Autonomic Peripheral Nervous System Diseases
Conditions
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.
Interventions
DRUG[18F]4F-MHPG
IV injection of \[18F\]4F-MHPG
DRUG[18F]3F-PHPG
IV injection of \[18F\]3F-PHPG
Sponsors
University of Michigan
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 3 months | These data will be used to select the lead radiotracer for further clinical development. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiation Dose | 1 year | Human radiation absorbed dose estimates based on the kinetics of the selected lead radiotracer in various organs, as extracted from whole-body PET scans. |
| Number of Adverse Events | 30 days | 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 |
Countries
United States
Outcome results
None listed