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?

This trial aims to study how scopolamine affects brain activity related to memory. Researchers seek to determine whether it alters memory only during formation or also during recall. Participants will receive either scopolamine or a placebo (a harmless substance resembling the drug) and will complete memory tasks to compare brain activity in both scenarios. The trial seeks epileptic patients already undergoing brain monitoring for seizures. As an Early Phase 1 trial, this research focuses on understanding how scopolamine works in people, offering participants a unique opportunity to contribute to groundbreaking scientific knowledge.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that scopolamine, when injected, has been used in studies to mimic memory loss, indicating its impact on memory. This effect is why it is being tested in this trial. However, side effects such as drowsiness, confusion, and memory problems may occur.

Scopolamine has also been used in other forms, like patches, which can cause serious heat-related issues, such as increased body temperature, sometimes leading to hospitalization. Since this study uses an injectable form, those specific risks might not apply.

This trial is in its early stages. While some safety information is available from other uses, the complete safety details for this specific use are still under investigation. Participants in this trial will help researchers learn more about how well scopolamine is tolerated in this setting. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for memory loss, which often includes medications like cholinesterase inhibitors, scopolamine offers a unique approach by temporarily blocking the action of acetylcholine, a neurotransmitter associated with memory and learning. Researchers are excited because scopolamine's rapid effect allows them to study its impact on episodic and spatial memory tasks shortly after administration. This provides insights into memory processes and could lead to new ways of managing memory loss more effectively and quickly.

What evidence suggests that this trial's treatments could be effective for memory loss?

This trial will compare Scopolamine with a placebo to study its effects on memory. Research has shown that Scopolamine can cause memory loss, making it useful for studying memory function. Studies have found that Scopolamine effectively induces memory problems, aiding researchers in understanding memory loss in conditions like dementia. Although it causes some memory issues, this is precisely why it is being studied—to learn more about how memory is affected and what changes occur in the brain. ^{2 6 7 8 9}

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

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12041729/

The effect of scopolamine on memory and attention This study supports the use of scopolamine as a “memory-loss model,” particularly when given by an injectable route of administration.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167494308001581

Mental confusion associated with scopolamine patch in ... Transdermal scopolamine patch has occasionally been reported to induce mental confusion or cognitive dysfunctions in the elderly (Osterholm and Camoriano, 1982, ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1568163724004537

Beyond the blur: Scopolamine's utility and limits in ... Scopolamine effectively induces memory impairments across species, aiding dementia modeling. ... Despite its non-selectivity, scopolamine is widely used for ...

4. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00182/full

Scopolamine-induced “cholinergic stress test” in the elderly It is well demonstrated that the elderly are more sensitive to the cognitive effects of scopolamine than young individuals, probably due to central cholinergic ...

5. researchgate.net researchgate.net/publication/390602679_The_effect_of_scopolamine_on_memory_and_attention_A_systematic_review_and_meta-analysis

The effect of scopolamine on memory and attention Conclusion This study supports the use of scopolamine as a “memory-loss model,” particularly when given by an injectable route of administration. Future ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/scopolamine-transdermal-route/description/drg-20072848

Scopolamine (transdermal route) - Side effects & dosage Safety and efficacy have not been established. ... loss of memory; muscle cramps; pale, clammy skin; poor coordination; problems with memory ...

7. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-adds-warning-about-serious-risk-heat-related-complications-antinausea-patch-transderm-scop

Serious risk of heat-related complications with Transderm ... The patch can increase body temperature and cause heat-related complications, resulting in hospitalization or even death in some cases.

8. rxlist.com rxlist.com/transderm-scop-drug.htm

Transderm Scop (Scopolamine): Side Effects, Uses, ... Scopolamine can cause drowsiness, disorientation, and confusion. Discontinue TRANSDERM SCÖP if signs or symptoms of cognitive impairment develop ...

9. go.drugbank.com go.drugbank.com/drugs/DB00747

Scopolamine: Uses, Interactions, Mechanism of Action Patients with gastrointestinal or urinary disorders should be monitored frequently for impairments, and scopolamine should be discontinued if these develop.