PET and MRI Imaging With Scopolamine at the Muscarinic M1 Receptor

• Status: Not yet recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Yale University
• Collaborator: Janssen Scientific Affairs, LLC
• Treatments: Butylscopolammonium Bromide; LSN3172176; Scopolamine

Criteria

Inclusion Criteria:

• Willing and able to give voluntary, written informed consent

• Have the ability to read and write, communicate effectively with the investigator and to comply with all study requirements, restrictions, and directions of the research staff.

• Male or female, aged Age 18 to 60 years inclusive, at screening.

• In good general health as evidenced by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests.

Exclusion Criteria:

• History or presence of clinically significant respiratory, GI, renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers.

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

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

• Seropositive for hepatitis B, hepatitis C, and/or HIV

• Pregnancy or lactation

• Use of prescription medications within 14 days of scopolamine dosing. Exceptions may be allowed only if the medication's administration is deemed unlikely to impact the study result.

• Current or recent use (within 14 days) of scopolamine transdermal patch, for any reason (ex: for motion sickness).

• Use of drugs with anticholinergic properties within 14 days of scopolamine dosing, for example, belladonna alkaloids, first generation antihistamines, antidepressants (tricyclics and MAO inhibitors), phenothiazines and second generation antipsychotics (clozapine and olanzapine), amantadine and quinidine. Non-sedating antihistamines (e.g., loratadine) use is acceptable.

• Strong CYP3A4 inhibitors such as itraconazole and grapefruit juice should also not be taken within 14 days of receiving scopolamine. Use of CYP3A4 inducers (e.g., carbamazepine, rifampin) should not be taken within 21 days of scopolamine administration.

• Treatment with another investigational drug or other intervention within 30 days of the screening visit, or participation in another trial involving radiotracer administration within 1 week of dosing day.

• Current smoker (including any form of nicotine use)

• History of alcohol or drug abuse, within 2 years prior to screening, as determined by the investigator.

• Positive drug test at screening

• Blood donation within eight weeks of the start of the study. Subjects that confirm recent blood donation may reschedule for a later screening date.

• History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).

• Unable to safely discontinue or hold aspirin and other NSAID use, as outlined in Section 6.1.8

• MRI incompatible implants (i.e., such as pacemaker, artificial joints, non-removable body piercings) and other contraindications for MRI, such as claustrophobia, having implanted or embedded metal objects/fragments or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist).

• Participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits for healthy volunteers set by the Yale University PET Center. This limit follows the guidelines listed in 21 CFR 361.1 for research subjects.

• Subjects with a history of IV drug use that would prevent venous access for PET tracer injection.

• Subject who has current, past, or anticipated exposure to radiation in the work place within one year of the proposed research scans that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits.

• Has any condition that, in the opinion of the investigator, would prevent compliance with the study protocol.