Human Cognition During Surgery: Stimulation-based and Cholinergic Modulation

Conditions

• Cognitive Control
• Epilepsy
• Essential Tremor
• Memory Consolidation
• Memory Disorders
• Memory Encoding
• Memory Replay
• Motor Abilities
• Seizures

Eligibility Criteria

Sex

ALL

Age

18 Years - 70 Years

Healthy Volunteers

Not accepted

Interventions

• Cobenfy KarXT pill (50/20 mg) — DRUG
  Subjects will receive Cobenfy KarXT pill (50/20 mg) 2 hours prior to surgery.
• Placebo — DRUG
  Subjects will receive placebo pill (equivalent of 50/20mg) 2 hours prior to surgery.

Study Details

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.

Key Dates

First listed

Jul 23, 2026

Start date

Oct 31, 2026

Status verified

Jul 2026

Primary completion

Sep 30, 2030

Completion

Sep 30, 2030

Study Design

Enrollment

30 participants (estimated)

Allocation

RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

BASIC_SCIENCE

Arms

• Placebo Comparator: Essential Tremor w/Placebo
  Subjects will receive placebo pill (equivalent of 50/20mg) 2 hours prior to surgery. During awake surgery, the participant will complete either an episodic memory, a spatial memory, a working memory, or a cognitive control task session.
• Experimental: Essential Tremor w/Cobenfy KarXT (xanomeline and trospium chloride)
  Subjects will receive Cobenfy KarXT pill (50/20 mg) 2 hours prior to surgery. During awake surgery, the participant will complete either an episodic memory, a spatial memory, a working memory, or a cognitive control task session.
• Placebo Comparator: Epilepsy w/Placebo
  Subjects will receive placebo pill (equivalent of 50/20mg) 2 hours prior to surgery. A passive recording with the patient under anesthesia during placebo state will be conducted in order to observe layer-specific baseline firing rate that can be linked with extraoperative ex vivo and in vivo recordings in other contexts.
• Experimental: Epilepsy w/Cobenfy KarXT (xanomeline and trospium chloride)
  Subjects will receive Cobenfy KarXT pill (50/20 mg) 2 hours prior to surgery. A passive recording with the patient under anesthesia during cholinergic manipulation will be conducted in order to observe layer-specific changes in firing rate that can be linked with extraoperative ex vivo and in vivo recordings in other contexts.

Primary Outcome Measure

Cognitive control task-related changes in brain electrical activity in participants from baseline at cholinergic modulation post-intervention (approx. within 2-5 hrs) [ Time Frame: Baseline, at cholinergic modulation post-intervention (approx. within 2-5 hrs) ]

Central Contacts

• Bradley C Lega, MD
  214-648-7816
  [email protected]

Locations (1)

Find similar trials in Dallas, TX

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