Imaging Histone Deacetylase in the Heart

Imaging of Histone Deacetylase in the Heart

The overall goal of this PET-MR imaging trial is to evaluate 11C-Martinostat, a histone deacetylase targeted radioligand, in patients with aortic stenosis, individuals with diabetes, and healthy volunteers.

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Aortic Valve Stenosis; Heart Failure With Normal Ejection Fraction; Left Ventricular Hypertrophy
• Intervention / Treatment: Drug: 11C-Martinostat; Device: PET-MRI

Detailed Description

Histone deacetylases (HDACs), a class of epigenetic enzymes, play an important role in the pathophysiology of heart failure, including development of left ventricular hypertrophy and myocardial fibrosis. Preclinical data demonstrate the importance of HDAC inhibition in attenuating these pathological processes and maintaining the integrity of the myocardium. However, the role of HDACs in the human heart, and the utility of HDAC inhibition remains unknown. Therefore, a noninvasive method to detect HDAC activity in the human heart in healthy individuals and patients with heart disease may be of major medical and public health value to help determine prognosis, direct therapy, and guide the development of novel therapies for heart failure. The investigators have recently developed a novel radiotracer, 11C-Martinostat, which binds with high affinity to class I HDACs. The objective of this protocol is to assess the utility of 11C-Martinostat PET-MR to detect HDAC expression in the hearts of healthy individuals and patients with severe aortic stenosis or diabetes.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David E Sosnovik, MD; Phone Number: 617-724-3407; Email: dsosnovik@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: David Sosnovik, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Group 1: Healthy Volunteers (n = 30)

• Healthy adults with no known history of medical disease
• Age 18-85 years
• No history cardiovascular disease
• Ability to provide informed consent

Group 2: Patients with Diabetes (n = 16)

• Age 18-85 years
• Diagnosis of diabetes
• Echocardiogram within last 12 months showing no evidence of left ventricular hypertrophy or hemodynamic findings consistent with heart failure with preserved ejection fraction
• Ability to provide informed consent

Group 3: Patients with Aortic Stenosis (n = 50)

• Age 18-85 years
• Echocardiogram or cardiac MRI scan within last 12 months documenting left ventricular hypertrophy and degenerative calcific aortic stenosis
• Ability to provide informed consent

Exclusion Criteria:

• Known contraindication to MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Healthy Subjects; Healthy subjects will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI.	Drug: 11C-Martinostat; Imaging probe for evaluating the activity of histone deacetylase in the heart; Device: PET-MRI; Siemens PET-MR Scanner (Biograph MMR)
ACTIVE_COMPARATOR: Diabetes Patient Subjects; Patient subjects with diabetes will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI.	Drug: 11C-Martinostat; Imaging probe for evaluating the activity of histone deacetylase in the heart; Device: PET-MRI; Siemens PET-MR Scanner (Biograph MMR)
EXPERIMENTAL: Aortic Stenosis Patient Subjects; Patient subjects with aortic stenosis will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI before and after transcatheter valve replacement.	Drug: 11C-Martinostat; Imaging probe for evaluating the activity of histone deacetylase in the heart; Device: PET-MRI; Siemens PET-MR Scanner (Biograph MMR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
11C-Martinostat Binding	Comparison of regional HDAC activity as measured by standard uptake value ratio (SUVR) of 11C-Martinostat between patient subjects with aortic stenosis or diabetes and healthy volunteers	10-60 minutes post-injection

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 7, 2018
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): July 1, 2023

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: May 25, 2018
• First Posted (ACTUAL): June 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Cardiomegaly; Aortic Valve Stenosis; Hypertrophy; Hypertrophy, Left Ventricular
• Other Study ID Numbers: 1R01HL141563 (NIH)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No