Scopolamine or PlaceboEarly Phase 1NCT07423923
Representation of Spatiotemporal Information in Human Episodic Memory and Navigation
A Early Phase 1 study testing Scopolamine in people with Scopolamine or Placebo and Schema to Organize Memory or no Schema, run by University of Arizona at 2 sites in United States.
Trial summary
Neural diseases such as stroke can have distinct effects on the ability to navigate and orient compared to remembering daily events like when one last took medicine. This proposal seeks test rival hypotheses regarding the neural mechanisms underlying commonalities and differences in navigation and event-related… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Scopolamine or Placebo, Schema to Organize Memory or no Schema
- What is being tested?
- Scopolamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Apr 2025to 29 Mar 2030
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Inclusion Criteria (for healthy young adults in fMRI studies)
- Able to provide verbal and written informed consent
- Fluent English speaker
- At least 8th grade education
- Age between 18-40 years.
- Normal or corrected-to-normal eyesight
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- Exclusion Criteria (for healthy young adults in fMRI studies)
- Magnetic resonance imaging contraindications (e.g., metallic objects in body, claustrophobia)
- Current use of anticonvulsant, neuroleptic, sedatives, or other medications known to affect cognition
- Neurologic conditions affecting the brain (e.g., stroke, epilepsy, traumatic brain injury with loss of consciousness)
- Psychiatric conditions (e.g., major depression, schizophrenia)
- Patient inclusion criteria for iEEG:
- 1. Adult patients with medically refractory epilepsy who are scheduled to undergo or have previously undergone placement of sub-dural electrodes or depth electrodes or stereo-electroencephalography to localize the site of seizure onset.
Who cannot join
- Patients with gross structural abnormalities (hematoma, tumors, large vascular malformations, diffuse malformations of cortical development) that may impact critical perceptual or memory areas needed to perform tasks.
- Patients who are unable to participate in memory testing due to impaired cognition or mental retardation. All patients routinely undergo a detailed neuropsychological evaluation, and the neuropsychological report will be used to make this assessment.
- Patients/volunteers with cardiac pacemakers, intracranial aneurysm clips, or other potentially mobile implanted metallic devices cannot be included in this study, because of possible effects of high power magnetic fields on them.
- Patients with claustrophobia who cannot undergo an MRI scan without sedation.
- Pregnant women
- Patient inclusion criteria for scopolamine:
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- 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.
- Patient exclusion criteria:
- History of renal insufficiency.
- Patients with liver failure.
- 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 (due to increased eye pressure).
- History of pyloric obstruction or paralytic ileus.
- History of myasthenia gravis, obstructive uropathy, porphyria, or myasthenia gravis.
- -
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
University of Texas Southwestern Medical Center / O'Donnell Brain Institute
Dallas, Texas, 75390
University of Arizona Psychology Department and Evelyn McKnight Brain Institute
Tucson, Arizona, 85721
About this study
Neural diseases such as stroke can have distinct effects on the ability to navigate and orient compared to remembering daily events like when one last took medicine. This proposal seeks test rival hypotheses regarding the neural mechanisms underlying commonalities and differences in navigation and event-related memory, particularly as they relate to pre-existing knowledge. Such mechanistic insight could help inspire therapies that could be used to bolster intact brain function in a compensatory manner following strokes or other neural insults.
Read the detailed description
Contemporary models of spatial navigation and episodic memory (memory for events) postulate that their underlying computations emerge primarily from shared neural mechanisms within the medial temporal lobes. As part of the last two rounds of funding for this competitive renewal, the investigators began delineation of important cognitive and neural differences between navigation and episodic memory. The emerging new framework argues for navigation as a sensory-driven cognitive motor skill involving extracting spatial regularities and episodic memory as primarily internally driven and involving ordinal placeholders. The investigators hypothesize that navigation and episodic memory therefore involve partially distinct brain regions and macroscale networks, although where and how these differences emerge in the brain remains an area of active exploration. Here, the investigators test novel aspects of this theoretical framework: how pre-existing knowledge differentially affects the acquisition of new episodic memories compared to navigation-related representations over both longer (days and weeks; Aim 1) and shorter (hours; Aim 2) intervals. Throughout, the investigators propose meaningful alternative models, including the idea that connectivity to the hippocampus and neocortex, and cortical macroscale networks outside of the hippocampus, play critical and unique roles in episodic memory compared to navigation. In Aim 1, using high-resolution fMRI, the investigators propose to employ three different experiments to compare how schema (pre-existing spatial knowledge) and scripts (pre-existing temporal knowledge) differentially interact with new learning in the context of episodic memory and navigation. Together, the outcomes from these experiments will provide mechanistic insight into how humans organize episodic memories and navigation-relevant knowledge over longer intervals that could be meaningful for cognitive rehabilitation. In Aim 2, the investigators focus on how episodic memory interacts with navigation and pre-existing knowledge over shorter-term intervals (hours) by studying mental simulation before and after navigation. Mental simulation involves actively remembering or planning experiences and has direct links with cognitive processes central to episodic memory, particularly in our three different proposed experiments. Here, the PI's team will employ time-resolved intracranial EEG in conjunction with Dr. Brad Lega at University of Texas Southwestern to better identify the mnemonic content of both navigation and mental simulation, including a causal manipulation involving the muscarinic acetylcholine antagonist scopolamine and single cell recordings. Together, the experiments in Aim 2 will provide novel insight into the mechanistic basis of episodic memory and navigation-related representations. Such mechanistic could be helpful in developing neurostimulation or pharmacological protocols (e.g., involving acetylcholine) that could be used to bolster either impaired memory or navigation function following stroke, seizure damage, or other brain injuries affecting hippocampal function.
- Being tested
- Scopolamine
- Keywords
- scopolamine, memory training, hippocampus, brain oscillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ScopolamineDrug
effects of scopolamine on brain oscillations, navigation, and memory
| Study group | Role | What they receive |
|---|---|---|
| Patients undergoing surgical monitoring to plan resections for epilepsy | Experimental | Patients will have electrodes implanted in their hippocampus for surgical monitoring allowing for direct recordings. Patients will receive scopolamine on one day and placebo on another. Receives: Drug: Scopolamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
behavioral: navigational accuracy
accuracy (path error) of routes taken in virtual environment
Measured: from enrollment to end of study (3 days)
intracranial EEG low-frequency oscillatory power
approximate amplitude of signal recorded from the hippocampus of patients undergoing seizure monitoring
Measured: from enrollment to the end of study (3 days)
memory accuracy (as part of memory training component involving healthy controls)
how many words remembered
Measured: from enrollment to the end of study (3 weeks)
Route replay time
time (in seconds) it takes to remember a route that will or has been taken
Measured: from enrollment to the end of study (3 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study start1 Apr 2025
- Primary completion29 Mar 2030 (estimated)
- Study completion29 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Scopolamine or PlaceboStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- University of Texas
- Responsible party
- Sponsor
- Investigators
- Arne Ekstrom, Ph.D., Principal investigator, University of Arizona McKnight Brain InstituteBrad Lega, M.D., Study director, University of Texas, Southwestern Medican Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07423923
- Sponsor's protocol ID
- 2R01NS076856-11
- Other IDs
- 2R01NS076856-11
- Status last verified
- Feb 2026
- First submitted
- 6 Feb 2026
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: All data will be anonymized and shared publicly upon publication.
Publications
Seger SE, Kriegel JLS, Lega BC, Ekstrom AD. Memory-related processing is the primary driver of human hippocampal theta oscillations. Neuron. 2023 Oct 4;111(19):3119-3130.e4. doi: 10.1016/j.neuron.2023.06.015. Epub 2023 Jul 18.
PubMed 37467749Zheng L, Boogaart Z, McAvan A, Garren J, Doner SG, Wilkes BJ, Groves W, Yuksel E, Cherep L, Ekstrom A, Weisberg SM. Newly trained navigation and verbal memory skills in humans elicit changes in task-related networks but not brain structure. Elife. 2025 Oct 28;14:RP106873. doi: 10.7554/eLife.106873.
PubMed 41150161
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Representation of Spatiotemporal Information in Human Episodic Memory and Navigation
- ClinicalTrials.gov ID
- NCT07423923
- Acronym / sponsor ID
- 2R01NS076856-11
- Keywords
- scopolamine, memory training, hippocampus, brain oscillation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- University of Texas
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 29 Mar 2030 (estimated)
- Study completion
- 29 Mar 2030 (estimated)
- First posted
- 20 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neural diseases such as stroke can have distinct effects on the ability to navigate and orient compared to remembering daily events like when one last took medicine. This proposal seeks test rival hypotheses regarding the neural mechanisms underlying commonalities and differences in navigation and event-related memory, particularly as they relate to pre-existing knowledge. Such mechanistic insight could help inspire therapies that could be used to bolster intact brain function in a compensatory manner following strokes or other neural insults.
Detailed description
Contemporary models of spatial navigation and episodic memory (memory for events) postulate that their underlying computations emerge primarily from shared neural mechanisms within the medial temporal lobes. As part of the last two rounds of funding for this competitive renewal, the investigators began delineation of important cognitive and neural differences between navigation and episodic memory. The emerging new framework argues for navigation as a sensory-driven cognitive motor skill involving extracting spatial regularities and episodic memory as primarily internally driven and involving ordinal placeholders. The investigators hypothesize that navigation and episodic memory therefore involve partially distinct brain regions and macroscale networks, although where and how these differences emerge in the brain remains an area of active exploration. Here, the investigators test novel aspects of this theoretical framework: how pre-existing knowledge differentially affects the acquisition of new episodic memories compared to navigation-related representations over both longer (days and weeks; Aim 1) and shorter (hours; Aim 2) intervals. Throughout, the investigators propose meaningful alternative models, including the idea that connectivity to the hippocampus and neocortex, and cortical macroscale networks outside of the hippocampus, play critical and unique roles in episodic memory compared to navigation. In Aim 1, using high-resolution fMRI, the investigators propose to employ three different experiments to compare how schema (pre-existing spatial knowledge) and scripts (pre-existing temporal knowledge) differentially interact with new learning in the context of episodic memory and navigation. Together, the outcomes from these experiments will provide mechanistic insight into how humans organize episodic memories and navigation-relevant knowledge over longer intervals that could be meaningful for cognitive rehabilitation. In Aim 2, the investigators focus on how episodic memory interacts with navigation and pre-existing knowledge over shorter-term intervals (hours) by studying mental simulation before and after navigation. Mental simulation involves actively remembering or planning experiences and has direct links with cognitive processes central to episodic memory, particularly in our three different proposed experiments. Here, the PI's team will employ time-resolved intracranial EEG in conjunction with Dr. Brad Lega at University of Texas Southwestern to better identify the mnemonic content of both navigation and mental simulation, including a causal manipulation involving the muscarinic acetylcholine antagonist scopolamine and single cell recordings. Together, the experiments in Aim 2 will provide novel insight into the mechanistic basis of episodic memory and navigation-related representations. Such mechanistic could be helpful in developing neurostimulation or pharmacological protocols (e.g., involving acetylcholine) that could be used to bolster either impaired memory or navigation function following stroke, seizure damage, or other brain injuries affecting hippocampal function.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients undergoing surgical monitoring to plan resections for epilepsy | Experimental | Drug: ScopolaminePatients will have electrodes implanted in their hippocampus for surgical monitoring allowing for direct recordings. Patients will receive scopolamine on one day and placebo on another. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Inclusion Criteria (for healthy young adults in fMRI studies)
- Exclusion Criteria (for healthy young adults in fMRI studies)
- Magnetic resonance imaging contraindications (e.g., metallic objects in body, claustrophobia)
- Current use of anticonvulsant, neuroleptic, sedatives, or other medications known to affect cognition
- Neurologic conditions affecting the brain (e.g., stroke, epilepsy, traumatic brain injury with loss of consciousness)
Key exclusion criteria (19 listed)
- Patients with gross structural abnormalities (hematoma, tumors, large vascular malformations, diffuse malformations of cortical development) that may impact critical perceptual or memory areas needed to perform tasks.
- Patients who are unable to participate in memory testing due to impaired cognition or mental retardation. All patients routinely undergo a detailed neuropsychological evaluation, and the neuropsychological report will be used to make this assessment.
- Patients/volunteers with cardiac pacemakers, intracranial aneurysm clips, or other potentially mobile implanted metallic devices cannot be included in this study, because of possible effects of high power magnetic fields on them.
- Patients with claustrophobia who cannot undergo an MRI scan without sedation.
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Scopolamineeffects of scopolamine on brain oscillations, navigation, and memory | Drug | Patients undergoing surgical monitoring to plan resections for epilepsy |
Primary outcome
behavioral: navigational accuracy
Time frame: from enrollment to end of study (3 days)
accuracy (path error) of routes taken in virtual environment
intracranial EEG low-frequency oscillatory power
Time frame: from enrollment to the end of study (3 days)
approximate amplitude of signal recorded from the hippocampus of patients undergoing seizure monitoring
memory accuracy (as part of memory training component involving healthy controls)
Time frame: from enrollment to the end of study (3 weeks)
how many words remembered
Route replay time
Time frame: from enrollment to the end of study (3 days)
time (in seconds) it takes to remember a route that will or has been taken
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Background: PubMed 37467749Seger SE, Kriegel JLS, Lega BC, Ekstrom AD. Memory-related processing is the primary driver of human hippocampal theta oscillations. Neuron. 2023 Oct 4;111(19):3119-3130.e4. doi: 10.1016/j.neuron.2023.06.015. Epub 2023 Jul 18.
- Background: PubMed 41150161Zheng L, Boogaart Z, McAvan A, Garren J, Doner SG, Wilkes BJ, Groves W, Yuksel E, Cherep L, Ekstrom A, Weisberg SM. Newly trained navigation and verbal memory skills in humans elicit changes in task-related networks but not brain structure. Elife. 2025 Oct 28;14:RP106873. doi: 10.7554/eLife.106873.
- Individual participant dataSharing planned: Undecided. All data will be anonymized and shared publicly upon publication.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Arne Ekstrom, Ph.D. principal investigator
University of Arizona McKnight Brain Institute
Brad Lega, M.D. study director
University of Texas, Southwestern Medican Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Scopolamine in people with Scopolamine or Placebo and Schema to Organize Memory or no Schema, run by University of Arizona at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
behavioral: navigational accuracy (time frame: from enrollment to end of study (3 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07423923, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.