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PET Imaging of mGLuR5 With Drug Challenge

Primary Purpose

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

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Ketamine

About this trial

This is an interventional other trial for Major Depressive Disorder focused on measuring Depression, Ketamine, PET, PTSD

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Connecticut Mental Health Center
Yale University Magnetic Resonance Research Center (MRRC)
Yale University PET Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketamine

Arm Description

All subjects will receive ketamine

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01691092

First Posted

September 19, 2012

Last Updated

March 10, 2017

Sponsor

Yale University

1. Study Identification

Unique Protocol Identification Number

NCT01691092

Brief Title

PET Imaging of mGLuR5 With Drug Challenge

Official Title

PET Imaging of mGluR5 With Drug Challenge

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

June 2012 (undefined)

Primary Completion Date

February 2016 (Actual)

Study Completion Date

February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Depression, Ketamine, PET, PTSD

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

79 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ketamine

Arm Type

Experimental

Arm Description

All subjects will receive ketamine

Intervention Type

Drug

Intervention Name(s)

Ketamine

Other Intervention Name(s)

ketamine IV

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Irina Esterlis, PhD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Connecticut Mental Health Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

Facility Name

Yale University Magnetic Resonance Research Center (MRRC)

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

Facility Name

Yale University PET Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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PET Imaging of mGLuR5 With Drug Challenge

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