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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 3, 2021
Sponsor:
Collaborator:
VA Office of Research and Development
Information provided by (Responsible Party):
Irina Esterlis, Yale University

Tracking Information
First Submitted Date  ICMJE March 17, 2016
First Posted Date  ICMJE April 12, 2016
Last Update Posted Date March 3, 2021
Study Start Date  ICMJE April 2016
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2016)
  • 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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Imaging SV2A in Mood Disorders
Official Title  ICMJE Imaging SV2A in Mood Disorders
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, 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. 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.

New Aim pending.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Major Depressive Disorder
  • Post-Traumatic Stress Disorder
Intervention  ICMJE
  • Drug: Ketamine
    Ketamine will be administered after the initial PET scan.
    Other Name: Ket
  • Behavioral: Cognitive Testing
    Verbal and computer assessments will be given.
  • Radiation: PET
    PET scan will involve infusion of a radiotracer.
    Other Name: Positron Emission Tomography
  • Device: MRI
    Anatomical MRIs will be performed on a Siemens 3T Trio at Yale.
    Other Name: Magnetic Resonance Imaging
Study Arms  ICMJE
  • Cognitive Testing
    Subjects will take part in verbal assessments as well as computer testing.
    Intervention: Behavioral: Cognitive Testing
  • 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.
    Intervention: Device: MRI
  • 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.
    Interventions:
    • Drug: Ketamine
    • Radiation: PET
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 5, 2016)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Sarah O, MA 203-737-7066
Contact: Nicole D 203-737-6884
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02734602
Other Study ID Numbers  ICMJE 1511016789
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Irina Esterlis, Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE VA Office of Research and Development
Investigators  ICMJE
Principal Investigator: Irina Esterlis, PhD Yale School of Medicine
PRS Account Yale University
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP