Norepinephrine Transporter Availability in PTSD

September 10, 2013 updated by: Jonathon Nye, Emory University

Kinetic Modeling of Norepinephrine Transporter Availability in PTSD

The objective of this proposal is to collect pilot data to characterize the binding of [11C]MENET in combat-exposed war veterans with posttraumatic stress disorder (PTSD). Approximately two hundred thousand veterans will be returning stateside upon the end of combat operations in Iraq, and 13% of returning veterans will have PTSD. 15% of all war veterans will develop chronic PTSD symptoms requiring a lifetime of mental health care. Little is known about the dysregulation of PTSD veteran's neurochemical state including the noradrenergic system which plays a primary role in memory and stress response. This includes heightened anxiety, fear and hyperarousal symptoms characteristic of PTSD. The noradrenergic system is a concentration of neurons in the brainstem nucleus, locus coerulues, that have projections to the amygdale and prefrontal cortex. The norepinephrine transporter (NET) is responsible for regulating and terminating noradrenergic transmission, and is a specific marker for neuronal integrity. Hyperactivity of the noradrenergic system up-regulates NET protein. An unresolved problem in studying the noradrenergic system is identification of suitable radiopharmaceutical to non-invasively measure alterations in the density of NET. The investigators propose to address this challenge by using positron emission tomography (PET) to measure stress-induced changes in NET expression in combat-exposed war veterans with PTSD. The central hypothesis of this proposal is that war veterans with PTSD have an up-regulation of NET in the locus coerulues resulting from hyperactivity of the noradrenergic system compared to healthy controls. Through a series of experiments, the investigators will determine the in vivo binding characteristics of [11C]MENET. The investigators will use this information to optimally design an experimental protocol to measure the availability of NET in a pilot group of combat-exposed war veterans with PTSD. The aims of this proposal are: 1) Measure the uptake kinetics and whole brain distribution of [11C]MENET in combat-exposed veterans with PTSD and healthy controls, 2) Develop a quantitative kinetic model of [11C]MENET uptake to calculate the NET availability in brain. The subjects undergoing imaging in this work will be recruited by Dr. J. Douglas Bremner (Co-Investigator) at Emory University and Atlanta Veteran Affairs Hospital. Our long-term goal is to develop a longitudinal study framework to assess the NETs dysregulation during onset of PTSD as well as its transition to chronic lifetime PTSD.

Study Overview

Status

Status

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Completed

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

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Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • PTSD as determined by the Structural Clinical Interview for DSMIV (SCID) interview of PTSD and the Clinical Administered PTSD Scale (CAPS).
  • Veteran with history of active duty service and currently discharged from active duty service
  • Free of psychotropic medication for four weeks before the study

Exclusion Criteria:

  • History of shrapnel or other foreign bodies which would preclude MRI scanning
  • Meningitis
  • Traumatic brain injury
  • Neurological disorder or organic mental disorder
  • History of loss of consciousness
  • Current or lifetime history of alcohol abuse or substance abuse or dependence base on the SCID
  • Current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia based on the SCID
  • History of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness
  • Evidence of a major or neurological illness on physical examination or as a result of laboratory studies
  • positive urine toxicology screen
  • Current steroid use

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Healthy Controls
Posttraumatic stress disorder (PTSD) is a potentially debilitating anxiety disorder triggered when a person is exposed to a traumatic event that is beyond what is experienced in everyday life. A traumatic event may include an interpersonal event like physical or sexual assault, exposure to a disaster or accidents, combat or witnessing a traumatic event. Some symptoms of PTSD include not being able to sleep, nightmares, flashbacks of the event and having problems with memory or not being able to focus. You are being asked to volunteer because you are either 1) a normal healthy volunteer or 2) a deployed veteran or non-deployed veteran who is diagnosed with PTSD. We anticipate enrolling 16 subjects; 8 veterans with PTSD and 8 healthy volunteers without PTSD.
Drug: [C-11]MENET
PET imaging involves injecting small amounts of a radioactive material into the blood stream. The radioactive material is attached to a drug called MENET that will give information about how the brain interacts with a protein called norepinephrine (NE).
Other Names:
  • (2S,3S)-2-[alpha-(2-[11C]- methylphenoxy)phenylmethyl]morpholine([11C]MENET)
Other: Veterans with PTSD
Posttraumatic stress disorder (PTSD) is a potentially debilitating anxiety disorder triggered when a person is exposed to a traumatic event that is beyond what is experienced in everyday life. A traumatic event may include an interpersonal event like physical or sexual assault, exposure to a disaster or accidents, combat or witnessing a traumatic event. Some symptoms of PTSD include not being able to sleep, nightmares, flashbacks of the event and having problems with memory or not being able to focus. You are being asked to volunteer because you are either 1) a normal healthy volunteer or 2) a deployed veteran or non-deployed veteran who is diagnosed with PTSD. We anticipate enrolling 16 subjects; 8 veterans with PTSD and 8 healthy volunteers without PTSD.
Drug: [C-11]MENET
PET imaging involves injecting small amounts of a radioactive material into the blood stream. The radioactive material is attached to a drug called MENET that will give information about how the brain interacts with a protein called norepinephrine (NE).
Other Names:
  • (2S,3S)-2-[alpha-(2-[11C]- methylphenoxy)phenylmethyl]morpholine([11C]MENET)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Measurement of norepinephrine availability
Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 1 day
Information to be obtained are [11C]MENET PET scans including arterial blood sampling to measure blood metabolites.[11C]MENET PET images will be analyze with a full compartmental kinetic analysis. Arterial blood and reference tissue input functions will be used to calculate the distribution volume ratio and binding potential of NET availability in each group
Participants will be followed for the duration of the hospital stay, an expected average of 1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Emory University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jonathon A Nye, PhD, Emory University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 13, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 11, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00057641
  • URC-00025435 (Other Identifier: Other)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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