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Imaging SV2A in Mood Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02734602
Recruitment Status : Recruiting
First Posted : April 12, 2016
Last Update Posted : February 10, 2020
Sponsor:
Collaborator:
VA Office of Research and Development
Information provided by (Responsible Party):
Irina Esterlis, Yale University

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.


Condition or disease Intervention/treatment Phase
Major Depressive Disorder Post-Traumatic Stress Disorder Drug: Ketamine Behavioral: Cognitive Testing Radiation: PET Device: MRI Not Applicable

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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Imaging SV2A in Mood Disorders
Study Start Date : April 2016
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Cognitive Testing
Subjects will take part in verbal assessments as well as computer testing.
Behavioral: Cognitive Testing
Verbal and computer assessments will be given.

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.
Device: MRI
Anatomical MRIs will be performed on a Siemens 3T Trio at Yale.
Other Name: Magnetic Resonance Imaging

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.
Drug: Ketamine
Ketamine will be administered after the initial PET scan.
Other Name: Ket

Radiation: PET
PET scan will involve infusion of a radiotracer.
Other Name: Positron Emission Tomography




Primary Outcome Measures :
  1. Evidence of synaptic changes in psychiatric disorders confirmed by PET data. [ Time Frame: Through study completion date, an average of 5 years. ]
  2. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734602


Contacts
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Contact: Sarah O, MA 203-737-7066
Contact: Nicole D 203-737-6884

Locations
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United States, Connecticut
PET Center Recruiting
New Haven, Connecticut, United States, 06519
Contact: Sarah O, MA    203-737-7066      
Principal Investigator: Irina Esterlis, PhD         
Sponsors and Collaborators
Yale University
VA Office of Research and Development
Investigators
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Principal Investigator: Irina Esterlis, PhD Yale School of Medicine

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Responsible Party: Irina Esterlis, Assistant Professor, Yale University
ClinicalTrials.gov Identifier: NCT02734602    
Other Study ID Numbers: 1511016789
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: February 10, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Irina Esterlis, Yale University:
depression
post-traumatic stress disorder
sv2a
ketamine
PET
Additional relevant MeSH terms:
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Disease
Depressive Disorder
Depressive Disorder, Major
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Mood Disorders
Mental Disorders
Trauma and Stressor Related Disorders
Pathologic Processes
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action