Autonomic Peripheral Nervous System DiseasesEarly Phase 1NCT02385877
Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines
A Early Phase 1 study testing [18F]4F-MHPG and [18F]3F-PHPG in people with Autonomic Peripheral Nervous System Diseases, run by University of Michigan at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Autonomic Peripheral Nervous System Diseases
- What is being tested?
- [18F]4F-MHPG and [18F]3F-PHPG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Aug 2016
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines for Quantification of Regional Cardiac Sympathetic Nerve Density With PET
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).
Read the 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.
- Being tested
- [18F]4F-MHPG, [18F]3F-PHPG
- Medical subject headings
- Autonomic Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]4F-MHPGDrug
Also called 4-[18F]fluoro-meta-hydroxyphenethylguanidine
IV injection of [18F]4F-MHPG
[18F]3F-PHPGDrug
Also called 3-[18F]fluoro-para-hydroxyphenethylguanidine
IV injection of [18F]3F-PHPG
| Study group | Role | What they receive |
|---|---|---|
| Protocol 1: [18F]4F-MHPG | Experimental | Subjects (n = 4) will be injected one time with 6.5 mCi of 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and receive a 90 minute PET scan. Receives: Drug: [18F]4F-MHPG |
| Protocol 1: [18F]3F-PHPG | Experimental | Subjects (n = 4) will be injected one time with 6.5 mCi of 3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG) and receive a 90 minute PET scan. Receives: Drug: [18F]3F-PHPG |
| Protocol 2: Biodistribution Studies | Experimental | Subjects (n = 4) will be injected one time with 6.5 mCi of either [18F]4F-MHPG or [18F]3F-PHPG (whichever is selected based on Protocol 1 studies) and receive four whole-body PET scans, starting at 5 min, 60 min, 150 min and 360 min after tracer injection. Receives: Drug: [18F]4F-MHPG; Drug: [18F]3F-PHPG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (2)
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.
Measured: 1 year
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
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autonomic Peripheral Nervous System DiseasesStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David M. Raffel, Ph.D., University of Michigan
- Investigators
- David M Raffel, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02385877
- Sponsor's protocol ID
- HUM00088601
- Status last verified
- Jun 2017
- First submitted
- 25 Feb 2015
- Last updated
- 2 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 30558502
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines for Quantification of Regional Cardiac Sympathetic Nerve Density With PET
- ClinicalTrials.gov ID
- NCT02385877
- Acronym / sponsor ID
- HUM00088601
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- Mar 2015 (actual)
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 11 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Protocol 1: [18F]4F-MHPG | Experimental | Drug: [18F]4F-MHPGSubjects (n = 4) will be injected one time with 6.5 mCi of 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and receive a 90 minute PET scan. |
| Protocol 1: [18F]3F-PHPG | Experimental | Drug: [18F]3F-PHPGSubjects (n = 4) will be injected one time with 6.5 mCi of 3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG) and receive a 90 minute PET scan. |
| Protocol 2: Biodistribution Studies | Experimental | Drug: [18F]4F-MHPG, Drug: [18F]3F-PHPGSubjects (n = 4) will be injected one time with 6.5 mCi of either [18F]4F-MHPG or [18F]3F-PHPG (whichever is selected based on Protocol 1 studies) and receive four whole-body PET scans, starting at 5 min, 60 min, 150 min and 360 min after tracer injection. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Non-obese (BMI < 30)
- Normal blood pressure
- Normal blood lipid profile
- No history of prior cardiovascular disease
- Not susceptible to claustrophobia
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]4F-MHPGAlso: 4-[18F]fluoro-meta-hydroxyphenethylguanidineIV injection of [18F]4F-MHPG | Drug | Protocol 1: [18F]4F-MHPG, Protocol 2: Biodistribution Studies |
| [18F]3F-PHPGAlso: 3-[18F]fluoro-para-hydroxyphenethylguanidineIV injection of [18F]3F-PHPG | Drug | Protocol 1: [18F]3F-PHPG, Protocol 2: Biodistribution Studies |
Primary outcome
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.
Time frame: 3 months
These data will be used to select the lead radiotracer for further clinical development.
2 secondary outcomes
Radiation Dose
Time frame: 1 year
Number of Adverse Events
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Derived from this study: PubMed 30558502Raffel 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David M Raffel, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing [18F]4F-MHPG and [18F]3F-PHPG in people with Autonomic Peripheral Nervous System Diseases, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02385877, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.