PET Imaging of mGLuR5 With Drug Challenge

Yale University

Status

Completed

Conditions

Post-Traumatic Stress Disorder (PTSD)

Major Depressive Disorder

Treatments

Drug: Ketamine

Study type

Interventional

Funder types

Other

Identifiers

NCT01691092

1111009365

Details and patient eligibility

About

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.

Full 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.

Enrollment

79 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts 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