Imaging SV2A in Mood Disorders
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Evidence of synaptic changes in psychiatric disorders confirmed by PET data.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
- •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).
- •Arterial line exclusion: History of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).
- •Arterial line exclusion: 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.
研究组 & 干预措施
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.
干预措施: Ketamine (Drug)
结局指标
主要结局
Evidence of synaptic changes in psychiatric disorders confirmed by PET data.
时间窗: 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.
时间窗: Through study completion date, an average of 5 years.
次要结局
未报告次要终点
研究者
Irina Esterlis
Assistant Professor
Yale University