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Anxiety DisorderNCT02230592

PET Imaging of Brain mGluR1 Receptors Using [18F]FIMX

An observational study of Anxiety Disorder and Major Depressive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Objective: Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Anxiety Disorder, Major Depressive Disorder
How many people
19 participants
Where
1 siteUnited States
Study dates
8 Nov 2013to 16 Jun 2016
Phase
Observational
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

  • Age 18 to 55.
  • Able to give written informed consent.

Who cannot join

  • Any current Axis I diagnosis.
  • Clinically significant laboratory abnormalities.
  • Positive HIV test.
  • Unable to have an MRI scan.
  • History of neurologic illness or injury with the potential to affect study data interpretation.
  • Recent exposure to radiation (i.e. PET from other research) that, when combined with this study, would be above the allowable limits.
Show all 11Show fewer
  • Inability to lie flat on camera bed for at least two hours.
  • Pregnancy or breast feeding.
  • Able to get pregnant but does not use birth control.
  • History of drug or alcohol abuse within 6 months or a history of alcohol or drug dependence (excepting nicotine) within 3 years
  • Exclusion criteria for the dosimetry subjects are the same as reported above, with the exception of MRI contraindications, because an MRI will not be performed in these subjects.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Objective:

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum, hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increased intracellular calcium levels. Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would impact clinical management of brain disorders characterized by disruptions in glutamatergic transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been hindered by the lack of high affinity and selective ligands for this receptor subtype.

Read more

The present protocol will evaluate the ability of a new PET ligand, [18F]FIMX, to image and quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases:

  1. Phase 0: screening whole-body scan;
  2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent measurement of the parent radioligand in arterial plasma;
  3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed doses of [18F]FIMX by performing whole body imaging;
  4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma.

Study Population:

Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or whole-body imaging..

Design:

This study will begin with a screening whole-body scan to confirm that the radioactivity has fairly broad distribution in several organs. For absolute quantification of mGluR1, 22 healthy controls will have brain PET imaging using [18F]FIMX and an arterial line. Up to 12 of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry, which does not require an arterial line.

<TAB>

Outcome Measures

To assess absolute quantitation of mGluR1 with [18F]FIMX, we will primarily use two outcome measures: the identifiability and time stability of distribution volume calculated with compartmental modeling. In test-retest study, we will calculate the retest variability. To assess whole-body biodistribution and dosimetry of [18F]FIMX we will use the organ time-activity curves....

Read the detailed description

Objective:

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum, hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increased intracellular calcium levels. Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would impact clinical management of brain disorders characterized by disruptions in glutamatergic transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been hindered by the lack of high affinity and selective ligands for this receptor subtype.

The present protocol will evaluate the ability of a new PET ligand, [18F]FIMX, to image and quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases:

  1. Phase 0: screening whole-body scan;
  2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent measurement of the parent radioligand in arterial plasma;
  3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed doses of [18F]FIMX by performing whole body imaging;
  4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma.

Study Population:

Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or whole-body imaging.

Design:

This study will begin with a screening whole-body scan to confirm that the radioactivity has fairly broad distribution in several organs. For absolute quantification of mGluR1, 22 healthy controls will have brain PET imaging using [18F]FIMX and an arterial line. Up to 12 of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry, which does not require an arterial line.

<TAB>

Outcome Measures

To assess absolute quantitation of mGluR1 with [18F]FIMX, we will primarily use two outcome measures: the identifiability and time stability of distribution volume calculated with compartmental modeling. In test-retest study, we will calculate the retest variability. To assess whole-body biodistribution and dosimetry of [18F]FIMX we will use the organ time-activity curves.

Keywords
PET, Metabolic Glutamate Receptors, Brain Imaging
Medical subject headings
Anxiety Disorders, Depressive Disorder, Major

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ability to measure mGluR1 in brain

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2014 (estimated)
  2. Study start8 Nov 2013
  3. Primary completion16 Jun 2016
  4. Study completion16 Jun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Time perspective
Prospective
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02230592
Sponsor's protocol ID
140016
Other IDs
14-M-0016
Status last verified
18 Jul 2016
First submitted
28 Aug 2014
Last updated
5 Jul 2018
Results posted
No

Publications

  • Anwyl R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev. 1999 Jan;29(1):83-120. doi: 10.1016/s0165-0173(98)00050-2.

    PubMed 9974152

  • Battaglia G, Bruno V, Pisani A, Centonze D, Catania MV, Calabresi P, Nicoletti F. Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission. Mol Cell Neurosci. 2001 Jun;17(6):1071-83. doi: 10.1006/mcne.2001.0992.

    PubMed 11414795

  • Bordi F, Ugolini A. Group I metabotropic glutamate receptors: implications for brain diseases. Prog Neurobiol. 1999 Sep;59(1):55-79. doi: 10.1016/s0301-0082(98)00095-1.

    PubMed 10416961

  • Veronese M, Zanotti-Fregonara P, Rizzo G, Bertoldo A, Innis RB, Turkheimer FE. Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot. Neuroimage. 2016 Apr 15;130:1-12. doi: 10.1016/j.neuroimage.2016.01.058. Epub 2016 Feb 2.

    PubMed 26850512

  • Zanotti-Fregonara P, Xu R, Zoghbi SS, Liow JS, Fujita M, Veronese M, Gladding RL, Rallis-Frutos D, Hong J, Pike VW, Innis RB. The PET Radioligand 18F-FIMX Images and Quantifies Metabotropic Glutamate Receptor 1 in Proportion to the Regional Density of Its Gene Transcript in Human Brain. J Nucl Med. 2016 Feb;57(2):242-7. doi: 10.2967/jnumed.115.162461. Epub 2015 Oct 29.

    PubMed 26514176

Questions about this trial

What is this clinical trial studying?

An observational study of Anxiety Disorder and Major Depressive Disorder, run by National Institute of Mental Health (NIMH) 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 2 inclusion and 11 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 5 Jul 2018. 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.

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?

Ability to measure mGluR1 in brain (time frame: 3 years). 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 NCT02230592, which also lists 5 linked publications.

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 5 Jul 2018.

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