Imaging SV2A in Mood Disorders

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-30

Study Completion Date

2027-03-31

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Major Depressive Disorder Post-Traumatic Stress Disorder

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Single PET scan

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

PET scans and ketamine administration

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.

Group Type ACTIVE_COMPARATOR

Ketamine

Intervention Type DRUG

Ketamine will be administered after the initial PET scan for subjects participating in the ketamine aim.

PET scans for subjects undergoing ketamine treatment

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Ketamine

Ketamine will be administered after the initial PET scan for subjects participating in the ketamine aim.

Intervention Type DRUG

Other Intervention Names

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Ket

Eligibility Criteria

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Inclusion Criteria

1. Subjects will be 18-70 years old,
2. English speaking,
3. No other DSM-5 diagnosis present, besides required as below.

1. Meet DSM-5 diagnostic criteria for Major Depressive Disorder, and for a current depressive episode.
2. 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.

1\. Meet DSM-5 diagnostic criteria for bipolar disorder.

1. 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).
2. Undergoing ketamine treatment.

Exclusion Criteria

1. History of significant medical illness that would contraindicate study participation based on above criteria and PI/MD history review.
2. 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.
3. Full scale IQ lower than 70.
4. 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.
5. Pregnancy or breast-feeding.
6. 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.
7. Claustrophobia.
8. Current psychosis, active suicidal or homicidal ideation.
9. Positive urine toxicology screen (except for marijuana).
10. Contraindications to PET (e.g., past or current diagnosis of cancer, poor venous access for placement of venous lines).
11. 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.
12. Previous or anticipated radiation exposure at work within one year of the proposed research PET scans that precludes study participation.
13. Blood pressure \>130/80 (for Aim 2, ketamine challenge); blood pressure \>140/90 (non-ketamine groups).
14. Arterial line exclusion: History of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).
15. Arterial line exclusion: Blood donation within eight weeks of the start of the study.
16. Current diagnosis of MDD or PTSD with psychotic features.
17. Hematocrit levels below 35 mg/dl, and/or hemoglobin levels below 10 mg/dl.
18. 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.

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes