MIcrovascular dysfuNction In Moderate-severe Psoriasis

NCT ID: NCT04271540

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-04
• Study Completion Date: 2024-07-17

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subjects treated with Tildrakizumab

Informed consent will be obtained from study participants willing to participate in MiNIMA. Study participants will then undergo the baseline rest/stress cardiac PET scan. The final PET scan will occur at 6 months after the intervention.

Group Type: EXPERIMENTAL

Tildrakizumab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Ilumya

Eligibility Criteria

Inclusion Criteria

1. Moderate-to-severe psoriasis

2. Ages 18-90

3. Body surface area (BSA) involvement ≥ 3% OR 5-point Physician Global Assessment (PGA) Score ≥ 3 OR Psoriasis Area and Severity Index (PASI) score ≥ 12

4. Patients who have failed biologic therapy, topical steroids, phototherapy, or other systemic therapies will be required to have a wash-out period, which will be calculated accordingly to the specific drug (Appendix 1)

5. Evidence of at least one cardiovascular risk factor which includes hsCRP ≥ 2 mg/L, DM, obesity (BMI>25), hyperlipidemia, hypertension, family history of early coronary artery disease, or evidence of metabolic syndrome

---Metabolic syndrome defined as at least three of the following: glucose>100mg/dl or taking hypoglycemic agent, HDL<40mg/dl (men) or 50 mg/dl (women), triglycerides ≥150mg/dl, waist circumference >40 in mean or >35 in women, or blood pressure ≥130/85 or taking anti-hypertensive.

6. If the patient is on a statin therapy, they must be on a stable dose for at least 6 months prior to enrollment.

Exclusion Criteria

1. Documented history of other systemic inflammatory diseases, including SLE and RA, which in the opinion of the investigator would be inappropriate for enrollment.

2. Prior history of untreated chronic infection (tuberculosis), severe fungal infection, or known HIV positive, chronic hepatitis B or C infection), prior history of active solid malignancy, myeloproliferative or lymphoproliferative disease within 5 years, excluding treated non-melanoma skin cancer

3. Renal insufficiency (CrCl <40 ml/min)

4. NYHA class IV heart failure

5. Patients requiring chronic treatment with oral prednisone >10mg/day, methotrexate, or other immunosuppressive agents.

6. Pregnancy and Breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marcelo F. Di Carli, MD, FACC

OTHER

Sponsor Role: lead

Responsible Party

Marcelo F. Di Carli, MD, FACC

Chief, Nuclear Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marcelo F Di Carli, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020P000200

Identifier Type: -

Identifier Source: org_study_id