PET Imaging of mGLuR5 With Drug Challenge

Major Depressive Disorder Clinical Trial

Official title:

PET Imaging of mGluR5 With Drug Challenge

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01691092
• Other study ID #: 1111009365
• Status: Completed
• Phase: N/A
• First received: September 19, 2012
• Last updated: May 11, 2016
• Start date: June 2012
• Est. completion date: February 2016

Study information

• Verified date: May 2016
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder
• Post-Traumatic Stress Disorder (PTSD)
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Drug:
• Ketamine
All subjects will receive ketamine to induce glutamate release in the brain

Locations

Country	Name	City	State
United States	Connecticut Mental Health Center	New Haven	Connecticut
United States	Yale University Magnetic Resonance Research Center (MRRC)	New Haven	Connecticut
United States	Yale University PET Center	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glutamate levels at baseline and after ketamine administration as confirmed by PET imaging	PET imaging obtained in healthy and 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	No