Cholinergic Mechanisms of Attention in Aging

NCT04756232 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 210003
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study will use an anticholinergic pharmacological probe to examine attention network function in SCD using EEG. The overall hypothesis is that in older adults with SCD, normal cognitive performance is maintained by compensatory attention network activity, supported by enhanced cholinergic function. The investigators anticipate that SCD will be associated with greater compensatory attention network activity and that disrupting this compensatory process through anticholinergic challenge will result in a greater negative effect on attentional performance (Attention Network Test, ANT) and attention network functioning (EEG) in older adults with SCD compared to those without SCD.

Conditions

Subjective Cognitive Decline

Outcome Measures

Primary Outcomes (2)

• Proportion of participants who complete study visits with drug challenge

  Proportion of particiapnts who complete study days as measured by study drug administration on both study visits with drug challenge

  After administration of second drug challenge, approximately 72 hours

• Proportion of participants who complete EEG

  Proportion of participants who complete EEG sessions as measured by adminstration of EEG

  After administration of second drug challenge, approximately 72 hours

Study Arms (2)

Anticholinergic Challenge

EXPERIMENTAL

All participants will receive oral mecamylamine or IV scopolamine for 1 day

Drug: Mecamylamine Challenge

Placebo Challenge

PLACEBO COMPARATOR

All participants will receive oral placebo for 1 day

Other: Placebo Comparator Challenge

Interventions

Mecamylamine Challenge DRUG

Mecamylamine 20 mg oral pill administered once

Anticholinergic Challenge

Placebo Comparator Challenge OTHER

Matching placebo oral pill administered once

Placebo Challenge

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥ 55
• Montreal Cognitive Assessment (MoCA) \> 25 AND Global Deterioration Scale (GDS) rating \< 3
• Non-smokers

You may not qualify if:

• medical contraindications to the drug challenge
• primary neurological disorder (such as stroke, epilepsy, etc.)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Study Officials

• Paul Newhouse, MD

  Vanderbilt University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Instructor, Psychiatry

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 16, 2021
• Study Start: April 21, 2022
• Primary Completion: April 30, 2025
• Study Completion: May 1, 2025
• Last Updated: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)