Biomarker Study of Acamprosate in Schizophrenia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 4
- 主要终点
- Anterior Cingulate Cortex - N-acetylaspartate
研究概览
简要总结
NMDA receptors are brain receptors that are stimulated by glutamate. Poorly functioning NMDA receptors are thought to be involved in the pathology of schizophrenia. This hypothesis is based on the observation that PCP, which blocks the NMDA receptor, produces symptoms and cognitive impairments similar to schizophrenia. Efforts to enhance the function of the NMDA receptor with glycine and D-cycloserine have met with limited success. An alternative approach would be to use the drug acamprosate.
Acamprosate, FDA-approved for maintenance of sobriety after detoxification from alcohol, seems to act through modulation of the NMDA receptor. In the lab, acamprosate has been noted to act as an antagonist when the NMDA receptors are maximally stimulated but as an agonist when NMDA receptor stimulation is minimal. This "smart drug" action makes acamprosate appealing for use in schizophrenia. If acamprosate works as a smart drug in patients, then we would predict that it would enhance the function of NMDA receptors in schizophrenia and improve cognition and the symptoms of the illness. Additionally, acamprosate seems to modulate the NMDA receptor in novel ways distinct from glycine and D-cycloserine.
We will also see if the response to acamprosate differs based on whether participants do or do not have a past history of alcohol use disorders.
详细描述
We propose to measure the response of symptoms and cognition in people schizophrenia given acamprosate or placebo. We hypothesize that symptoms and cognition will improve following two weeks of acamprosate. We will also use proton magnetic resonance spectroscopy (MRS) to examine the effect of acamprosate on glutamate & glutamine (Glu&Gln) brain levels in people with schizophrenia. We hypothesize that Glu&Gln concentrations in people with chronic schizophrenia will increase following two weeks of treatment with acamprosate.
The proposed study will consist of 50 individuals with chronic schizophrenia/schizoaffective disorder, 18-55 years old, from in/outpatient programs at the Maryland Psychiatric Research Center (MPRC). The dose of acamprosate will follow manufacturer recommendations with two 333mg tablets given three times per day. MRS will be acquired from areas involved in schizophrenia [dorsolateral-prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC)] at baseline and week two. Symptom ratings and cognitive testing will occur at baseline and be repeated at week two.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DSM-IV diagnosis of schizophrenia/schizoaffective disorder
- •Age 18-55 years
- •Male or female
- •Any Race/ethnicity
- •Participants will be analyzed separately depending on whether they do or do not have a history of an alcohol use disorder
排除标准
- •Pregnant/nursing females or females not using adequate birth control
- •Documented history of mental retardation/severe neurological disorder/head injury with loss of consciousness
- •DSM-IV diagnosis of substance dependence in previous six months/abuse in the previous three months (except nicotine)
- •Serious suicidal risk in the previous six months
- •History of renal failure/creatinine clearance of less than 50mL/min
- •Current treatment with clozapine
- •Contraindication to MRI scanning.
研究组 & 干预措施
Single Arm
All subjects will have baseline measures, receive acamprosate for 2 weeks, then have measures repeated.
干预措施: Acamprosate (Drug)
结局指标
主要结局
Anterior Cingulate Cortex - N-acetylaspartate
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Right Dorsal Lateral Prefrontal Cortex - Glutamate
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Anterior Cingulate Cortex - Creatinine
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Right Dorsal Lateral Prefrontal Cortex - Creatinine
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Right Dorsal Lateral Prefrontal Cortex - N-acetylaspartate
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Left Dorsal Lateral Prefrontal Cortex - Creatinine
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Creatinine brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Left Dorsal Lateral Prefrontal Cortex - Glutamate
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Anterior Cingulate Cortex - Myo-inositol
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Right Dorsal Lateral Prefrontal Cortex - Choline
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Left Dorsal Lateral Prefrontal Cortex - Choline
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Anterior Cingulate Cortex - Glutamate
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Glutamate brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Anterior Cingulate Cortex - Choline
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Choline brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Anterior Cingulate Cortex (ACC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Right Dorsal Lateral Prefrontal Cortex - Myo-inositol
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Right Dorsal Lateral Prefrontal Cortex (R DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Left Dorsal Lateral Prefrontal Cortex - N-acetylaspartate
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
N-acetylaspartate (NAA) brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Left Dorsal Lateral Prefrontal Cortex - Myo-inositol
时间窗: Baseline screening (Scan 1) and again after 2 weeks of Acamprosate treatment (Scan 2)
Myo-inositol brain metabolite levels between those with and without a lifetime history of prior alcohol abuse/dependence in the Left Dorsal Lateral Prefrontal Cortex (L DLPFC) using Magnetic Resonance Spectroscopy (MRS). Metabolite concentration was calculated from the MRS signals and reported in "mM".
Fractional Anisotropy Measured With Diffusion Tensor Imaging
时间窗: Completion of two scans
Diffusion Tensor Imaging Frational Anisotropy (FA) Measures by Lifetime History of Alcohol Abuse/Dependence and Brain Hemisphere.
次要结局
- BPRS - Symptoms of Psychosis Total Score(Baseline (Treatment Week 0) and End of Study (Treatment Week 2))
- SANS - Negative Symptoms of Schizophrenia Total Score(Baseline (Treatment Week 0) and End of Study (Treatment Week 2))
- BPRS - Symptoms of Psychosis Change in Scores(Baseline (Treatment Week 0) and End of Study (Treatment Week 2))
- Cognitive Impairment(Change from Baseline (Treatment Week 0) to End of Study (Treatment Week 2))
研究者
Robert Buchanan
Chief, Maryland Psychiatric Research Center, Outpatient Research Program
University of Maryland, Baltimore