Imaging Histone Deacetylase in the Heart

Diabetes Clinical Trial

Official title:

Imaging of Histone Deacetylase in the Heart

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03549559
• Other study ID #: 1R01HL141563
• Status: Recruiting
• Phase: N/A
• Start date: September 7, 2018
• Est. completion date: July 1, 2023

Study information

• Verified date: March 2022
• Source: Massachusetts General Hospital
• Contact: David E Sosnovik, MD
• Phone: 617-724-3407
• Email: dsosnovik[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: July 1, 2023
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• 11C-Martinostat
Imaging probe for evaluating the activity of histone deacetylase in the heart

Device:
• PET-MRI
Siemens PET-MR Scanner (Biograph MMR)

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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