PET Imaging of mGLuR5 With Drug Challenge

NCT01691092 | Completed Results

• 1 other identifier: 1111009365
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

Depression; Ketamine; PET; PTSD

Outcome Measures

Primary Outcomes (1)

• Change in Glutamate Levels at Baseline and After Ketamine Administration as Confirmed by Positron Emission Tomography (PET) Imaging

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

  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

Study Arms (1)

Ketamine

EXPERIMENTAL

All subjects will receive ketamine

Drug: Ketamine

Interventions

Ketamine DRUG

All subjects will receive ketamine to induce glutamate release in the brain

Also known as: ketamine IV

Ketamine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• English speaking
• No other Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnosis present, besides required as below.
• 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
• no current, or history of, any DSM-IV diagnosis
• no first-degree relative with history of psychotic, mood, or anxiety disorder
• 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
• history of trauma (meeting the criterion A of PTSD but not a full diagnosis of PTSD)

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (3)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

Yale University Magnetic Resonance Research Center (MRRC)

New Haven, Connecticut, 06519, United States

Location

Yale University PET Center

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Stress Disorders, Post-Traumatic; Depression

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Study lacks placebo control group Hemodynamic effects of ketamine may alter tracer delivery and washout Study lacks long-term follow up Only non-smokers studied Ketamine dose administered is higher than typical dose used for clinical purposes

Results Point of Contact

• Title: Irina Esterlis, Ph.D.
• Organization: Yale University - Psychiatry Department

irina.esterlis@yale.edu

(203)737-6820

Study Officials

• Irina Esterlis, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2012
• First Posted: September 24, 2012
• Study Start: June 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: April 21, 2017
• Results First Posted: April 21, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)