Imaging SV2A in Mood Disorders
1 other identifier
interventional
130
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable major-depressive-disorder
Started Apr 2016
Longer than P75 for not_applicable major-depressive-disorder
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 17, 2016
CompletedStudy Start
First participant enrolled
April 1, 2016
CompletedFirst Posted
Study publicly available on registry
April 12, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
April 11, 2025
April 1, 2025
10.8 years
March 17, 2016
April 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Evidence of synaptic changes in psychiatric disorders confirmed by PET data.
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.
Through study completion date, an average of 5 years.
Study Arms (3)
Single PET scan
NO INTERVENTIONSubjects will participate in 1 PET scan (up to 2 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.
PET scans and ketamine administration
ACTIVE COMPARATORSubjects 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. Bipolar subjects will not participate in any ketamine arms.
PET scans for subjects undergoing ketamine treatment
NO INTERVENTIONFor subjects currently undergoing treatment with ketamine. Subjects will participate in 1-3 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. Baseline scan will occur prior to initiation of ketamine treatment. Subsequent scans will occur after several treatments with ketamine and after completion of treatment. Bipolar subjects will not participate in any ketamine arms.
Interventions
Ketamine will be administered after the initial PET scan for subjects participating in the ketamine aim.
Eligibility Criteria
You may qualify if:
- Subjects will be 18-70 years old,
- English speaking,
- No other DSM-5 diagnosis present, besides required as below.
- Meet DSM-5 diagnostic criteria for Major Depressive Disorder, and for a current depressive episode.
- Treatment or non-treatment seeking who understand that this study is for research purposes only.
- \. No current, or history of any DSM-5 diagnosis.
- \. Current Post Traumatic Stress Disorder.
- \. Meet DSM-5 diagnostic criteria for bipolar disorder.
- Meet DSM-5 diagnostic criteria for Major Depressive Disorder, and for a current depressive episode, as assessed by structured interview for DSM-5 diagnosis (SCID).
- Undergoing ketamine treatment.
You may not qualify if:
- History of significant medical illness that would contraindicate study participation based on above criteria and PI/MD history review.
- Lifetime history of neurologic abnormality including seizure disorder, cerebrovascular or neoplastic lesion, neurodegenerative disorder, or significant head trauma resulting in post-traumatic amnesia \>24 hours.
- Full scale IQ lower than 70.
- Contraindication to MRI scanning including claustrophobia and presence of a ferromagnetic object, including orthodontic braces. All participants will be screened for metal objects by the same methods used for routine clinical MRI scanning.
- Pregnancy or breast-feeding.
- Met DSM-5 criteria for mild substance use disorder (except nicotine and marijuana) within the past 6 months or met DSM-5 criteria for moderate to severe substance use disorder within the past year.
- Claustrophobia.
- Current psychosis, active suicidal or homicidal ideation.
- Positive urine toxicology screen (except for marijuana).
- Contraindications to PET (e.g., past or current diagnosis of cancer, poor venous access for placement of venous lines).
- 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.
- Previous or anticipated radiation exposure at work within one year of the proposed research PET scans that precludes study participation.
- Blood pressure \>130/80 (for Aim 2, ketamine challenge); blood pressure \>140/90 (non-ketamine groups).
- Current diagnosis of MDD or PTSD with psychotic features.
- Hematocrit levels below 35 mg/dl, and/or hemoglobin levels below 10 mg/dl.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Yale Universitylead
- VA Office of Research and Developmentcollaborator
Study Sites (1)
PET Center
New Haven, Connecticut, 06519, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Irina Esterlis, PhD
Yale University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
March 17, 2016
First Posted
April 12, 2016
Study Start
April 1, 2016
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
March 1, 2027
Last Updated
April 11, 2025
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will not share