Imaging Neural Correlates of Antidepressant Action of Ketamine Stereoisomers Using Pharmacological PET/MR Imaging and Metabolite Analysis.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Change in cerebral blood flow (CBF)
研究概览
简要总结
The purpose of this randomized, placebo-controlled study is to investigate pharmacodynamic differences between racemic ketamine and esketamine using functional fluorodeoxyglucose ([18F]FDG) positron emission tomography/magnetic resonance imaging (PET/MR)
Pilot study I:
A pilot study with healthy controls will be performed in order to investigate pharmacokinetic behavior and acute behavioral effects of intravenous ketamine infusion.
Pilot study II:
A pilot study including 15 healthy volunteers will be performed in order to optimize scanning procedures. The pilot study follows a randomized, placebo-controlled, double-blind, cross-over study design. After enrollment into the study all subjects will undergo two [18F]FDG PET/CT scans in the course of which they will receive either S-ketamine or placebo during the first scan and the respective other study medication during the second scan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General health based on medical history, physical examination and structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID)
- •Age 18 to 55 years
- •Right-handedness (due to potential lateralization effects of lefthanded subjects)
- •Willingness and competence to sign the informed consent form.
排除标准
- •Current or history of psychiatric or neurological disease
- •Current medical illness requiring treatment
- •Pregnancy or current breastfeeding
- •Current or former substance abuse
- •Diagnosis of an Axis-1 psychotic disorder in a first-degree relative
- •Any contraindication for MRI (e.g., MR incompatible implants, etc.) including dental implants causing signal artifacts
- •For subjects participating in earlier studies using ionizing radiation, the total radiation exposure of 30 millisievert (mSv) over the last 10 years must not be exceeded, as specified in the Austrian legislation on radiation protection (www.ris.bka.gv.at). Accordingly, body weight >100kg is an exclusion criterion (5.1 Megabequerel (MBq)/kg * 100kg * 0.019 mSv/MBq* 0.885 = 8.58 mSv per scan, the factor 0.885 is considered due to continuous radioligand infusion, see PET scanning).
- •Failure to comply with the study protocol or to follow the instruction of the investigating team.
研究组 & 干预措施
Esketamine ((S)-Ketamine)
Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms.
In a cross-over study design, esketamine will be administered during the second scan and racemic ketamine during the third scan.
干预措施: Ketamine Hydrochloride (Drug)
Esketamine ((S)-Ketamine)
Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms.
In a cross-over study design, esketamine will be administered during the second scan and racemic ketamine during the third scan.
干预措施: Esketamine (Drug)
Esketamine ((S)-Ketamine)
Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms.
In a cross-over study design, esketamine will be administered during the second scan and racemic ketamine during the third scan.
干预措施: Placebo (Drug)
Racemic ketamine ((R,S)-Ketamine)
Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms.
In a cross-over study design, racemic ketamine will be administered during the second scan and esketamine during the third scan.
干预措施: Ketamine Hydrochloride (Drug)
Racemic ketamine ((R,S)-Ketamine)
Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms.
In a cross-over study design, racemic ketamine will be administered during the second scan and esketamine during the third scan.
干预措施: Esketamine (Drug)
Racemic ketamine ((R,S)-Ketamine)
Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms.
In a cross-over study design, racemic ketamine will be administered during the second scan and esketamine during the third scan.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in cerebral blood flow (CBF)
时间窗: during PETMR/during 45 minutes of infusion
Change in CMRGlu between each PET/MR scan
Change in Cerebral metabolic rate of glucose (CMRGlu)
时间窗: during PETMR/during 45 minutes of infusion
Change in CMRGlu between each PET/MR scan
次要结局
- Change in Positive and Negative Syndrome Scale(one hour after infusion to baseline)
- Change in Brief Psychiatric Rating Scale(one hour after infusion to baseline)
- Change in Clinician Administered Dissociative States Scale(one hour after infusion to baseline)
研究者
Rupert Lanzenberger
Prof.
Medical University of Vienna