Pharmacological Modulation of Brain Oscillations in Memory Processing

NCT05594017 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: STU 022018-005R01NS125250
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to learn about the effects of scopolamine (an anticholinergic drug) on areas of the brain involved in memory, and changes it may have on brain activity. The investigators will do this by testing epileptic patients who are already undergoing intracranial surgery for seizure monitoring, and measuring the activity from the brain areas being assessed. The main questions it aims to answer are 1) whether scopolamine changes memory activity solely at encoding (the time when the person perceives and determines to remember an item or event) as has previously been found, or if it also can selectively impact retrieval (when the item or event which has been processed is recalled or remembered), and 2) what the nature of the brain activity changes is. Participants will complete two treatment arms. One of these will be with the drug, and the other will be with a saline solution, so that the participants are unaware which session the actual drug has been received. Patients will complete a verbal and/or spatial task each of the two days. An anesthesiologist will administer either the drug or the saline at a critical point which addresses both of the research questions. Researchers will compare the brain activity between the two treatment arms to determine what brain activity changes, and at what time point during memory formation.

Conditions

Epilepsy; Seizures; Cognitive Impairment, Mild; Memory Disorders; Memory Loss

Keywords

oscillatory changes; cholinergic antagonist; muscarinic antagonist

Outcome Measures

Primary Outcomes (8)

• Memory-related changes in brain electrical activity in participants from baseline at Day 1 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the Free recall memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 1 post-intervention (approx. within 1-3 hrs)

• Memory-related changes in brain electrical activity in participants from baseline at Day 2 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the Free recall memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 2 post-intervention (approx. within 1-3 hrs)

• Memory-related changes in brain electrical activity in participants from baseline at Day 1 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the Spatial memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 1 post-intervention (approx. within 1-3 hrs)

• Memory-related changes in brain electrical activity in participants from baseline at Day 2 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the Spatial memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 2 post-intervention (approx. within 1-3 hrs)

• Memory-related changes in brain electrical activity in participants from baseline at Day 1 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the serial recall memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 1 post-intervention (approx. within 1-3 hrs)

• Memory-related changes in brain electrical activity in participants from baseline at Day 2 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the serial recall memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 2 post-intervention (approx. within 1-3 hrs)

• Memory-related changes in brain electrical activity in participants from baseline at Day 1 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the associative recognition memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 1 post-intervention (approx. within 1-3 hrs)

• Memory-related changes in brain electrical activity in participants from baseline at Day 2 post-intervention (approx. within 1-3 hrs)

  Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the associative recognition memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta changes.

  Baseline, at Day 2 post-intervention (approx. within 1-3 hrs)

Study Arms (2)

Scopolamine (0.4mg)

EXPERIMENTAL

Subjects will receive a dose of scopolamine (0.4mg) on each day. Approximately 15 minutes after administration, the participant will then complete either an episodic or a spatial memory task session. If the patient completed the sham session already, this session will take place the day following the initial session, or at least four half-lives after the first session.

Drug: Scopolamine (0.4mg)

Placebo

PLACEBO COMPARATOR

Subjects will receive saline (0.4mg) via IV on each day. Approximately 15 minutes after administration, the participant will then complete either an episodic or a spatial memory task session. If the patient completed the scopolamine session already, this session will take place the day following the initial session, or at least four half-lives after the first session.

Drug: Placebo

Interventions

Scopolamine (0.4mg) DRUG

Patient receives a dose of scopolamine (0.4mg) via IV fifteen minutes prior to spatial or episodic memory task/completion.

Scopolamine (0.4mg)

Placebo DRUG

Patient receives a dose of saline via IV fifteen minutes prior to spatial or episodic memory task/completion.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 - 55 years, all races/ethnicities, and both genders are eligible.
• Candidates for pre-operative evaluation using stereo intracranial electrodes and admission to the Epilepsy Monitoring Unit (EMU) as determined independently by the patient's treating physician as part of the patient's routine medical care.
• Able to read, understand, and provide written, dated informed consent prior to screening.
• In good general health, aside from a history of epilepsy, as ascertained by medical history, physical examination (PE), clinical laboratory evaluations, and ECG.
• Body mass index between 18-35 kg/m2.

You may not qualify if:

• Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results according to the study physician.
• Female that is pregnant, breastfeeding, or has a positive pregnancy test at screening or baseline. Note that pregnant patients are excluded from undergoing iEEG generally and all patients undergo a positive screening urine test for drugs of abuse at screening: cannabinoids, cocaine, amphetamines, barbiturates, opiates not otherwise explained by their prescribed medications.
• History of renal insufficiency.
• Unstable cardiac syndrome or active cardiac symptoms.
• Patients with liver failure.
• Patients with BPH.
• Patients with autoimmune neuropathy.
• Patients with uncontrolled hyperthyroidism.
• Patients with a history of dementia.
• Patient with a history of delirium after using transdermal scopolamine.
• History of narrow-angle glaucoma.
• History of pyloric obstruction or paralytic ileus.
• History of myasthenia gravis, obstructive uropathy, porphyria, or myasthenia gravis.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Epilepsy; Seizures; Cognitive Dysfunction; Memory Disorders

Interventions

Scopolamine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Bradley C Lega, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bradley Lega, MD

CONTACT

214-648-7816; Bradley.Lega@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSOC PROFESSOR - Neurological Surgery

Model Details: Patients are randomized to scopolamine or saline solution by the pharmacy upon drug receipt. Both researchers and patients are blinded to which session receives pharmaceutical versus placebo administration. Each of the patients receive scopolamine or placebo on Day 1 and Day 2 before completing tasks at critical time points to parse encoding and retrieval.

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 26, 2022
• Study Start: August 1, 2019
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)