PET Imaging of mGLuR5 With Drug Challenge

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Yale University
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01691092
First received: September 19, 2012
Last updated: July 29, 2015
Last verified: July 2015
  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 fMRI scans, and up to three 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: Open Label
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 PET imaging [ Time Frame: 1st scan: 90 minute baseline scan; 2nd scan: 90 minutes, ketamine administration at start of scan ] [ Designated as safety issue: No ]
    PET imaging obtained in healthy and MDD subjects. Glutamate levels determined by radiotracer uptake in PET images.


Estimated Enrollment: 100
Study Start Date: June 2012
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: September 2015 (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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18-65 years old
  • English speaking
  • No other 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 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-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 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
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: NCT01691092

Contacts
Contact: Nicole F DellaGioia, MA (203)737-6884 nicole.dellagioia@yale.edu

Locations
United States, Connecticut
Connecticut Mental Health Center Recruiting
New Haven, Connecticut, United States, 06519
Contact: Nicole DellaGioia, MA    203-737-6884    nicole.dellagioia@yale.edu   
Yale University Magnetic Resonance Research Center (MRRC) Recruiting
New Haven, Connecticut, United States, 06519
Yale University PET Center Recruiting
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Irina Esterlis, PhD Yale University
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01691092     History of Changes
Other Study ID Numbers: 1111009365
Study First Received: September 19, 2012
Last Updated: July 29, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Depression
Ketamine
PET
PTSD

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Behavioral Symptoms
Mental Disorders
Mood Disorders
Ketamine
Analgesics
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015