Spectroscopic Imaging at 4T: A Drug Challenge Study

NCT01577706 | Terminated Results

• 1 other identifier: 2012P000197
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

AOD Effects and Consequences

Keywords

GABA; glutamate; glutamine; spectroscopy; brain; imaging; alprazolam; dextroamphetamine; placebo

Outcome Measures

Primary Outcomes (7)

• Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge

  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 in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint

  from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)

• Left Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge

  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 in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint

  from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)

• Left Temporal: Percent Change in GABA Levels After an Acute Drug Challenge

  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 in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint

  from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)

• Parieto-Occipital: Percent Change in GABA Levels After an Acute Drug Challenge

  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 in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint

  from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)

• Right Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge

  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 in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint

  from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)

• Right Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge

  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 in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint

  from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)

• Right Temporal: Percent Change in GABA Levels After an Acute Drug Challenge

  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 in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100\*(later timepoint - earlier timepoint) / earlier timepoint

  from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)

Study Arms (3)

Alprazolam (A)

ACTIVE COMPARATOR

Alprazolam (Xanax), gel-capsule, 1mg, single-dose, 1-day

Drug: Alprazolam

Dextroamphetamine (D)

ACTIVE COMPARATOR

Dextroamphetamine (Dexedrine), gel-capsule, 20mg, single-dose, 1-day

Drug: Dextroamphetamine

Placebo (P)

PLACEBO COMPARATOR

Placebo gel-capsule, single-dose, 1-day

Other: Placebo

Interventions

Alprazolam DRUG

Alprazolam, gel-capsule, 1mg, single-dose, 1-day

Also known as: Xanax

Alprazolam (A)

Dextroamphetamine DRUG

Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day

Also known as: Dexedrine

Dextroamphetamine (D)

Placebo OTHER

Placebo, gel-capsule, single-dose, 1-day

Placebo (P)

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (1)

McLean Imaging Center, McLean Hospital

Belmont, Massachusetts, 02478-9106, United States

Location

MeSH Terms

Interventions

Alprazolam; Dextroamphetamine

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. J. Eric Jensen
• Organization: McLean Hospital

ejensen@mclean.harvard.edu

617-855-3366

Study Officials

• John E Jensen, Ph.D.

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Biophysicist, Director-High Field Imaging and Spectroscopy Program

Study Record Dates

• First Submitted: April 11, 2012
• First Posted: April 16, 2012
• Study Start: June 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 4, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-03

Locations

US (1)