An Exploratory Study of 18F-Labeled Hydroxyphenethylguanidines in Heart Failure Patients

February 23, 2017 updated by: David M. Raffel, Ph.D., University of Michigan

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18-80y
  • Cardiomyopathy (ischemic and non-ischemic)
  • Left ventricular ejection fraction (LVEF) < 35%
  • Clinically appropriate referral for surgical implantation of an implantable cardiodefibrillator (ICD) for primary prevention of sudden cardiac death
  • Not claustrophobic
  • Ability to lie flat for 90 min
  • Give informed consent

Exclusion Criteria:

  • Revascularization such as the placement of a stent or balloon angioplast in the preceding 40 days
  • Renal dysfunction with eGFR < 50 mL/min/1.73 m2

  • Currently taking medications or drugs that may alter PET scans of cardiac sympathetic nerve terminals with these tracers, including any of the following:

    • Tricyclic antidepressants, which inhibit the norepinephrine transporter, such as amitriptyline, desipramine, imipramine, etc.
    • Cold medications (e.g., Sudafed®, as they may contain sympathomimetic amines, such as phenylephrine, phenylpropanolamine, pseudoephedrine, etc.)
    • Nasal decongestants (some use phenylephrine as the active agent)
    • Cocaine (which inhibits the norepinephrine transporter)
    • Tetrabenazine (Xenazine, which inhibits VMAT2 transporters on vesicles inside neurons)
    • Monoamine oxidase inhibitors (MAOI)
    • Some antihypertensive drugs (reserpine, labetalol, α-methyldopa, and clonidine)
  • Pregnancy or lactation
  • Claustrophobia
  • Inability to lie flat for 90 min

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stage 1

Subjects (n = 4 to 10) will be injected once with 20 mCi of [13N]ammonia and receive a 20 minute PET scan. They will then be injected once with 6.5 mCi of one of the two new drugs under study, [18F]4F-MHPG or [18F]3F-PHPG, and receive a 60 minute PET scan.

On a second visit to the clinic, subjects will be injected once with 6.5 mCi of [18F]3F-PHPG or [18F]4F-MHPG (whichever was not used for the first visit) and receive a 60 minute PET scan.
Drug: [18F]4F-MHPG
IV injection of [18F]4F-MHPG
Other Names:
  • 4-[18F]fluoro-meta-hydroxyphenethylguanidine
Drug: [18F]3F-PHPG
IV injection of [18F]3F-PHPG
Other Names:
  • 3-[18F]fluoro-para-hydroxyphenethylguanidine
Drug: [13N]ammonia
IV injection of [13N]ammonia
Other Names:
  • [13N]NH3
Experimental: Stage 2

Subjects (n = 20 to 26) will be injected with 20 mCi of [13N]ammonia and receive a 20 minute PET scan.

They will then be injected once with 6.5 mCi of [18F]4F-MHPG or [18F]3F-PHPG (whichever was chosen based on Stage 1 of the study) and receive a 60 minute PET scan. On a second visit to the clinic, subjects will be injected once with 20 mCi of [11C]HED and receive a 40 minute scan.
Drug: [18F]4F-MHPG
IV injection of [18F]4F-MHPG
Other Names:
  • 4-[18F]fluoro-meta-hydroxyphenethylguanidine
Drug: [18F]3F-PHPG
IV injection of [18F]3F-PHPG
Other Names:
  • 3-[18F]fluoro-para-hydroxyphenethylguanidine
Drug: [13N]ammonia
IV injection of [13N]ammonia
Other Names:
  • [13N]NH3
Drug: [11C]HED
IV injection of [11C]HED
Other Names:
  • [11C]meta-hydroxyephedrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite measures based on radiotracer tissue uptake ratios (heart-to-lung ratio, heart-to-liver ratio, heart-to-blood ratio) and rates of metabolism in plasma (half-time, minutes) of [18F]4F-MHPG and [18F]3F-PHPG in patients with heart failure.
Time Frame: 12 months
These data on the relative imaging properties and metabolism of [18F]4F-MHPG and [18F]3F-PHPG in heart failure patients will be used to select the lead radiotracer for further clinical development.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative measures of regional cardiac sympathetic nerve density in patients with heart failure using tracer kinetic analyses.
Time Frame: 36 months
Robust metrics of regional sympathetic nerve density in the heart obtained using tracer kinetic analysis techniques, including compartmental modeling and Patlak graphical analysis, will contribute to selection of a lead radiotracer.
36 months
Number of study participants with adverse events as a measure of safety and tolerability following intravenous administration of [18F]4F-MHPG or [18F]3F-PHPG.
Time Frame: Up to 30 days after [18F]4F-MHPG or [18F]3F-PHPG injection.
Assessments of the safety of [18F]4F-MHPG and [18F]3F-PHPG as PET radiopharmaceuticals for routine studies in patients.
Up to 30 days after [18F]4F-MHPG or [18F]3F-PHPG injection.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Investigators

  • Principal Investigator: David M Raffel, PhD, University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

January 22, 2016

First Submitted That Met QC Criteria

January 26, 2016

First Posted (Estimate)

February 1, 2016

Study Record Updates

Last Update Posted (Actual)

February 27, 2017

Last Update Submitted That Met QC Criteria

February 23, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00105110

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cardiomyopathy

Clinical Trials on [18F]4F-MHPG

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mexico

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe