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Trial record 64 of 146 for:    epilepsy AND Bethesda

Evaluation of a Novel Positron Emission Tomography (PET Radiotracer for TARP Gamma-8

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ClinicalTrials.gov Identifier: NCT02108015
Recruitment Status : Terminated
First Posted : April 9, 2014
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

Objective

Ionotropic glutamate receptors are ligand-gated ion channels responsible for most of the excitatory neurotransmission in the mammalian central nervous system (CNS). Based on pharmacology, they have been grouped into three subtypes-NMDA, AMPA and kainate. In recent years it has become apparent that the receptors do not function alone, but in the company of auxiliary proteins that regulate their activity [1]. Some of these have been shown to modulate AMPA receptor trafficking, gating and pharmacology and are classified as transmembrane AMPA receptor regulatory proteins, or TARPs ( >=-2, >=-3, >=-4, >=-5, >=-7, and >=-8). Genetic data indicate a possible role of TARPs in schizophrenia, depression, epilepsy, neuropathic pain, and bipolar disorder [1]. In a preclinical collaboration with Eli Lilly, we developed a promising radioligand, 18F-TARP252 to image TARP >=-8 using positron emission tomography (PET).

This protocol covers three phases:

  • Phase 1: kinetic brain imaging to quantify TARP >=-8 in brain relative to concurrent measurement of the parent radioligand in arterial plasma;
  • Phase 2: if 18F-TARP252 is successful in Phase 1, we will estimate the radiation-absorbed doses by performing whole body imaging;
  • 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 - 55) will undergo brain imaging. An additional eight healthy volunteers will undergo whole body dosimetry analysis.

Design

For quantification of TARP >=-8, 22 healthy controls will have brain PET imaging using 18F-TARP252 and an arterial line. Some of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will be used.

Outcome Measures

To assess quantitation of TARP >=-8 with 18F-TARP252, 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. We will assess whole-body biodistribution and dosimetry of 18F-TARP252 by calculating doses to organs and effective dose to the body.

...


Condition or disease Intervention/treatment Phase
Healthy Volunteers Procedure: Brain Imaging (PET) Procedure: Aterial Line Procedure: Blood Sampling Phase 1

Detailed Description:

Objective

Ionotropic glutamate receptors are ligand-gated ion channels responsible for most of the excitatory neurotransmission in the mammalian central nervous system (CNS). Based on pharmacology, they have been grouped into three subtypes-NMDA, AMPA and kainate. In recent years it has become apparent that the receptors do not function alone, but in the company of auxiliary proteins that regulate their activity [1]. Some of these have been shown to modulate AMPA receptor trafficking, gating and pharmacology and are classified as transmembrane AMPA receptor regulatory proteins, or TARPs ( >=-2, >=-3, >=-4, >=-5, >=-7, and >=-8). Genetic data indicate a possible role of TARPs in schizophrenia, depression, epilepsy, neuropathic pain, and bipolar disorder [1]. In a preclinical collaboration with Eli Lilly, we developed a promising radioligand, 18F-TARP252 to image TARP >=-8 using positron emission tomography (PET).

This protocol covers three phases:

  • Phase 1: kinetic brain imaging to quantify TARP >=-8 in brain relative to concurrent measurement of the parent radioligand in arterial plasma;
  • Phase 2: if 18F-TARP252 is successful in Phase 1, we will estimate the radiation-absorbed doses by performing whole body imaging;
  • 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 - 55) will undergo brain imaging. An additional eight healthy volunteers will undergo whole body dosimetry analysis.

Design

For quantification of TARP >=-8, 22 healthy controls will have brain PET imaging using 18F-TARP252 and an arterial line. Some of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will be used.

Outcome Measures

To assess quantitation of TARP >=-8 with 18F-TARP252, 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. We will assess whole-body biodistribution and dosimetry of 18F-TARP252 by calculating doses to organs and effective dose to the body.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Evaluation of a Novel Positron Emission Tomography (PET Radiotracer for TARP Gamma-8
Study Start Date : March 5, 2014
Actual Primary Completion Date : September 5, 2014
Actual Study Completion Date : December 1, 2016



Primary Outcome Measures :
  1. Binding of 18F-TARP252 in brain [ Time Frame: ongoing ]


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 - 55 (including 18 and 55).
  • Able to give written informed consent.
  • Healthy
  • Enrolled in 01-M-0254

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 related to research (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.
  • Drug/alcohol abuse or dependence

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): NCT02108015


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: Masahiro Fujita, M.D. National Institute of Mental Health (NIMH)