Imaging SV2A in Mood Disorders
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|ClinicalTrials.gov Identifier: NCT02734602|
Recruitment Status : Recruiting
First Posted : April 12, 2016
Last Update Posted : March 15, 2018
This study is designed to examine SV2A density in MDD and PTSD as a correlate of synaptic density, and to determine whether ketamine administration will reverse the synaptic loss in vivo in human subjects. To our knowledge, this is the first human study to examine SV2A in vivo in MDD and PTSD and to use the first known drug (ketamine) that rapidly reverses synaptic loss to determine whether ketamine administration could restore some of the structural changes associated with depression and PTSD.
After a screening process to determine eligibility, all subjects will participate in an MRI, and 2-3 PET scans with the administration of ketamine for one of the scans. Cognitive testing and a stress test may also be done on scan days.
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder Post-Traumatic Stress Disorder||Drug: Ketamine Behavioral: Cognitive Testing Radiation: PET Device: MRI||Not Applicable|
The goal of the study is to determine whether there are alterations in synaptic vesicle glycoprotein 2A (SV2A), a protein expressed ubiquitously in synaptic vesicles, in depression and anxiety and whether ketamine, an N-Methyl-D-aspartate (NMDA) antagonist, normalizes SV2A density at time of its greatest anti-depressant response. This study will conduct an examination of SV2A and associated consequences using neuroreceptor imaging and behavioral techniques for the following aims.
Aim 1: To compare SV2A availability in individuals with MDD, healthy control individuals, and individuals with PTSD using APP311 and PET.
Hypothesis 1: This study hypothesizes lower SV2A density in MDD and PTSD in the prefrontal cortex.
Aim 2: To determine whether ketamine administration alters SV2A density in HC, MDD, and PTSD individuals.
Hypothesis 2: This study hypothesizes administration of ketamine will lead to a significant increase in SV2A density in all subject groups (HC, MDD, and PTSD), and this increase will correlate with antidepressant response in individuals with MDD.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Imaging SV2A in Mood Disorders|
|Study Start Date :||April 2016|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||March 2021|
Subjects will take part in verbal assessments as well as computer testing.
Behavioral: Cognitive Testing
Verbal and computer assessments will be given.
Active Comparator: Magnetic Resonance Imaging
Anatomical MRIs will be performed on a Siemens 3T Trio at Yale. We will acquire the following: structural MRI, resting state MRI, diffusion tensor imaging data (DTI), and arterial spin labeling (ASL). We may also ask subjects to complete an emotional capture task.
Anatomical MRIs will be performed on a Siemens 3T Trio at Yale.
Other Name: Magnetic Resonance Imaging
Active Comparator: Positron Emission Tomography
Subjects will participate in 2-3 PET scans (up to 4 if cancelations occur) on the High Resolution Research Tomograph (HRRT), the highest resolution human brain scanner available, or the HR+ will be used to image subjects. Vital signs (blood pressure and pulse) will be obtained before and after radiotracer administration. Venous catheter(s) will be used for IV administration of the radiotracer and for venous blood sampling. An arterial catheter will be inserted by an experienced physician before the PET scan. After a baseline scan, subjects will be administered a low dose of ketamine for the second scan.
Ketamine will be administered after the initial PET scan.
Other Name: Ket
PET scan will involve infusion of a radiotracer.
Other Name: Positron Emission Tomography
- Evidence of synaptic changes in psychiatric disorders confirmed by PET data. [ Time Frame: Through study completion date, an average of 5 years. ]
- Evidence of synaptic density at time of its greatest anti-depressant response in psychiatric disorders confirmed with PET data. [ Time Frame: Through study completion date, an average of 5 years. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734602
|Contact: Sarah O, MA||203-737-7066|
|Contact: Nicole D||203-737-6884|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06519|
|Contact: Sarah O, MA 203-737-7066|
|Principal Investigator: Irina Esterlis, PhD|
|Principal Investigator:||Irina Esterlis, PhD||Yale School of Medicine|