PET Imaging of mGLuR5 With Drug Challenge

Ketamine

Brief Summary

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.

Intervention / Treatment

  • Ketamine (DRUG)
    All subjects will receive ketamine to induce glutamate release in the brain

Condition or Disease

  • Major Depressive Disorder
  • Post-Traumatic Stress Disorder (PTSD)

Phase

  • Not Applicable

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 65 Years
    Enrollment: 79 (ACTUAL)
    Funded by: Other
    Allocation: N/A
    Primary Purpose: Other

    Masking

    Clinical Trial Dates

    Start date: Jun 01, 2012
    Primary Completion: Feb 01, 2016 ACTUAL
    Completion Date: Feb 01, 2016 ACTUAL
    Study First Posted: Sep 24, 2012 ESTIMATED
    Results First Posted: Apr 21, 2017 ACTUAL
    Last Updated: Mar 10, 2017

    Sponsors / Collaborators

    Lead Sponsor: Yale University
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    New Haven, Connecticut, USA

    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.

    Participant Groups

    • All subjects will receive ketamine

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 65
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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

    Primary Outcomes

    • PET imaging obtained in healthy and Major Depressive Disorder (MDD) subjects. Glutamate levels determined by radiotracer uptake in PET images.

    More Details

    NCT Number: NCT01691092
    Other IDs: 1111009365
    Study URL: https://clinicaltrials.gov/study/NCT01691092
    Last updated: Sep 29, 2023