Biomarker Assessment of Pomaglumetad on Glutamate Targets: Proof of Clinical Mechanism of Action (POCM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 4
- 主要终点
- PharmacoBOLD change
研究概览
简要总结
The study will evaluate the effects of the mGluR2/3 partial agonist LY2140023 (Pomaglumetad Methionil, "POMA") at selected doses on ketamine-stimulated glutamate release in prefrontal cortex as measured by pharmacoBOLD fMRI (also termed resting BOLD fMRI).
详细描述
This study evaluates the effects of POMA at selected doses on ketamine-stimulated glutamate increase in the prefrontal cortex hypothesized to simulate the synaptic dysregulation that occurs endogenously in the pathogenesis of schizophrenia. The purpose of this is: 1) to determine whether the low dose (40 mg BID) utilized in recent (failed) clinical trials is sufficient to engage the primary target and 2) whether a higher (160 mg BID) dose, representing the maximum tolerated dose of POMA, engages the target to a greater degree. This study will further validate pharmacoBOLD as biomarker of mGluR2/3 target engagement, permitting its future use in other glutamatergic drug development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Medically healthy
- •Capable of understanding the study procedures and able to provide informed consent
- •Men and women must agree to use a reliable method of birth control during the study. Women who are post-menopausal or otherwise not of childbearing potential are also eligible
排除标准
- •Current or past Axis I psychiatric history
- •Positive urine toxicology
- •History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated in prior research ketamine studies will be eligible. Subjects can have infusions not more frequently than biweekly, and not more than 1/month on average, therefore subjects entering the study will need to wait one month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
- •History of first-degree relative with schizophrenia
- •History of violence
- •Presence or positive history of significant medical illness
- •Presence or positive history neurological illness or any other disease/procedure/accident/intervention association with significant injury to or malfunction of the central nervous system (CNS) or history of significant head injury
- •Pregnancy or breast feeding
- •Metal implants, pacemaker, other metal or paramagnetic objects contained within the body
- •Medicinal patch, unless removed prior to MRI scan
- •Currently taking any psychotropic medication, including antidepressant medications, benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic medications and stimulants.
- •Claustrophobia
- •Suicidal ideation with intent or plan in the 6 months prior to screening
- •Weight > 86.95 kg (191.2 lbs)
- •Subthreshold pharmacoBOLD response during screening ketamine infusion
研究组 & 干预措施
Placebo
Placebo BID for 10 days
干预措施: placebo (Drug)
POMA 40 mg BID
40 mg BID for 10 days
干预措施: POMA (Drug)
POMA 160 mg BID
160 mg BID for 10 days
干预措施: POMA (Drug)
结局指标
主要结局
PharmacoBOLD change
时间窗: Day 1 to Day 10
pharmacoBOLD change, as summarized by the Amplitude measure
次要结局
- Brief Psychiatric Rating Scale (BPRS)(Day 1 to Day 10)
- Clinician Administered Dissociative States Scale (CADSS)(Day 1 to Day 10)
研究者
Marlene Carlson
Study Manager
New York State Psychiatric Institute