Aortic Valve Stenosis, Diabetes, Heart Failure With Normal Ejection Fraction, Left Ventricular Hypertrophy
Conditions
Brief summary
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.
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.
Interventions
DRUG11C-Martinostat
Imaging probe for evaluating the activity of histone deacetylase in the heart
DEVICEPET-MRI
Siemens PET-MR Scanner (Biograph MMR)
Sponsors
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 11C-Martinostat Binding | 10-60 minutes post-injection | 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 |
Countries
United States
Contacts
Primary ContactDavid E Sosnovik, MD
Backup ContactAnne L Philip, MPH
Outcome results
None listed