Major Depressive DisorderNCT02734602
Imaging SV2A in Mood Disorders
A study testing Ketamine in people with Major Depressive Disorder and Post-Traumatic Stress Disorder, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Post-Traumatic Stress Disorder
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General inclusion criteria:
- 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.
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- 1. No current, or history of any DSM-5 diagnosis.
- 1. Current Post Traumatic Stress Disorder.
- 1. Meet DSM-5 diagnostic criteria for bipolar disorder.
- Inclusion criteria for subjects undergoing ketamine treatment
- 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.
Who cannot join
- 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.
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- 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).
- Arterial line exclusion: History of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).
- Arterial line exclusion: Blood donation within eight weeks of the start of the study.
- Current diagnosis of MDD or PTSD with psychotic features.
- Hematocrit levels below 35 mg/dl, and/or hemoglobin levels below 10 mg/dl.
- Weight under 110 lbs for subjects who will participate in portions of this study for which the blood draw is at or above a typical blood donation.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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, bipolar individuals, and individuals with PTSD using APP311 or SDM-8 (aka SynVesT-1) and PET.
Hypothesis 1: This study hypothesizes lower SV2A density in MDD, BD, 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.
Aim 3: To determine the extent of SV2A density changes after prolonged treatment with ketamine in individuals with depression (n=10).
Hypothesis 3: We hypothesize ketamine treatment will increase SV2A density in these individuals. These are individuals who are undergoing ketamine treatment at Yale, CMHC, or surrounding clinics.
Aim 4: To examine changes in SV2A associated with gender within each psychiatric group.
- Being tested
- Ketamine
- Keywords
- depression, post-traumatic stress disorder, sv2a, ketamine, PET
- Medical subject headings
- Depressive Disorder, Major, Stress Disorders, Post-Traumatic, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ket
Ketamine will be administered after the initial PET scan for subjects participating in the ketamine aim.
| Study group | Role | What they receive |
|---|---|---|
| Single PET scan | No intervention | Subjects 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 comparator | 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.
Bipolar subjects will not participate in any ketamine arms. Receives: Drug: Ketamine |
| PET scans for subjects undergoing ketamine treatment | No intervention | For 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of synaptic changes in psychiatric disorders confirmed by PET data.
Measured: 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.
Measured: Through study completion date, an average of 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study startApr 2016
- Primary completionJan 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Office of Research and Development
- Responsible party
- Principal investigator, Irina Esterlis, Yale University
- Investigators
- Irina Esterlis, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02734602
- Sponsor's protocol ID
- 1511016789
- Status last verified
- Jun 2026
- First submitted
- 17 Mar 2016
- Last updated
- 8 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging SV2A in Mood Disorders
- ClinicalTrials.gov ID
- NCT02734602
- Acronym / sponsor ID
- 1511016789
- Keywords
- depression, post-traumatic stress disorder, sv2a, ketamine, PET
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- VA Office of Research and Development
- Study start
- Apr 2016
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 12 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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, bipolar individuals, and individuals with PTSD using APP311 or SDM-8 (aka SynVesT-1) and PET.
Hypothesis 1: This study hypothesizes lower SV2A density in MDD, BD, 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.
Aim 3: To determine the extent of SV2A density changes after prolonged treatment with ketamine in individuals with depression (n=10).
Hypothesis 3: We hypothesize ketamine treatment will increase SV2A density in these individuals. These are individuals who are undergoing ketamine treatment at Yale, CMHC, or surrounding clinics.
Aim 4: To examine changes in SV2A associated with gender within each psychiatric group.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Single PET scan | No intervention | –Subjects 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 comparator | Drug: KetamineSubjects 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 intervention | –For 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- General inclusion criteria:
- 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.
- 1. No current, or history of any DSM-5 diagnosis.
- 1. Current Post Traumatic Stress Disorder.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: KetKetamine will be administered after the initial PET scan for subjects participating in the ketamine aim. | Drug | PET scans and ketamine administration |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Irina Esterlis, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketamine in people with Major Depressive Disorder and Post-Traumatic Stress Disorder, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evidence of synaptic changes in psychiatric disorders confirmed by PET data. (time frame: Through study completion date, an average of 5 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2026.