An Exploratory Study of 18F-Labeled Hydroxyphenethylguanidines in Heart Failure Patients
Condition: Cardiomyopathy
MeSH terms: Heart Failure; Cardiomyopathies
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The main goal of this study is to test two new radioactive drugs,
      4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and
      3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG) in human subjects with congestive
      heart failure.

      Evaluations of these imaging agents will include their uptake in heart, lungs and liver,
      their metabolic breakdown in blood, and their kinetics in the heart. Based on these studies,
      the better of the two drugs will be chosen for further studies in patients with heart
      disease. After the better compound is chosen, additional measures of its imaging properties,
      metabolism and pharmacokinetics will be done in subjects with heart failure.
    

Detailed description: 
      The human heart contains many nerve fibers that are involved in controlling the heart's
      pumping function. Several heart diseases have been shown to damage the nerves in the heart.
      Studies have shown that damage to the heart nerves may be a cause of death in patients with
      diseases like heart failure or diabetes.

      Two new radioactive drugs been developed at the University of Michigan for taking pictures of
      the nerve fibers in the heart using a medical imaging method called positron emission
      tomography (PET).

      These two drugs are 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and
      3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG). Initial PET imaging studies in
      normal human subjects (see NCT 02385877) have shown that [18F]4F-MHPG and [18F]3F-PHPG are
      each able to provide a detailed regional map of the distribution of nerve fibers in the
      heart.

      In Stage 1 of this study, enrolled subjects with heart failure will undergo PET studies with
      [18F]4F-MHPG and [18F]3F-PHPG to allow direct comparison of the imaging properties,
      metabolism and pharmacokinetics of the two radioactive drugs in the same subjects.

      A third PET scan with [13N]ammonia will be done to assess resting blood flow in different
      areas of the heart. The results of these studies will be used to select the better of the two
      tracers for further study in patients with heart disease.

      In Stage 2 of the study, enrolled subjects with heart failure will undergo additional PET
      evaluations of the imaging properties and kinetics of the cardiac nerve tracer selected in
      Stage 1 (either [18F]4F-MHPG or [18F]3F-PHPG).

      Again, a PET scan with [13N]ammonia will also be performed to measure regional resting blood
      flow. A third PET scan with [11C]meta-hydroxyephedrine ([11C]HED), an established cardiac
      nerve tracer, will also be done to address research questions related to the mechanisms
      involved in the retention of [18F]4F-MHPG and [18F]3F-PHPG inside the nerve of the heart.

      For all study stages, subjects will be assessed during the scan for heart rate, blood
      pressure and oxygen saturation. Patients will be followed at 30 min, 24 hours and 30 hours
      regarding any adverse events or serious adverse events they might have experienced. These
      will be reported as required.
    

Intervention name(s): [18F]4F-MHPG; [18F]3F-PHPG; [13N]ammonia; [11C]HED
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): IV injection of [18F]4F-MHPG; IV injection of [18F]3F-PHPG; IV injection of [13N]ammonia; IV injection of [11C]HED
Other intervention name(s): 4-[18F]fluoro-meta-hydroxyphenethylguanidine; 3-[18F]fluoro-para-hydroxyphenethylguanidine; [13N]NH3; [11C]meta-hydroxyephedrine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic