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MIcrovascular dysfuNction In Moderate-severe Psoriasis (MINIMA)

Primary Purpose

Psoriasis

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Tildrakizumab

About this trial

This is an interventional treatment trial for Psoriasis

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

In order for an individual to participate, they must meet all of the inclusion and exclusion criteria as outlined below.

Inclusion Criteria include the following:

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.

Exclusion Criteria include the following:

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

Sites / Locations

Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Subjects treated with Tildrakizumab

Arm Description

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 along with echocardiography. The final PET scan and echocardiogram will occur at 6 months after the intervention.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Correlation between change in global CFR and psoriasis skin severity

Correlation between the change (from baseline) in global CFR and psoriasis skin severity scores (Body surface area [BSA], Physician's Global Assessment [PGA], Psoriasis Area and Severity Index [PASI]) at 24 weeks after initiation of Tildrakizumab

Change in peak-stress global myocardial blood flow

Change (from baseline) in peak-stress global myocardial blood flow (in mL/min/g) at 24 weeks after initiation of Tildrakizumab

Change in peak-stress global coronary vascular resistance

Change (from baseline) in peak-stress global coronary vascular resistance (in mm Hg/mL/min/g) at 24 weeks after initiation of Tildrakizumab

Change in LV peak global longitudinal strain and E'

Change (from baseline) in LV peak global longitudinal strain (GLS) and E' at 24 weeks after initiation of Tildrakizumab

Correlation of change in LV peak GLS and E' with global CFR

Correlation of the change (from baseline) in LV peak GLS and E' with the global CFR at 24 weeks after initiation of Tildrakizumab

Full Information

NCT ID

NCT04271540

First Posted

February 13, 2020

Last Updated

November 1, 2022

Sponsor

Marcelo F. Di Carli, MD, FACC

1. Study Identification

Unique Protocol Identification Number

NCT04271540

Brief Title

MIcrovascular dysfuNction In Moderate-severe Psoriasis

Acronym

MINIMA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 4, 2020 (Actual)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Marcelo F. Di Carli, MD, FACC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Psoriasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Subjects treated with Tildrakizumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tildrakizumab

Other Intervention Name(s)

Ilumya

Intervention Description

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 and echocardiogram 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 Other cardiac Imaging: An echocardiogram will be performed at baseline and at 6-months.

Primary Outcome Measure Information:

Title

Change in global coronary flow reserve (CFR) after 6 months of therapy with Tildrakizumab

Description

Change (from baseline) in global CFR, as measured by PET imaging at 24 weeks after initiation of Tildrakizumab therapy.

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Correlation between change in global CFR and psoriasis skin severity

Description

Time Frame

24 weeks

Title

Change in peak-stress global myocardial blood flow

Description

Change (from baseline) in peak-stress global myocardial blood flow (in mL/min/g) at 24 weeks after initiation of Tildrakizumab

Time Frame

24 weeks

Title

Change in peak-stress global coronary vascular resistance

Description

Change (from baseline) in peak-stress global coronary vascular resistance (in mm Hg/mL/min/g) at 24 weeks after initiation of Tildrakizumab

Time Frame

24 weeks

Title

Change in LV peak global longitudinal strain and E'

Description

Change (from baseline) in LV peak global longitudinal strain (GLS) and E' at 24 weeks after initiation of Tildrakizumab

Time Frame

24 weeks

Title

Correlation of change in LV peak GLS and E' with global CFR

Description

Correlation of the change (from baseline) in LV peak GLS and E' with the global CFR at 24 weeks after initiation of Tildrakizumab

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

In order for an individual to participate, they must meet all of the inclusion and exclusion criteria as outlined below. Inclusion Criteria include the following: 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. Exclusion Criteria include the following: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Marcelo F Di Carli, MD

Phone

617-732-3290

mdicarli@partners.org

First Name & Middle Initial & Last Name or Official Title & Degree

Leanne Barrett Goldstein

Phone

617-732-4719

lbarrett11@bwh.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marcelo F Di Carli, MD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marcelo Di Carli, MD

Phone

617-732-6290

mdicarli@partners.org

First Name & Middle Initial & Last Name & Degree

Leanne Barrett Goldstein

Phone

617-732-4719

lbarrett11@bwh.harvard.edu

First Name & Middle Initial & Last Name & Degree

Brittany Weber, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

MIcrovascular dysfuNction In Moderate-severe Psoriasis

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