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

NCT02669563 | Completed Early Phase 1

• 1 other identifier: HUM00105110
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (2)

• Quantitative measures of regional cardiac sympathetic nerve density in patients with heart failure using tracer kinetic analyses.

  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.

  Up to 30 days after [18F]4F-MHPG or [18F]3F-PHPG injection.

Study Arms (2)

Stage 1

EXPERIMENTAL

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; Drug: [18F]3F-PHPG; Drug: [13N]ammonia

Stage 2

EXPERIMENTAL

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; Drug: [18F]3F-PHPG; Drug: [13N]ammonia; Drug: [11C]HED

Interventions

[18F]4F-MHPG DRUG

IV injection of \[18F\]4F-MHPG

Also known as: 4-[18F]fluoro-meta-hydroxyphenethylguanidine

Stage 1; Stage 2

[18F]3F-PHPG DRUG

IV injection of \[18F\]3F-PHPG

Also known as: 3-[18F]fluoro-para-hydroxyphenethylguanidine

Stage 1; Stage 2

[13N]ammonia DRUG

IV injection of \[13N\]ammonia

Also known as: [13N]NH3

Stage 1; Stage 2

[11C]HED DRUG

IV injection of \[11C\]HED

Also known as: [11C]meta-hydroxyephedrine

Stage 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Raffel DM, Crawford TC, Jung YW, Koeppe RA, Gu G, Rothley J, Frey KA. Quantifying cardiac sympathetic denervation: first studies of 18F-fluorohydroxyphenethylguanidines in cardiomyopathy patients. Eur J Nucl Med Mol Imaging. 2022 Jan;49(2):619-631. doi: 10.1007/s00259-021-05517-7. Epub 2021 Aug 13.

  PMID: 34387718 DERIVED

MeSH Terms

Conditions

Cardiomyopathies

Interventions

4-fluoro-3-hydroxyphenethylguanidine; 3-hydroxyephedrine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• David M Raffel, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Professor

Study Record Dates

• First Submitted: January 22, 2016
• First Posted: February 1, 2016
• Study Start: December 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 27, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)