Fatty Acid Radiotracer Comparison Study in Heart Failure Patients
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:
- To assess the diagnostic quality of [18F]FluorbetaOx PET images and kinetics at the proposed 10 millicurie (mCi) dose.
- To quantitatively determine the relationship between PET measurements of myocardial FA metabolism obtained with [18F]FluorbetaOx and those using [11C]Palmitate.
- To calculate human dosimetry based on the human biodistribution of [18F]FluorbetaOx.
- 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.
Type 2 Diabetes Mellitus
Health Normal Volunteer Subjects
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||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|
- 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. [ Time Frame: 24-72 hrs. and and 6 months post [18F]FluorbetaOx injection ] [ Designated as safety issue: Yes ]The primary endpoint is to determine if PET/CT measurements of myocardial FA metabolism performed with [18F]FluorbetaOx correlates with those performed with [11C]Palmitate. To this end parameter estimates of myocardial FA uptake, oxidation and esterification determined from the myocardial kinetics of [18F]FluorbetaOx will be compared those obtained with [11C]palmitate using standard correlation analyses. Human dosimetry of [18F]FluorbetaOx will be calculated based on the first 8 DCM +/-T2DM patients and 4 normal healthy volunteers. The changes in vital signs and clinical laboratory tests will be listed to evaluate the safety of [18F]FluorbetaOx -PET/CT.
- To determine human dosimetry based on the human biodistribution of [18F](+/-)NOS in both normal healthy volunteers and dilated non-ischemic cardiomyopathy patients. [ Time Frame: 2-3 days post [18F]FluorbetaOx injection ] [ Designated as safety issue: Yes ]A total of 12 subjects (Four normal healthy volunteer subjects and 8 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.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
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.
Fluorine 18-labeled FluorbetaOx
Other Name: 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.
Fluorine 18-labeled FluorbetaOx
Other Name: IND #113344
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01648296
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Robert J Gropler, M.D.||Washington University School of Medicine|