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Trial record 63 of 146 for:    epilepsy AND Bethesda

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

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ClinicalTrials.gov Identifier: NCT02230592
Recruitment Status : Completed
First Posted : September 3, 2014
Last Update Posted : July 4, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief 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. 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.

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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....


Condition or disease
Anxiety Disorder Major Depressive Disorder

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.


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Study Type : Observational
Actual Enrollment : 19 participants
Time Perspective: Prospective
Official Title: PET Imaging of Brain mGluR1 Receptors Using [18F]FIMX
Study Start Date : November 8, 2013
Actual Primary Completion Date : June 16, 2016
Actual Study Completion Date : June 16, 2016

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Ability to measure mGluR1 in brain [ Time Frame: 3 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:
  • Age 18 to 55.
  • Able to give written informed consent.

EXCLUSION CRITERIA:

  • 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.
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02230592


Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Robert B Innis, M.D. National Institute of Mental Health (NIMH)

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT02230592     History of Changes
Other Study ID Numbers: 140016
14-M-0016
First Posted: September 3, 2014    Key Record Dates
Last Update Posted: July 4, 2018
Last Verified: July 18, 2016
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
PET
Metabolic Glutamate Receptors
Brain Imaging
Additional relevant MeSH terms:
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Disease
Depressive Disorder
Depressive Disorder, Major
Anxiety Disorders
Pathologic Processes
Mood Disorders
Mental Disorders