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PET Imaging of mGLuR5 With Drug Challenge

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01691092
First Posted: September 24, 2012
Last Update Posted: April 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Yale University
  Purpose

This study is designed to look at that involvement of a process in the brain called the glutamate system in depression. Participants will undergo a screening session, up to two functional Magnetic Resonance Imaging (fMRI) scans, and up to three Positron Emission Tomography (PET) scans, as well as cognitive testing at each scan session. For one of the PET scans, a drug (either ketamine or n-acetyl cysteine) will be administered.

Hypothesis 1: The investigators hypothesize administration of ketamine or n-acetylcysteine (NAC) will lead to a decrease in mGluR5.

Hypothesis 2: The investigators hypothesize an improvement in memory and attentional skills after drug challenge.

Hypothesis 3: The investigators hypothesize an increase in mGluR5 availability and change in MRI measures post drug challenge as compared to baseline, signifying synaptogenesis.

Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5 availability due to differences in ABP688 radiotracer infusion.


Condition Intervention
Major Depressive Disorder Post-Traumatic Stress Disorder (PTSD) Drug: Ketamine

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: PET Imaging of mGluR5 With Drug Challenge

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Change in Glutamate Levels at Baseline and After Ketamine Administration as Confirmed by Positron Emission Tomography (PET) Imaging [ Time Frame: 1st scan: 90 minute baseline scan; 2nd scan: 90 minutes, ketamine administration at start of scan; scan 3: 90 minute scan 24 hours post ketamine ]
    PET imaging obtained in healthy and Major Depressive Disorder (MDD) subjects. Glutamate levels determined by radiotracer uptake in PET images.


Enrollment: 79
Study Start Date: June 2012
Study Completion Date: February 2016
Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine
All subjects will receive ketamine
Drug: Ketamine
All subjects will receive ketamine to induce glutamate release in the brain
Other Name: ketamine IV

Detailed Description:

Aim 1: To determine the acute effect of medication-induced glutamate release on mGluR5 availability in human subjects. Hypothesis 1: We hypothesize administration of ketamine or n-acetylcysteine (NAC) will lead to a decrease in mGluR5 availability.

Aim 2: To determine if glutamate release via administration of ketamine or NAC has pro cognitive benefits.

Hypothesis 2: We hypothesize an improvement in memory and attentional skills after drug challenge.

Aim 3: To determine if there is synaptogenesis detectable by PET and MRI post ketamine or NAC within a week of drug challenge (at the time of greatest antidepressant response). Hypothesis 3: We hypothesize an increase in mGluR5 availability and change in MRI measures, post drug challenge as compared to baseline, signifying synaptogenesis.

Aim 4: To determine if there is a difference in reduction of mGluR5 availability after ketamine administration when radiotracer is administered bolus as compared to bolus to constant infusion in the same subjects (ABP688 radiotracer only).

Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5 availability due to differences in ABP688 radiotracer infusion.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18-65 years old
  • English speaking
  • No other Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnosis present, besides required as below.

Inclusion criteria for depressed subjects

  • clinical diagnosis of a current or past depressive episode
  • medication free for at least 2 weeks
  • Score >16 on Hamilton Depression Rating Scale (HDRS) if currently depressed or <11 if not currently depressed
  • treatment or non-treatment seeking who understand that this study is for research purposes only

Inclusion criteria for healthy controls

  • no current, or history of, any DSM-IV diagnosis
  • no first-degree relative with history of psychotic, mood, or anxiety disorder

Inclusion criteria for PTSD subjects

  • current Post-Traumatic Stress Disorder, as determined by the Structured Clinical Interview for DSM-IV-Text Revision (TR) (SCID) patient research edition
  • Clinician Administered PTSD Scale for DSM-IV-TR (CAPS) score of 50 or higher

Inclusion criteria for trauma control subjects

-history of trauma (meeting the criterion A of PTSD but not a full diagnosis of PTSD)

Exclusion Criteria:

  • Current or past significant medical, neurological, or metabolic disorder or loss of consciousness for 5 minutes or more
  • active, significant suicidal ideation
  • implanted metallic devices or any Magnetic Resonance (MR) contraindications
  • women who are pregnant or breastfeeding
  • met DSM-IV criteria for alcohol/illicit substance dependence in their life-time or met alcohol/illicit substance abuse within past year
  • history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year
  • blood donation within eight weeks of the start of the study
  • radiation exposure at work that precludes study participation
  • blood pressure >140/80
  Contacts and Locations
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): NCT01691092


Locations
United States, Connecticut
Connecticut Mental Health Center
New Haven, Connecticut, United States, 06519
Yale University Magnetic Resonance Research Center (MRRC)
New Haven, Connecticut, United States, 06519
Yale University PET Center
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Irina Esterlis, PhD Yale University
  More Information

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01691092     History of Changes
Other Study ID Numbers: 1111009365
First Submitted: September 19, 2012
First Posted: September 24, 2012
Results First Submitted: December 21, 2016
Results First Posted: April 21, 2017
Last Update Posted: April 21, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Yale University:
Depression
Ketamine
PET
PTSD

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Trauma and Stressor Related Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action