The Nicotinic Cholinergic System and Cognitive Aging

NCT03408574 | Completed Phase 1 FDA Drug

• 1 other identifier: CHRMS 16-284
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

Prior research has shown that a chemical system in the brain called the cholinergic system is primarily responsible for cognitive symptoms seen in people with dementia. While therapeutic benefits are clear in dementia, what remains uncertain is the role that the cholinergic system in general and a subset of receptors called the nicotinic system plays in cognition in healthy non-demented older adults (referred to as normal cognitive aging). This is critical because the ever growing healthy aging population will show declines in cognition that fall short of dementia but still impact functional abilities and independence. Maintaining good nicotinic system functioning throughout adulthood may lessen the cognitive symptoms of aging. At this time, it is not clear what the biological cause of age-related changes in cognition is. This study will examine the role of the nicotinic system in the healthy aging brain and examine its role in memory and thinking processes in older and younger adults.

Conditions

Healthy Aging

Keywords

nicotinic system; cognitive aging; working memory; fMRI

Outcome Measures

Primary Outcomes (2)

• Age effects of nicotinic blockade

  Examine the effects of nicotinic blockade compared to placebo on the relationship between working memory performance and brain activation using fMRI BOLD signal in older and younger adults.

  After the completion of the third study day.

• Age effects of nicotinic stimulation

  Examine the effects of nicotinic stimulation compared to placebo on the relationship between working memory performance and brain activation using fMRI BOLD signal in older and younger adults.

  After the completion of the third study day.

Study Arms (2)

Older Adults

EXPERIMENTAL

Healthy adults aged 65-75 will participate in three study days where they are randomly assigned to receive either nicotine patch, oral mecamylamine, placebo and perform a working memory task during the fMRI. BOLD signal is the outcome measure.

Drug: Nicotine patch, oral mecamylamine, placebo

Younger Adults

EXPERIMENTAL

Healthy adults aged 18-30 will participate in three study days where they are randomly assigned to receive either nicotine patch, oral mecamylamine, or placebo and perform a working memory task during the fMRI.BOLD signal is the outcome measure.

Drug: Nicotine patch, oral mecamylamine, placebo

Interventions

Nicotine patch, oral mecamylamine, placebo DRUG

Each participant randomly receives one active drug or placebo on each of three study days.

Older Adults; Younger Adults

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Normal cognition, not demented, no mild cognitive impairment. IQ greater than 80.

You may not qualify if:

• Current use of barbiturates, rifampin, insulin, carbamezepine, oral hypoglycemics, antidepressants, diabetes, or untreated thyroid disease.
• Current use of centrally active drugs and drugs with cholinergic properties. A minimum of 14 days will elapse between discontinuing centrally active or psychoactive agents and this study.

Sponsors & Collaborators

• University of Vermont: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

University of Vermont

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Interventions

Tobacco Use Cessation Devices; Mecamylamine

Intervention Hierarchy (Ancestors)

Therapeutics; Norbornanes; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Julie A Dumas, Ph.D.

  University of Vermont

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double blind study. The PI and all study personnel are blinded. Only the pharmacist dispensing the medication and the biostatistician who created the counterbalancing order are unblended.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Healthy older adults aged 65-75 and healthy younger adults aged 18-30 will be recruited. Each participant will take part in 3 nicotinic drug challenge days. The three drugs are counterbalanced across study days within each group and balanced by sex.

Study Record Dates

• First Submitted: January 3, 2018
• First Posted: January 24, 2018
• Study Start: October 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: January 31, 2022
• Last Updated: May 9, 2023

Record last verified: 2023-05

Locations

US (1)