Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines

Autonomic Peripheral Nervous System Diseases Clinical Trial

Official title:

Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines for Quantification of Regional Cardiac Sympathetic Nerve Density With PET

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02385877
• Other study ID #: HUM00088601
• Status: Completed
• Phase: Early Phase 1
• First received: February 25, 2015
• Last updated: June 30, 2017
• Start date: March 2015
• Est. completion date: August 2016

Study information

• Verified date: June 2017
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• Autonomic Peripheral Nervous System Diseases
• Nervous System Diseases
• Peripheral Nervous System Diseases

Intervention

Drug:
• [18F]4F-MHPG
IV injection of [18F]4F-MHPG
• [18F]3F-PHPG
IV injection of [18F]3F-PHPG

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	These data will be used to select the lead radiotracer for further clinical development.	3 months
Secondary	Radiation Dose	Human radiation absorbed dose estimates based on the kinetics of the selected lead radiotracer in various organs, as extracted from whole-body PET scans.	1 year
Secondary	Number of Adverse Events	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	30 days