NCT04271540

MIcrovascular dysfuNction In Moderate-severe Psoriasis

Effects of Tildrakizumab on Coronary Microvascular Function in Moderate-Severe Psoriasis

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Marcelo F. Di Carli, MD, FACC · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

Psoriasis, a common chronic inflammatory skin disease affecting approximately 2% of the population, is associated with increased cardiovascular (CV) risk. Despite the implication of inflammation in this excess risk, it remains unclear whether reducing inflammation reduces the risk of cardiac events. This study proposes to test whether Tildrakizumab, an FDA approved therapy for psoriasis that blocks IL-23 and the Th17 pathway of inflammation, improves coronary vascular function and coronary flow reserve, as measured by noninvasive imaging with cardiac positron emission tomography. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular deformation and function and, ultimately, symptoms and prognosis. This research may offer novel insights into the contributors of CV risk in psoriasis and provide data to support the development of strategies to prevent cardiovascular events in psoriatic disease.

Detailed description

The primary objective of this study is to investigate the impact of Tildrakizumab therapy on coronary vasoreactivity and myocardial mechanics, as indicators of subclinical cardiovascular disease in patients with psoriatic disease and intermediate-high CV risk. Impaired coronary flow reserve (CFR) is a measure of coronary vasoreactivity and a manifestation of myocardial ischemia which may precede clinical CV events (and visible changes in plaque morphology) in high-risk patients with psoriatic disease. From previous studies, it is known that traditional risk factors underestimate cardiovascular risk in psoriatic disease. Tildrakizumab, a p19 inhibitor which blocks IL-23 and Th17 mediated inflammation, is an FDA approved therapy for moderate-severe psoriasis and has been shown to reduce inflammation. Furthermore, IL-17 is associated with endothelial dysfunction and atherosclerosis. The central hypothesis is that reducing systemic inflammation using tildrakizumab will quantitatively improve myocardial blood flow and CFR as measured by PET over 6 months; and this improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular function and, ultimately, symptoms and prognosis. This is a single-arm open-label mechanistic clinical study in adult subjects with moderate-severe psoriasis and increased cardiovascular risk. We plan to enroll approximately 35 patients to receive Tildrakizumab over 6 months. The study will consist of 4-5 visits including a virtual or in person screening visit, a baseline visit in which baseline imaging tests will be conducted and study drug will be dispensed, two in person visits for which study drug will be given and monitoring of AE events and compliance, and a final visit in visit in which imaging tests will be repeated

Conditions

• Psoriasis
• Cardiovascular Disease

Interventions

Type	Name	Description
DRUG	Tildrakizumab	Tildrakizumab, a p19 inhibitor which blocks IL-23 and Th17 mediated inflammation, will be given for 6 months. As below, a baseline cardiac PET scan will be performed prior to initiation and after 6 months of treatment. Radiation: A cardiac PET scan will be performed at baseline and at 6 months

Timeline

• Start date: 2020-04-04
• Primary completion: 2024-07-03
• Completion: 2024-07-17
• First posted: 2020-02-17
• Last updated: 2025-11-25
• Results posted: 2025-11-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study