MIcrovascular dysfuNction In Moderate-severe Psoriasis

NCT04271540 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2020P000200
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Psoriasis; Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• Change in Global Coronary Flow Reserve (CFR) After 6 Months of Therapy With Tildrakizumab

  Change (from baseline) in global CFR, as measured by PET imaging at 24 weeks after initiation of Tildrakizumab therapy. Coronary flow reserve (CFR), the ratio of peak vasodilator stress to rest myocardial blood flow (MBF), represents the maximal ability to augment coronary flow and myocardial perfusion. Absolute MBF was computed from the rest and stress myocardial perfusion PET images using commercially available software (Corridor4DM; Ann Arbor, Michigan) and a two-compartment tracer kinetic model. Impaired MBFR is defined as a ratio of \<2.0, which is associated with increased cardiovascular risk.

  24 weeks

Secondary Outcomes (3)

• Correlation Between Change in Global CFR and Psoriasis Skin Severity

  24 weeks

• Change in Peak-stress Global Myocardial Blood Flow

  24 weeks

• Change in Peak-stress Global Coronary Vascular Resistance

  24 weeks

Study Arms (1)

Subjects treated with Tildrakizumab

EXPERIMENTAL

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.

Drug: Tildrakizumab

Interventions

Tildrakizumab 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

Also known as: Ilumya

Subjects treated with Tildrakizumab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Moderate-to-severe psoriasis
• Ages 18-90
• Body surface area (BSA) involvement ≥ 3% OR 5-point Physician Global Assessment (PGA) Score ≥ 3 OR Psoriasis Area and Severity Index (PASI) score ≥ 12
• 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)
• 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.
• If the patient is on a statin therapy, they must be on a stable dose for at least 6 months prior to enrollment.
• Documented history of other systemic inflammatory diseases, including SLE and RA, which in the opinion of the investigator would be inappropriate for enrollment.
• 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
• Renal insufficiency (CrCl \<40 ml/min)
• NYHA class IV heart failure
• Patients requiring chronic treatment with oral prednisone \>10mg/day, methotrexate, or other immunosuppressive agents.
• Pregnancy and Breastfeeding

Sponsors & Collaborators

• Marcelo F. Di Carli, MD, FACC: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Psoriasis; Cardiovascular Diseases

Interventions

tildrakizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

This study is a pilot, mechanistic study, and should be viewed in light of this. Larger studies are warranted with longer follow-up to address whether myocardial blood flow improves over a longer duration. Conversely, whether myocardial blood flow worsens in the absence of IL-23 blockade could only be examined in a patient population of moderate-severity who are not treated.

Results Point of Contact

• Title: Brittany Weber, MD, PhD
• Organization: Brigham and Women's Hospital

bweber@bwh.harvard.edu

6177326291

Study Officials

• Marcelo F Di Carli, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Nuclear Medicine

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: April 4, 2020
• Primary Completion: July 3, 2024
• Study Completion: July 17, 2024
• Last Updated: November 25, 2025
• Results First Posted: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)