Imaging Histone Deacetylase in the Heart

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03549559
• Collaborator: (none)
• Enrollment: 96
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 57.8
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure With Normal Ejection Fraction; Left Ventricular Hypertrophy; Aortic Valve Stenosis; Diabetes	Drug: 11C-Martinostat; Device: PET-MRI	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 96 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Imaging of Histone Deacetylase in the Heart
• Actual Study Start Date: Sep 7, 2018
• Anticipated Primary Completion Date: Jul 1, 2022
• Anticipated Study Completion Date: Jul 1, 2023

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David E Sosnovik, Associate Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03549559
• Other Study ID Numbers: 1R01HL141563
• First Posted: Jun 8, 2018
• Last Update Posted: Mar 17, 2022
• Last Verified: Mar 1, 2022

• 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
• Additional relevant MeSH terms: Aortic Valve Stenosis; Hypertrophy, Left Ventricular; Hypertrophy

Study Results

No Results Posted as of Mar 17, 2022