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Imaging SV2A in Mood Disorders

Primary Purpose

Major Depressive Disorder, Post-Traumatic Stress Disorder

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ketamine
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Major Depressive Disorder focused on measuring depression, post-traumatic stress disorder, sv2a, ketamine, PET

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • General inclusion criteria:

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

Inclusion criteria for depressed subjects:

  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.

Inclusion criteria for healthy controls:

1. No current, or history of any DSM-5 diagnosis.

Inclusion criteria for PTSD subjects:

1. Current Post Traumatic Stress Disorder.

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. Current psychosis, active suicidal or homicidal ideation.
  8. Positive urine toxicology screen (except for marijuana).
  9. Contraindications to PET (e.g., past or current diagnosis of cancer, poor venous access for placement of venous lines).
  10. 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.
  11. Previous or anticipated radiation exposure at work within one year of the proposed research PET scans that precludes study participation.
  12. Blood pressure >130/80 (for Aim 2, ketamine challenge); blood pressure >140/90 (non-ketamine groups).
  13. History of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).
  14. Blood donation within eight weeks of the start of the study.
  15. Current diagnosis of MDD or PTSD with psychotic features.
  16. Hematocrit levels below 35 mg/dl, and/or hemoglobin levels below 10 mg/dl.
  17. 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.

Sites / Locations

  • PET CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Active Comparator

No Intervention

Arm Label

Single PET scan

PET scans and ketamine administration

PET scans for subjects undergoing ketamine treatment

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Evidence of synaptic changes in psychiatric disorders confirmed by PET data.
Evidence of synaptic density at time of its greatest anti-depressant response in psychiatric disorders confirmed with PET data.

Secondary Outcome Measures

Full Information

First Posted
March 17, 2016
Last Updated
February 7, 2023
Sponsor
Yale University
Collaborators
VA Office of Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT02734602
Brief Title
Imaging SV2A in Mood Disorders
Official Title
Imaging SV2A in Mood Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2016 (undefined)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
Collaborators
VA Office of Research and Development

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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 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. Note: this arm is completed. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Post-Traumatic Stress Disorder
Keywords
depression, post-traumatic stress disorder, sv2a, ketamine, PET

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single PET scan
Arm Type
No Intervention
Arm Description
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.
Arm Title
PET scans and ketamine administration
Arm Type
Active Comparator
Arm Description
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.
Arm Title
PET scans for subjects undergoing ketamine treatment
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Ket
Intervention Description
Ketamine will be administered after the initial PET scan for subjects participating in the ketamine aim.
Primary Outcome Measure Information:
Title
Evidence of synaptic changes in psychiatric disorders confirmed by PET data.
Time Frame
Through study completion date, an average of 5 years.
Title
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: General inclusion criteria: Subjects will be 18-70 years old, English speaking, No other DSM-5 diagnosis present, besides required as below. Inclusion criteria for depressed subjects: 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. Inclusion criteria for healthy controls: 1. No current, or history of any DSM-5 diagnosis. Inclusion criteria for PTSD subjects: 1. Current Post Traumatic Stress Disorder. Inclusion criteria for bipolar subjects: 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. Exclusion Criteria: 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). History of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto). 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah O, MA
Phone
203-737-7066
First Name & Middle Initial & Last Name or Official Title & Degree
Nicole D
Phone
203-737-6884
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irina Esterlis, PhD
Organizational Affiliation
Yale School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
PET Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah O, MA
Phone
203-737-7066
First Name & Middle Initial & Last Name & Degree
Irina Esterlis, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Imaging SV2A in Mood Disorders

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