Imaging Histone Deacetylase in the Heart

Purpose

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.

Conditions

  • Heart Failure With Normal Ejection Fraction
  • Left Ventricular Hypertrophy
  • Aortic Valve Stenosis
  • Diabetes

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

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 Design

Phase
N/A
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Diagnostic
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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)

Recruiting Locations

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
Contact:
David Sosnovik, MD

More Details

Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

David E Sosnovik, MD
617-724-3407
dsosnovik@mgh.harvard.edu

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.