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Imaging Histone Deacetylase in the Heart

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ClinicalTrials.gov Identifier: NCT03549559
Recruitment Status : Not yet recruiting
First Posted : June 8, 2018
Last Update Posted : June 13, 2018
Sponsor:
Information provided by (Responsible Party):
David E Sosnovik, Massachusetts General Hospital

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : July 1, 2018
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2023


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)




Primary Outcome Measures :
  1. 11C-Martinostat Binding [ Time Frame: 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



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03549559


Contacts
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Contact: David E Sosnovik, MD 617-724-3407 dsosnovik@mgh.harvard.edu
Contact: Anne L Philip, MPH 617-726-0431 alphilip@mgh.harvard.edu

Sponsors and Collaborators
Massachusetts General Hospital

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Responsible Party: David E Sosnovik, Associate Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03549559     History of Changes
Other Study ID Numbers: 1R01HL141563 ( U.S. NIH Grant/Contract )
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: June 13, 2018
Last Verified: June 2018

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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:
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Heart Failure
Hypertrophy
Aortic Valve Stenosis
Hypertrophy, Left Ventricular
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Heart Valve Diseases
Ventricular Outflow Obstruction
Cardiomegaly