Scopolamine for Memory Loss

Overseen By Bradley Lega, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Cannabinoids, Cocaine, Amphetamines, Barbiturates

Disqualifiers: Pregnancy, Renal insufficiency, Cardiac syndrome, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the study team to ensure they don't interfere with the trial.

How is the drug scopolamine unique for treating memory loss?

Scopolamine is unique because it is administered through a transdermal patch, which provides a steady release of the drug over three days, potentially minimizing side effects compared to oral or injectable forms. It acts as a muscarinic antagonist, which means it blocks certain receptors in the brain, and is being studied for its effects on memory and cognition. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Scopolamine for memory loss?

The research indicates that scopolamine can cause temporary memory impairments, which are used as a model to study Alzheimer's disease. However, there is no direct evidence from the provided studies that scopolamine is effective in treating memory loss; instead, it is used to simulate memory deficits for research purposes. ^{1 4 6 7 8}

Who Is on the Research Team?

Bradley Lega, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with epilepsy, in good health otherwise, and scheduled for intracranial surgery. They must have a BMI of 18-35 kg/m2 and be able to consent. Excluded are those with significant health issues like heart problems, liver failure, certain neurological conditions, glaucoma, gastrointestinal blockages or pregnant women.

Inclusion Criteria

Able to read, understand, and provide written, dated informed consent prior to screening.

Your body mass index (BMI) is between 18 and 35.

My doctor has recommended I undergo a detailed brain monitoring procedure for epilepsy.

Exclusion Criteria

I have been diagnosed with an enlarged prostate.

I have a nerve condition caused by my immune system.

I have a history of narrow-angle glaucoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either scopolamine or saline and complete memory tasks

2 days

2 visits (in-person)

Follow-up

Participants are monitored for memory-related changes in brain electrical activity

1-3 hours post-intervention each day

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Scopolamine

Trial Overview The study tests how scopolamine affects memory-related brain activity in epileptic patients during surgery. Participants receive either the drug or a placebo on different days while completing memory tasks. Brain activity is recorded to see if scopolamine influences memory encoding or retrieval.

How Is the Trial Designed?

Group I: Scopolamine (0.4mg) Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Scopolamine is already approved in United States, Canada for the following indications:

Approved in United States as Transderm-Scop for:

• Prevention of nausea and vomiting after anesthesia, narcotic pain medicines, and surgery
• Prevention of nausea and vomiting caused by motion sickness

Approved in Canada as Transderm-V for:

• Prevention of nausea and vomiting after anesthesia, narcotic pain medicines, and surgery
• Prevention of nausea and vomiting caused by motion sickness

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Chronic transdermal administration of scopolamine for 72 hours resulted in sustained impairments in visual function, such as near-point vision and pupil size, indicating ongoing peripheral effects.

Memory and attention impairments peaked one day after patch application but were not present three days later, suggesting that while scopolamine can model certain aspects of Alzheimer's disease, its effects on memory may be temporary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The scopolamine model of dementia: chronic transdermal administration. Brazell, C., Preston, GC., Ward, C., et al.[2011]

FK960, a novel antidementia drug, effectively improved visual recognition memory deficits in rhesus monkeys caused by scopolamine, indicating its potential to counteract cholinergic dysfunction associated with dementia.

In comparison to physostigmine, which also restored memory deficits, FK960 showed promise in enhancing memory performance without significant side effects when administered alone, suggesting its therapeutic potential for treating dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: comparison with physostigmine. Matsuoka, N., Aigner, TG.[2018]

Tacrine effectively blocked the learning deficits caused by lower doses of scopolamine, anisodine, atropine, and anisodamine in mice, indicating its potential as a cognitive enhancer against these amnesic agents.

While tacrine showed strong antagonistic effects on avoidance-learning deficits, it was less effective against higher doses of the same amnesic agents, suggesting a dose-dependent response in its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learning deficits induced by 4 belladonna alkaloids are preferentially attenuated by tacrine. Pan, SY., Han, YF.[2019]

In a study involving 10 healthy male volunteers, subcutaneous administration of scopolamine led to dose- and time-dependent impairments in attention and memory, along with significant changes in brain wave activity as measured by quantitative electroencephalogram (qEEG).

The maximum serum concentrations of scopolamine were reached within 10 to 30 minutes after administration, indicating a rapid onset of effects, and the findings suggest that this model could be useful for studying cognitive impairments, such as those related to aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration. Ebert, U., Siepmann, M., Oertel, R., et al.[2022]

A continuous transdermal delivery system for physostigmine was tested over 2 weeks in 12 Alzheimer's Disease patients, showing no major adverse effects and stable plasma concentrations of the drug.

Six out of 12 patients reported improvements in vigilance and concentration, with enhanced scores in neuropsychological tests, suggesting that this delivery method may be effective for some individuals with Alzheimer's Disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal physostigmine in the treatment of Alzheimer's disease. Levy, A., Brandeis, R., Treves, TA., et al.[2019]

Two choline pivaloyl esters were tested in rats with memory impairments caused by scopolamine or lesions in the nucleus basalis magnocellularis, showing significant improvements in both object recognition and spatial memory.

The effects of these compounds were comparable to Tacrine, a known cognitive enhancer, suggesting that they may be effective alternatives for treating memory deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline pivaloyl esters improve in rats cognitive and memory performances impaired by scopolamine treatment or lesions of the nucleus basalis of Meynert. Rispoli, V., Rotiroti, D., Carelli, V., et al.[2018]

In a study involving 33 healthy volunteers, a transdermal scopolamine patch did not show significant effects on emotional cognition or memory, indicating it may not be effective for antidepressant purposes.

The results suggest that the dose of scopolamine delivered through the patch is likely too low to produce the cognitive and antidepressant effects seen with other administration methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overnight transdermal scopolamine patch administration has no clear effect on cognition and emotional processing in healthy volunteers. Bukala, BR., Browning, M., Cowen, PJ., et al.[2023]

Scopolamine is an effective treatment for motion sickness and is commonly used for premedication before anesthesia due to its ability to inhibit muscarinic receptors, leading to antiemetic and sedative effects.

The transdermal patch form of scopolamine improves its bioavailability and reduces side effects compared to oral administration, allowing for a steady release of the drug over 72 hours, which helps maintain effective plasma levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Renner, UD., Oertel, R., Kirch, W.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

The scopolamine model of dementia: chronic transdermal administration. [2011]

2. United States pubmed.ncbi.nlm.nih.gov

FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: comparison with physostigmine. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Learning deficits induced by 4 belladonna alkaloids are preferentially attenuated by tacrine. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Transdermal physostigmine in the treatment of Alzheimer's disease. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Choline pivaloyl esters improve in rats cognitive and memory performances impaired by scopolamine treatment or lesions of the nucleus basalis of Meynert. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Overnight transdermal scopolamine patch administration has no clear effect on cognition and emotional processing in healthy volunteers. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. [2022]