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Spectroscopic Imaging at 4T: A Drug Challenge Study (CEBRA2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Eric Nestler Jensen, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01577706
First received: April 11, 2012
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

An advanced technique for rapid magnetic resonance proton spectroscopic imaging (1H-MRSI) will be employed in a drug challenge study in healthy volunteers to spatially map and measure acute changes in the brain chemicals GABA, glutamate and glutamine after administration of a drug. Three condition will be tested in a double-blind fashion, i)depressant, ii)stimulant, iii)placebo. It is hypothesized that unique and reproducible spatial and directional metabolic response patterns will be observed, unique to each condition within the brain.


Condition Intervention
AOD Effects and Consequences
Drug: Alprazolam
Drug: Dextroamphetamine

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Spectroscopic Imaging of GABA and Glutamate/Glutamine in Healthy Volunteers at 4T: A Double Blind, Crossover Drug Challenge Study

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Magnitude of metabolite level changes throughout the brain with separate administration of Dexedrine and Alprazolam [ Time Frame: Measures taken in 20 minute intervals for 2 hours ] [ Designated as safety issue: No ]
    The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA, glutamate and glutamine in response to an acute drug challenge. In addition to detecting changes in metabolite levels, it is anticipated that our protocol will allow us to spatially map the distribution of these changes within the brain.


Secondary Outcome Measures:
  • Spatial distribution of metabolite level changes throughout the brain with separate administration of Dexedrine and Alprazolam [ Time Frame: Measures taken in 20 minute intervals for 2 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: June 2013
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy Volunteers
Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning
Drug: Alprazolam
Alprazolam, gel-capsule, 1mg, single-dose, 1-day
Other Name: Xanax
Drug: Dextroamphetamine
Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day
Other Name: Dexedrine

Detailed Description:

Proton magnetic resonance spectroscopy (1H MRS) is a powerful tool for assessing neurochemistry non-invasively in vivo. However, the primary shortcoming in most studies is the lack of spatial coverage afforded by the typical single-voxel design. Limits on participant tolerance and financial resources restrict single-voxel studies to an examination of one or two carefully chosen voxels per scan, thus inadequately addressing the question of focal vs. global pathophysiology. A secondary shortcoming is that most studies report on either GABA or glutamate-glutamine (Glu-Gln) due to the technically demanding spectral-editing techniques that must be implemented in order to resolve and quantify those metabolites with any accuracy.

1H MRS imaging (MRSI) can partially overcome these limitations by providing a global picture of brain chemistry rather than just the focal snapshot afforded by the single-voxel design. However, the scan time necessary for collecting enough data for adequate spatial resolution and signal-to-noise, particularly if also using specialized spectral-editing techniques, is still too lengthy. We recently developed a method that combines Spectroscopic Imaging with the MEGAPRESS-based difference-editing acquisition for optimal GABA detection as well as for optimal detection of Glu and Gln. This MEGACSI sequence will permit us to obtain the maximum amount of neurochemical information in a clinically sound scan time, while using the current state-of-the-art MRS editing methods for optimal detection of GABA, Glu, and Gln.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participants will be male volunteers between the ages of 21-45
  • Non-smoking participants are preferred, but will admit those who smoke less than 5 cigarettes per day
  • Participants must be able to read screening materials including consent form and give informed consent

Exclusion Criteria:

  • Participants cannot meet DSM-IV criteria for lifetime and/or current mood, anxiety, psychotic, and alcohol/drug use disorders as identified by the SCID
  • Participants cannot be taking any prescription medication (except oral contraceptives, certain short-term anti-fungal agents, and some topical creams for dermal conditions) or nutritional supplements
  • Participants cannot be taking any psychotropic medications
  • Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders.
  • Participants cannot have any conditions that are contraindicated for MRI
  • Participants cannot have a family history of alcoholism
  • Participants cannot have any abnormal blood chemistries/urinalysis results or any other medical condition that may affect drug disposition (e.g., Hepatitis C)
  • Participants cannot have current or past cardiac problems, and they also cannot have a family history of sudden death or ventricular arrhythmia
  • Participants who, in the investigators' judgment, will not likely be able to comply with the study protocol.
  • Participants cannot have any clinically significant findings in the structural anatomic brain scans (per the MRI report read by a board-certified radiologist).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01577706

Locations
United States, Massachusetts
McLean Imaging Center, McLean Hospital
Belmont, Massachusetts, United States, 02478-9106
Sponsors and Collaborators
Mclean Hospital
Investigators
Principal Investigator: John E Jensen, Ph.D. Mclean Hospital
  More Information

No publications provided

Responsible Party: John Eric Nestler Jensen, Associate Biophysicist, Director-High Field Imaging and Spectroscopy Program, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01577706     History of Changes
Other Study ID Numbers: 2012P000197
Study First Received: April 11, 2012
Last Updated: March 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mclean Hospital:
GABA
glutamate
glutamine
spectroscopy
brain
imaging
alprazolam
dextroamphetamine
placebo

Additional relevant MeSH terms:
Alprazolam
Dextroamphetamine
Anti-Anxiety Agents
Central Nervous System Agents
Central Nervous System Depressants
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 25, 2014