozin
• 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

Sponsors & Collaborators

• University of Edinburgh: lead

Study Sites (1)

University of Edinburgh

Edinburgh, EH16 4TJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Giant Cell Arteritis; Takayasu Arteritis; Inflammation

Interventions

Bosentan; dapagliflozin

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Aortic Arch Syndromes; Aortic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Alex Armstrong

CONTACT

+447445695898; a.armstrong-9@sms.ed.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will incorporate both a prospective, case-control study and a nested prospective, open blinded study. Case-control study: this will be cross-sectional and assess endothelial function, arterial stiffness and 24-hour blood pressure in 30 patients with LVV in disease remission and 30 age-, sex- and cardiovascular risk factor-matched control subjects. Open-blinded study: This will be a 10-week open-blinded study in the same 30 subjects with LVV from the case-control study. All 30 participants will receive 6 weeks of bosentan and dapagliflozin, followed by 4 weeks of dapagliflozin. Outcomes will be measured at baseline, week 3, week 6 and week 10.

Study Record Dates

• First Submitted: March 13, 2025
• First Posted: March 20, 2025
• Study Start: March 21, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

GB (1)