Neural Mechanisms of Anticholinergic Burden in Mid- to Late-Life Schizophrenia Spectrum
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- Change in cognitive performance
研究概览
简要总结
In this study, the investigators will examine whether a deprescription of unnecessary anticholinergic drugs (benztropine or trihexyphenidyl) can augment quality of life, functioning, and neurocognition in individuals who with schizophrenia. Individuals identified by clinical services who have unneeded prescriptions benztropine or trihexyphenidyl will be eligible for deprescription and study entry. Following a baseline evaluation and magnetic resonance imaging (MRI), participants will will be randomized to either staying on their anticholinergic drugs or undergoing deprescription per routine clinical care, and will undergo follow-up evaluations across 6 months. The investigators predict that reducing and deprescribing these drug, if clinically determined to be unnecessary will will enhance functioning, neurocognition
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
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Primary DSM-defined diagnosis of schizophrenia, schizoaffective disorder, or unspecified psychotic disorder, verified by the Structured Clinical Interview for DSM-5 (SCID).
- •Prescription of benztropine or trihexyphenidyl for at least 6 months
- •Age 35-70 years.
- •ACBS score >=
- •Mild or absent extrapyramidal symptoms (Determined by clinical pharmacists and prescribers).
- •Competency and willingness to sign informed consent.
- •Inclusion criteria for the healthy control group:
- •Age 40-70 years.
- •Competency and willingness to sign informed consent.
排除标准
- •Serious anticholinergic side-effects (e.g., fever, blurred vision) indicative of a need for immediate removal of anticholinergics,
- •Serious neurologic or medical condition/treatment that impacts the brain and Neurodegenerative conditions such as Parkinson's, dementia, etc.; autoimmune conditions such as Multiple Sclerosis (MS) and lupus; as well as traumatic brain injury (TBI).
- •Significant risk of suicidal or homicidal behavior.
- •Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent.
- •Contraindications for MR imaging (e.g., a pacemaker).
- •Current SCID-verified substance use disorder will be excluded to avoid the confounding impact of significant substance use comorbidity. Participants with a history of substance use disorder that is in early or full remission will be eligible, to enhance generalizability.
- •Patients concurrently treated with electroconvulsive therapy will be excluded because of its effects on cognition.
- •Exclusion criteria for Healthy Control (HC) subjects:
- •No history of psychotic illness and no active Axis I disorder as determined by clinical interview using the SCID-NP.
- •Score greater than 1 on the ACB scale.
- •MR imaging contraindications.
- •Neurologic conditions, any serious non-psychiatric disorder that could affect brain functioning, or intellectual disability.
- •HC with family history of psychosis will be excluded, as such individuals show subtle, but significant cognitive and neurobiological abnormalities.
- •Individuals currently taking anticholinergic medications for reasons other than SSD.
研究组 & 干预措施
Healthy Controls
In this arm, a healthy control group with minimal anticholinergic burden will be examined longitudinally.
No Anticholinergic Deprescription
In this arm, no deprescription of benztropine or trihexyphenidyl will occur.
干预措施: No Anticholinergic Deprescription (Drug)
Anticholinergic Deprescription
In this arm, clinically determined unneeded benztropine or trihexyphenidyl will be deprescribed, per routine care by clinical providers.
干预措施: Anticholinergic Deprescription (Drug)
结局指标
主要结局
Change in cognitive performance
时间窗: 6 months
We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in cognitive performance via scores from the MATRICS Consensus Cognitive Battery.
Change in scores on quality of life assessments.
时间窗: 6 months
We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in quality of life, measured with the WHOQOL-BREF.
Change in scores on functional outcome assessments.
时间窗: 6 months
We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in functional outcomes, measured with the Specific Level of Functioning Scale.
change in activation of neurocognitive networks
时间窗: 6 months
We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in brain activation of the cognitive control network via the AX-CPT, and activation of the hippocampus during memory encoding/retrieval via the Relational and Item-Specific Encoding task.
change in brain functional connectivity.
时间窗: 6 months
We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in brain functional connectivity between the basal forebrain and linked structures, such as regions of the cognitive control network, and the globus pallidus.
Brain glutamate concentration
时间窗: 6 months
We will examine whether the anticholinergic deprescription group, relative to the non-deprescription group, shows an increase in brain glutamate concentrations in the hippocampus and the dorsal anterior cingulate cortex.
次要结局
未报告次要终点
研究者
Deepak K. Sarpal, M.D.
Associate Professor
University of Pittsburgh