Advanced Cardiovascular Imaging of the Systemic Effects of Inflammasome Activation

Sponsor

University of Virginia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05880355

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Subjects with urgently reperfused type I myocardial infarction (MI) will be recruited and randomized to receive either placebo or the oral inflammasome (NLRP3) inhibitor dapansutrile. The primarily outcome measure will be carotid plaque volume change over 6 months; secondary outcome measures will be plaque inflammatory activity and coronary microvascular function.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Drug: Dapansutrile Other: Placebo	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, single blind study.Randomized, single blind study.

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Advanced Cardiovascular Imaging of the Systemic Effects of Inflammasome Activation

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Dec 31, 2027

Anticipated Study Completion Date :

Oct 30, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dapansutrile Subjects randomized to receive oral dapnsutrile	Drug: Dapansutrile Oral inhibitor of NLRP3
Placebo Comparator: Control Subjects randomized to receive oral placebo	Other: Placebo Non-active placebo

Arm

Intervention/Treatment

Experimental: Dapansutrile

Subjects randomized to receive oral dapnsutrile

Drug: Dapansutrile

Oral inhibitor of NLRP3

Placebo Comparator: Control

Subjects randomized to receive oral placebo

Other: Placebo

Non-active placebo

Outcome Measures

Primary Outcome Measures

Remote plaque volume [6 months]
Carotid artery plaque volume change by ultrasound measured by 3D ultrasound. Outcome units will be cm3 averaged for bilateral carotid arteries.

Secondary Outcome Measures

Plaque inflammation [3 months]
Carotid artery plaque inflammatory activity by PET-CT. Units will be SVU averaged bilaterally for a region-of-interest over the carotid bifurcation.
Coronary microvascular function [3 months]
Coronary microvascular reactivity by myocardial contrast echo (MCE) quantitative perfusion imaging. The primary endpoint unit will be coronary microvascular flux rate reserve (regadenoson stress: rest ratio).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Acute type I myocardial infarction (NSTEMI or STEMI)
Reperfusion therapy planned or performed within prior 48 hrs
Carotid or femoral artery plaque at baseline, or carotid intima media thickness >1.5 mm

Exclusion Criteria:

Type II MI
Failed primary PCI or need for emergent bypass surgery
Severe heart failure (NYHA class IV)
Life-threatening complication of MI (myocardial rupture, ischemic VSD, papillary muscle rupture)
Refractory ventricular arrhythmias
Allergy to dapansutril, OLT177, or drugs in the same class
Co-morbidity limiting 6 month survival
Active malignancy or recent malignancy with any systemic anti-cancer treatment
Active infection
Use of immunosuppressive medications or immunodeficiency disorder
Neutropenia (ANC <2,000)
Moderate or severe renal impairment (GFR <30 ml/min)
Recent stroke (within previous 3 months)
Allergy to ultrasound enhancing agents or polyethylene glycol
Pregnancy or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Virginia	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

University of Virginia

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jonathan Lindner, MD, Professor of Medicine, Vice Chief for Research, Cardiovascular Division, University of Virginia

ClinicalTrials.gov Identifier:

NCT05880355

Other Study ID Numbers:

HSR230183

First Posted:

May 30, 2023

Last Update Posted:

May 30, 2023

Last Verified:

May 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

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.:

Additional relevant MeSH terms:

Myocardial Infarction

Infarction

Dapansutrile

Study Results

No Results Posted as of May 30, 2023