Fatty Acid Radiotracer Comparison Study in Heart Failure Patients

NCT ID: NCT01648296

Last Updated: 2020-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-13
• Study Completion Date: 2014-06-04

Brief Summary

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.

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).

Conditions

Heart Failure; Obesity; Type 2 Diabetes Mellitus; Health Normal Volunteer Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

[18F]FluorbetaOx

Intervention Type: DRUG

Fluorine 18-labeled FluorbetaOx

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.

Group Type: EXPERIMENTAL

[18F]FluorbetaOx

Intervention Type: DRUG

Fluorine 18-labeled FluorbetaOx

Interventions

[18F]FluorbetaOx

Fluorine 18-labeled FluorbetaOx

Intervention Type: DRUG

Other Intervention Names

IND #113344

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert J Gropler, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Other Identifiers

IRB#201208087

Identifier Type: OTHER

Identifier Source: secondary_id

IND113344

Identifier Type: -

Identifier Source: org_study_id