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Number of Visits: 2

Scopolamine for Muscarinic Receptor Engagement
(emo_to2 Trial)

Overseen ByMark F Dias, MA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Anticholinergics, Antidepressants, Antipsychotics, others

Disqualifiers: Respiratory, Neurological, Psychiatric, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. You cannot use prescription medications, drugs with anticholinergic properties, or strong CYP3A4 inhibitors within 14 days of scopolamine dosing. CYP3A4 inducers should not be taken within 21 days of scopolamine administration.

What data supports the effectiveness of the drug Scopolamine for muscarinic receptor engagement?

Research on muscarinic receptor agonists, which are similar to Scopolamine, shows that they can improve cognitive function in Alzheimer's patients by enhancing cholinergic activity. This suggests that Scopolamine might also engage muscarinic receptors effectively, potentially benefiting conditions related to cognitive function.¹ ² ³ ⁴ ⁵

Is scopolamine safe for humans?

Scopolamine, used in patches for motion sickness, is generally safe but can cause side effects like blurred vision, dry mouth, and dizziness. Some people may have allergic reactions to the patch, and using too many patches at once can be dangerous.⁶ ⁷ ⁸ ⁹ ¹⁰

How does the drug scopolamine differ from other treatments for muscarinic receptor engagement?

Scopolamine is unique because it is delivered through a transdermal patch, which provides a steady release of the drug over three days, minimizing side effects compared to oral or injectable forms. This method helps maintain consistent drug levels in the body, making it effective for conditions like motion sickness and pre-anesthesia, where stable dosing is beneficial.¹¹ ¹² ¹³ ¹⁴ ¹⁵

What is the purpose of this trial?

The purpose of this study is to assess the target occupancy (TO) of scopolamine at M1 Muscarinic Receptors in the brain after single I.V. doses of scopolamine, in healthy control subjects, using the radiotracer \[11C\]EMO (also known as \[11C\]LSN3172176).

Research Team

David Matuskey, MD

Principal Investigator

Yale University

Eligibility Criteria

Healthy adults aged 18-60 who can consent, read, write, and follow study directions. They must be in good health based on medical history, exams, and tests. Excluded are those with hepatitis B/C or HIV; IV drug use history; abnormal lab results or ECG; pregnant/lactating women; recent prescription meds users (with exceptions); scopolamine patch users within 14 days; participants in other trials recently involving drugs or radiotracers; current smokers/nicotine users; substance abuse history within 2 years; positive drug screening.

Inclusion Criteria

My overall health is good based on recent medical exams and tests.

Willing and able to give voluntary, written informed consent

I can read, write, and follow all study instructions.

Exclusion Criteria

Positive drug test at screening

Laboratory tests with clinically significant abnormalities or positive urine toxicology, at screening

Abnormal and clinically significant ECG, as determined by the Investigator or his/her designee, at screening

See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo a baseline PET scan and MRI scan of the brain

1 day

1 visit (in-person)

Treatment and Post-dose Imaging

Participants receive a 15-minute IV infusion of scopolamine followed by a post-dose PET scan

1-2 days

1-2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 48 hours

Treatment Details

Interventions

Scopolamine

Trial Overview The trial is testing how the body's M1 Muscarinic Receptors in the brain respond to different doses of scopolamine given intravenously. It uses a special imaging tracer called [11C]EMO ([11C]LSN3172176) during PET and MRI scans to measure this response in healthy volunteers.

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Scopolamine low doseExperimental Treatment2 Interventions

The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer \[11C\]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 2.0 μg/kg scopolamine in 0-2 anticipated participants.

Group II: Scopolamine high doseExperimental Treatment2 Interventions

The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer \[11C\]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 4.0 μg/kg scopolamine in 4-6 anticipated participants.

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Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

Findings from Research

Rivastigmine, a cholinesterase inhibitor for Alzheimer's disease, is available in both oral and transdermal patch forms, with the patch showing better tolerability across all stages of the disease compared to the oral form and other cholinesterase inhibitors.

While the transdermal patch formulation is generally safer, there is a risk of overdose if multiple patches are used simultaneously, highlighting the importance of patient and caregiver education on proper usage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of current therapies for Alzheimer's disease: focus on rivastigmine.Khoury, R., Rajamanickam, J., Grossberg, GT.[2020]

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]