Effects of Nicotine and Attention on Frequency Tuning in Auditory Cortex

NCT05018117 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 2018-12-11682R01AG067073-01A1
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Nicotine enhances auditory-cognitive function because it mimics the brain's system for "paying attention" to important sounds amid distractions (for example, understanding speech in a noisy environment). In part, nicotine does this by activating inhibitory neurons in the auditory cortex. Since age-related hearing deficits result, in part, from the loss of inhibitory neurons in auditory cortex, this project will determine whether nicotine's effects can compensate for reduced inhibition in the aging auditory cortex and thereby restore auditory function. The investigators will use functional magnetic resonance imaging (fMRI) to measure the selectivity of responses in auditory cortex to tones of various frequencies. The investigators will measure the effects of nicotine (administered as chewing gum) and aging on these fMRI response properties. The investigators hypothesize that frequency selectivity will decrease with aging and increase following nicotine administration.

Conditions

Aging

Keywords

nicotine; acetylcholine; functional magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• frequency tuning of excitatory auditory fMRI cortical responses

  Functional magnetic resonance imaging (fMRI) responses to pure tone stimuli ranging from 88-8000 Hz will be recorded. For each voxel in objectively identified auditory cortical area, a tuning curve model will be fit to the data. One of the parameters of this model is the width of frequency tuning of excitatory responses, and this is the primary outcome measure.

  Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours.

Secondary Outcomes (3)

• frequency tuning of inhibitory auditory fMRI cortical responses

  Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours.

• amplitude of excitatory auditory fMRI cortical responses

  Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours.

• amplitude of inhibitory auditory fMRI cortical responses

  Functional MRI recordings will begin approximately 30 minutes after oral administration of polacrilex or placebo gum and will continue for up to two hours.

Study Arms (4)

Young (18-28 years) participants - nicotine gum

EXPERIMENTAL

6 mg nicotine gum, one time before fMRI measurements

Drug: Nicotine gum

Old (60-85 years) participants - nicotine gum

EXPERIMENTAL

6 mg nicotine gum, one time before fMRI measurements

Drug: Nicotine gum

Young (18-28 years) participants - placebo gum

PLACEBO COMPARATOR

placebo gum, one time before fMRI measurements

Other: Placebo gum

Old (60-85 years) participants - placebo gum

PLACEBO COMPARATOR

placebo gum, one time before fMRI measurements

Other: Placebo gum

Interventions

Nicotine gum DRUG

The effects of over-the-counter nicotine gum will be compared to a placebo gum

Also known as: polacrilex

Old (60-85 years) participants - nicotine gum; Young (18-28 years) participants - nicotine gum

Placebo gum OTHER

The effects of over-the-counter nicotine gum will be compared to a placebo gum

Old (60-85 years) participants - placebo gum; Young (18-28 years) participants - placebo gum

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• non-smokers with a score of 0-2 out of 10 maximum on the Fagerström index of smoking dependency

You may not qualify if:

• deafness or excessive hearing loss
• smokers with a score between 3 and 10 on the Fagerström index of smoking dependency
• history of psychiatric illness, neurological disorders, diabetes mellitus, renal failure, or cardiovascular disease
• regular use of prescription medications (excluding oral contraceptives)
• drug dependency

Sponsors & Collaborators

• University of California, Berkeley: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of California, Berkeley

Berkeley, California, 94720, United States

RECRUITING

MeSH Terms

Interventions

Nicotine Chewing Gum; Tobacco Use Cessation Devices

Intervention Hierarchy (Ancestors)

Chewing Gum; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Therapeutics; Candy; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Michael A Silver, PhD

  University of California, Berkeley

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael A Silver, PhD

CONTACT

5106423130; masilver@berkeley.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Nicotine (6 mg, polacrilex gum) and placebo will be administered to each participant in separate sessions in a within-subject double-blind randomized crossover design. Subjects will be in either a young (18-28 years) or old (60-85 years) group.

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 24, 2021
• Study Start: June 6, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)