Fatty Acid Radiotracer Comparison Study in Heart Failure Patients

Measurements of Myocardial Fatty Acid Metabolism With PET and [F-18]FluorbetaOx in Humans With Heart Failure With and Without Diabetes: Comparison With [C-11]Palmitate

A single center, open-label baseline controlled imaging study to designed to assess whether Positron Emission Tomography (PET) measurements of myocardial Fatty Acid (FA) metabolism performed with [18F]FluorbetaOx correlates with measurements using [11C]palmitate. This study involves the investigational use of a PET radioactive tracer, fluorine-18 radiolabeled fatty acid analog, [18F]FluorbetaOx designed to measure beta oxidation of fatty acids in the myocardium. The investigators propose to evaluate the feasibility of the method in heart failure patients with dilated non-ischemic cardiomyopathy (DCM) with or without type-2 diabetes mellitus (T2DM) and obese subjects (Body Mass Index of ≥ 30kg/m2) with or without T2DM and normal healthy subjects to provide a wide range of perturbations in myocardial FA metabolism.

Specific objectives include:

1. To assess the diagnostic quality of [18F]FluorbetaOx PET images and kinetics at the proposed 10 millicurie (mCi) dose.
2. To quantitatively determine the relationship between PET measurements of myocardial FA metabolism obtained with [18F]FluorbetaOx and those using [11C]Palmitate.
3. To calculate human dosimetry based on the human biodistribution of [18F]FluorbetaOx.
4. Correlate measurements of myocardial FA metabolism with changes in left ventricular (LV)structure and function performed on a clinically indicated echocardiography at 6-9 months after imaging.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Obesity; Type 2 Diabetes Mellitus; Health Normal Volunteer Subjects
• Intervention / Treatment: Drug: [18F]FluorbetaOx

Detailed Description

PET imaging will be broken down into 2 groups of subjects (dosimetry and kinetic dynamic imaging/[11C]palmitate comparison) with entry into these groups will occur simultaneously. All PET imaging will be performed with a Siemens Biograph 40 PET-CT scanner. All patients will undergo routine clinical evaluation as dictated by the treating heart failure cardiologist. The results of the PET studies will not be provided to the patient or the treating cardiologist unless, in the judgment of the Principal Investigator, the images demonstrate an unsuspected abnormality that may warrant further evaluation. Subjects will be instructed not to eat after midnight the night before the study. However, patients will be instructed to continue their heart failure and diabetic medical regimens. The morning of their PET study, subjects will have two intravenous catheters placed. One will be placed in each arm for the purpose of administering radioactive tracers ([15O]Water, [11C]Palmitate, and [18F]FluorbetaOx), drawing blood samples for safety laboratory analysis. Urine samples will be obtained along with an Electrocardiogram (ECG) and vital signs. A follow-up telephone contact will be done 2-3 days post imaging study to capture unanticipated and serious adverse events (SAEs).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between 18 and 75 years of age inclusive, at the time of signing the informed consent
• Chronic dilated cardiomyopathy of non-ischemic origin
• New York Heart Association (NYHA)Class II/III heart failure for a minimum of 6 months prior to enrollment
• Heart Failure patients with Left Ventricular Ejection Fracture less than or equal to 35%
• Obesity defined as Body Mass Index of ≥ 30kg/m2
• Type 2 Diabetes Mellitus based on standard American Diabetes Association (ADA) criteria
• Capable of giving informed consent
• Not currently pregnant or nursing: Female subjects must be either: surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), or of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of [18F] FluorbetaOx is negative

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• A recent positive pre-study drug/alcohol screen noted in medical records
• Pregnant females as determined by positive (serum or urine) human chorionic gonadotropin(hCG) test at screening or prior to dosing
• Lactating females
• Unwillingness or inability to follow the procedures outlined in the protocol
• Subject is mentally or legally incapacitated
• History of a psychiatric disorder that will affect the subject's ability to participate in the study
• Restrictive, obstructive, or infiltrative cardiomyopathy; pericardial disease; uncorrected thyroid disease (TSH) noted in medical records
• History of clinically significant coronary artery disease (CAD)including (prior (ST) elevation myocardial infarction, presence of ≥ 50% obstruction of a major coronary artery, and presence of angina)
• Contraindications to PET scanning (i.e., inability to lie flat with arms over head for up to 1½ hours; claustrophobia; current participation in research studies involving radiation exposure such that the total research-related radiation dose to the subject in any given year would exceed the Code of Federal Regulation limits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dosimetry Group; A total of 12 subjects will receive a single intravenous injection of[18F]FluorbetaOx followed by PET-CT imaging. Four normal healthy volunteer subjects and 8 subjects with or without Type 2 Diabetes Mellitus with Chronic Dilated Cardiomyopathy.	Drug: [18F]FluorbetaOx; Fluorine 18-labeled FluorbetaOx; Other Names: IND #113344
Experimental: Kinetic Dynamic Group; A total of 38 subjects will receive a single intravenous injection of [18F]FluorbetaOx, [11C]Palmitate, and [15O]Water followed by PET-CT imaging. Ten normal healthy volunteer subjects and 28 subjects with or without Type 2 Diabetes Mellitus of which 18 subjects will have Chronic Dilated Cardiomyopathy and 10 obese subjects with a Body Mass Index of ≥ 30kg/m2.	Drug: [18F]FluorbetaOx; Fluorine 18-labeled FluorbetaOx; Other Names: IND #113344

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Endpoint is to Determine if PET/CT Measurements of Myocardial FA Metabolism Performed With [18F]FluorbetaOx Correlated With Those Performed With [11C]Palmitate and Calculation of Human Dosimetry.	The values in the table represent the number of participants, specifically Dosimetry and Kinetic patients and that is how the primary endpoint is arrived at. This is how the primary endpoint is determined through PET/CT measurements of Myocardial FA metabolism with F-18 Florbeta Ox. The data intended for this Outcome Measure use PET/CT images to visualize the amount of myocardial FA metabolism appears with the radio tracer, Florbeta Ox.	24-72 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine Human Dosimetry Based on the Human Biodistribution of [18F](+/-)NOS in Both Normal Healthy Volunteers and Dilated Non-ischemic Cardiomyopathy Patients.	A total of 0 subjects (Four normal healthy volunteer subjects and0 subjects with or without Type 2 Diabetes Mellitus with Chronic Dilated Cardiomyopathy)will receive a single intravenous injection of 10 mCi of[18F]FluorbetaOx followed by PET-CT imaging at two separate time points. The difference between primary Outcome and the secondary outcome are the patients themselves. Florbeta Ox was measured in normal healthy volunteers and in non-ischemic cardiomyopathy patients through PET/CT image visualization.	2-3 days post [18F]FluorbetaOx injection

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Robert J Gropler, M.D., Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2012
• Primary Completion (Actual): June 4, 2014
• Study Completion (Actual): June 4, 2014

Study Registration Dates

• First Submitted: July 11, 2012
• First Submitted That Met QC Criteria: July 19, 2012
• First Posted (Estimate): July 24, 2012

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 21, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Heart Failure; Obesity; Type 2 Diabetes Mellitus; Health Normal Volunteer Subjects
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Heart Failure; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: IND113344; IRB#201208087 (Other Identifier: Human Research Protection Office at Washington University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No