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Fatty Acid Radiotracer Comparison Study in Heart Failure Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
Robert Gropler, Washington University
ClinicalTrials.gov Identifier:
NCT01648296
First received: July 11, 2012
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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.

Condition Intervention Phase
Heart Failure
Obesity
Type 2 Diabetes Mellitus
Health Normal Volunteer Subjects
Drug: [18F]FluorbetaOx
Phase 0

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 28
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)
Arms Assigned Interventions
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 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.
Drug: [18F]FluorbetaOx
Fluorine 18-labeled FluorbetaOx
Other Name: IND #113344

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).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01648296

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Robert Gropler
Washington University School of Medicine
Investigators
Principal Investigator: Robert J Gropler, M.D. Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Robert Gropler, Professor of Radiology, Medicine, and Biomedical Engineering, Washington University
ClinicalTrials.gov Identifier: NCT01648296     History of Changes
Other Study ID Numbers: IND113344, IRB#201208087
Study First Received: July 11, 2012
Last Updated: March 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Heart Failure
Obesity
Type 2 Diabetes Mellitus
Health Normal Volunteer Subjects

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Heart Failure
Obesity
Body Weight
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Heart Diseases
Metabolic Diseases
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms

ClinicalTrials.gov processed this record on November 27, 2014