Clinical trial NCT02385877: Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines
Official title: Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines for Quantification of Regional Cardiac Sympathetic Nerve Density With PET
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Autonomic Peripheral Nervous System Diseases
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2015-03-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to perform first-in-human PET imaging studies of two new cardiac sympathetic nerve imaging agents, 4-\[18F\]fluoro-meta-hydroxyphenethylguanidine (\[18F\]4F-MHPG) and 3-\[18F\]fluoro-para-hydroxyphenethylguanidine (\[18F\]3F-PHPG).

Detailed description: In this study, PET imaging studies of two structurally related 18F-hydroxyphenethylguanidines, 4-\[18F\]fluoro-meta-hydroxyphenethylguanidine (\[18F\]4F-MHPG) and 3-\[18F\]fluoro-para-hydroxyphenethylguanidine (\[18F\]3F-PHPG) will be performed. All studies will be performed in normal healthy volunteers.

PET stands for Positron Emission Tomography which is a type of imaging that uses a radioactive tracer. This is also called a radiotracer which is a compound linked to a radioactive element. Most compounds are short-lived, meaning that the radioactivity breaks down quickly or is excreted from the body.

In the first stage of the study, dynamic PET imaging for 90 min will be done with \[18F\]4F-MHPG (n = 4) and \[18F\]3F-PHPG (n = 4).

Data from these studies will assess each radiotracer's imaging properties, pharmacokinetics and metabolic breakdown in plasma. Application of tracer kinetic analysis methods to the kinetics of each tracer in heart and plasma will be studied to see if these methods can provide accurate measurements of regional nerve sympathetic nerve density in the hearts of human subjects. Results from these initial studies will be used to select the lead compound for further studies in patient populations.

In the second stage of the study, whole-body PET imaging studies (n = 4) with the selected lead radiotracer will be performed to acquire data necessary for generating more accurate human radiation absorbed dose estimates.

Eligibility criteria: Inclusion Criteria:

* Non-obese (BMI \< 30)
* Normal blood pressure
* Normal blood lipid profile
* No history of prior cardiovascular disease
* Not susceptible to claustrophobia
* Ability to lay flat for 90 min

Exclusion Criteria:

* Obesity (BMI \> 30)
* Risk factors for heart disease (age \> 55y, hypertension, smoking, high blood pressure, high cholesterol levels, diabetes, etc.)
* History of heart disease (heart attack, atrial fibrillation, ventricular tachycardia, exertional angina)
* Currently using certain medications that may interact with cardiac nerves (antidepressants, cold medications, nasal decongestants, monoamine oxidase inhibitors, etc.)
* Claustrophobia
* Inability to lie flat for 90 min
* Pregnant or breast feeding

Primary outcomes:
measure: Composite measure 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, in minutes) of [18F]4F-MHPG and [18F]3F-PHPG in healthy subjects.
timeFrame: 3 months
Secondary outcomes:
measure: Radiation Dose
timeFrame: 1 year
measure: Number of Adverse Events
timeFrame: 30 days
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: David M Raffel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raffel DM, Jung YW, Koeppe RA, Jang KS, Gu G, Scott PJH, Murthy VL, Rothley J, Frey KA. First-in-Human Studies of [18F] Fluorohydroxyphenethylguanidines. Circ Cardiovasc Imaging. 2018 Dec;11(12):e007965. doi: 10.1161/CIRCIMAGING.118.007965.