Studying Human Cognition During Deep Brain Stimulation Surgery Using High-Density Neural Probes and Pharmacological Interventions

University of Texas Southwestern Medical Center1 个研究点分布在 1 个国家目标入组 30 人开始时间: 2026年10月1日最近更新: 2026年7月23日

适应症

试验速览

阶段: 1 期
状态: 尚未招募
发起方: University of Texas Southwestern Medical Center
入组人数: 30
试验地点: 1
主要终点: Cognitive control task-related changes in brain electrical activity in participants from baseline at cholinergic modulation post-intervention (approx. within 2-5 hrs)

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a research study to determine how COBENFY KarXT (FDA approved), a drug which has been approved for treatment of certain disorders, affects brain activity and cognitive tasks which may be regulated by the cholinergic system.

This study aims to answer: 1) how cholinergic circuitries act during task performance in humans, and 2) develop a better understanding of how cognitive control interacts with learning, memory and decision making in the setting of cholinergic manipulation.

Participants will complete a single treatment arm, regardless of which surgical procedure they are to receive. An anesthesiologist or other clinical staff will administer either the drug or the saline at a critical point which addresses the research questions, prior to patient surgery. This will be either with the drug, or the placebo pill. Half of the participants will be randomized to receive the drug, and the other half of these the placebo. Participants will be unaware whether the actual drug has been received.

Essential tremor patients who participate will complete a cognitive task during an awake surgery. Epilepsy patients who participate will have a resting state recording during the procedure from the deep cortical layers of the brain. A probe will be used during the surgery to measure the effects of this drug and other procedures of the study on the cholinergic system. This probe is the clinical probe known as the AlphaOmega, which is FDA approved for standard of care procedures.

Researchers will compare the brain activity between treatment arms to determine what brain activity changes based on the cholinergic manipulation.

详细描述

Consenting: Prior to conducting any research related tests / procedures, the patient will be consented. At least 24 hours before scheduled surgery (most commonly the week before surgery), prospective participants for our study are contacted by a member of the study team via phone, to inform them of their candidacy to participate in our study, explain study details and answer questions and ultimately ask about their interest in participation. Once in the operating suite, the patient will be put under anesthesia for clinical purposes for surgery.

Prepare the OR before patient arrival: Before the patient is in the room, we will have at least one research team member go to the OR to set up the NeuroOmega recording system, which is also used as standard-of-care.

Pharmaceutical Preparation and Administration: Drug administration will be prepared by the pharmacy. We will obtain the drug from the pharmacy during the pre-operative phase in a single dose of 50 mg/20 mg orally BID of xanomeline and trospium chloride (COBENFY) or placebo pill. Patients will be given the dose as part of pre-operative preparation if part of the group randomized to receive the drug by members of the study team qualified for drug administration. As patients will receive a single dose of the medication during their participation, we do not anticipate serious side effects which occur from prolonged use, nor anticipate that cholinergic mechanisms activated at the lowest dose will result in issues such as seizures or nausea. However, should the patient pass the pre-screening process and consent to participation, safety measures will be in place for monitoring patients during participation. Administration will target intraoperative peak concentration of the xanomeline component at 2 hours. Oral intake status has little impact on kinetics.

Risk mitigation for drug administration will include:

A preop checklist for possible side effects or contraindications.
Discussion with neuroanesthesia partners regarding suitability for administration.
Use of low dosages of medicines in line with previous cognitive experiments, not expected to have substantial effects on CV systems.
Assess patient for side effects from initial administration every 20 minutes. Immediate monitoring and potential to reverse effects of the medicines during surgery.
Continuous monitoring of vital signs in surgery.
Inquire at 20 minute intervals about nausea, vomiting, abdominal cramping, blurred vision, dry mouth.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Factorial
主要目的: Basic Science
盲法: Single (Participant)

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: 否

入选标准

•Study Population
•Inclusion Criteria for Essential Tremor Patients:
•Diagnosis of Essential Tremor
•Recommended to undergo deep brain stimulation implantation surgery for surgical management of medication-resistant tremor based on clinical indications

排除标准

•for Essential Tremor Patients:
•Patients with recent use (within one week) of anticoagulant or antiplatelet agent
•Contraindication to use of cholinergic modulation
•Inclusion Criteria for Epilepsy Patients
•Diagnosis of intractable epilepsy
•Undergoing neuromodulation procedure that utilizes insertion of electrodes into subcortical structures, including the thalamus or hippocampus
•Undergoing neuromodulation procedure that utilizes frame-based insertion of electrodes into the thalamus (ANT or CM)
•Exclusion Criteria for Epilepsy Patients:
•Patients with recent use (within one week) of anticoagulant or antiplatelet agent
•Contraindication to use of cholinergic modulation
•Contraindication for cholinergic modulation in both patient sets will be assessed by members of the treatment team (e.g. epileptologist), as well as a neuroanesthesiologist. Multiple medications and conditions are singular disqualifiers; however some medications are eliminated only in combination following neuroanesthesiologist evaluation. Patients at risk of reaction to the treatment arm based on concurrent or recent medications or other health conditions will be excluded from participation.
•Inclusion Criteria for Study Participation
•Is patient between 18-70?
•In general good health, aside from history of epilepsy or essential tremor, as ascertained by medical history, physical exam, clinical labs, and ECG?
•Candidate for surgery as determined independently by the patient's treating physician/clinical team as part of the patient's routine medical care?
•Able to read, understand, and provide written, dated informed consent, and participate in cognitive tasks?
•Exclusion Criteria for Study Participation
•Female that is pregnant, breastfeeding, or has a positive pregnancy test?
•Under 18, over 70, or currently a prisoner on medical release?
•Hepatic impairment (moderate or severe)?
•Renal impairment (moderate or severe)?
•Untreated narrow angle glaucoma?
•Bladder obstruction, prostatic hyperplasia (BPH), diabetic cystopathy, pre-existing urinary retention?
•History of hypersensitivity to COBENFY or trospium chloride?
•Biliary disease, including symptomatic gallstones, gallbladder disorders, pancreatitis?
•Fluoxetine, paroxetine, bupropion, terbinafine?
•Buspirone or eletriptan?
•Digoxin, colchicine, apixaban?
•Diphenhydramine, beztropine, oxybutynin?
•Benztropine, trihexyphenidyl, tolterodine, solifenacin, darifenacin, fesoterodine, hyoscyamine, dicyclomine, scopolamine?

结局指标

主要结局

Cognitive control task-related changes in brain electrical activity in participants from baseline at cholinergic modulation post-intervention (approx. within 2-5 hrs)