Examining SV2A in Mood Disorders with Ketamine

Imaging SV2A in Mood Disorders

This study is testing if ketamine can help improve brain connections in people with major depression and PTSD by looking at a specific protein in their brains.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Yale University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT02734602 on ClinicalTrials.gov

What this trial studies

This study investigates the density of SV2A, a protein linked to synaptic density, in individuals with Major Depressive Disorder (MDD) and Post-Traumatic Stress Disorder (PTSD). It aims to determine if ketamine can reverse synaptic loss by comparing SV2A levels in MDD, PTSD, healthy controls, and bipolar individuals using PET scans. Participants will undergo MRI and PET scans, cognitive testing, and a stress test, with a focus on how ketamine administration affects SV2A density and correlates with antidepressant responses.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-70 with a diagnosis of MDD or PTSD, as well as healthy controls and individuals with bipolar disorder.

Not a fit: Patients with other DSM-5 diagnoses or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new insights into the biological mechanisms of mood disorders and improve treatment strategies using ketamine.

How similar studies have performed: This approach is novel as it is the first human study to examine SV2A in vivo in MDD and PTSD and to assess the effects of ketamine on synaptic density.

Eligibility 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.

Inclusion criteria for bipolar subjects:

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

Inclusion criteria for subjects undergoing ketamine treatment

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.

Where this trial is running

New Haven, Connecticut

• PET Center — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Irina Esterlis, PhD — Yale University
• Study coordinator: Sarah B, MA

Conditions Major Depressive Disorder; Post-Traumatic Stress Disorder; depression; post-traumatic stress disorder; sv2a; ketamine; PET