Using Nicotine to Reverse Age-related Auditory Processing Deficits (Nicotine)

Using Nicotine to Reverse Age-related Auditory Processing Deficits: Human Psychophysics and Electrophysiology

The present study will evaluate the effects of both aging and nicotine on psychophysical tasks and electrophysiological measures. Nicotine will be administered to study participants in the form of gum that is available as an over-the-counter medication. The hypothesis is that nicotine will reverse the detrimental effects of aging on auditory processing. The proposed experiments will characterize the effects of nicotine and may eventually lead to improved treatments of hearing loss in a variety of patient populations and in healthy aging.

Study Overview

• Status: Recruiting
• Conditions: Aging; Auditory Perceptual Impairment
• Intervention / Treatment: Other: Nicotine gum; Other: Placebo gum

Detailed Description

Study participants will be recruited in two age groups: young (18-28 years) and old (60-85). Each participant will participate in two psychophysical and electrophysiological test sessions. For each of the two sessions, the participant will be administered gum before the test. For one of these sessions, the gum will be polacrilex that contains 6-mg nicotine, and for the other session, the gum will be a placebo control. The study will be double-blind, meaning that neither the experimenter nor the participant will know whether the participant has received nicotine or placebo for a given session. The study has a cross-over design, meaning that all participants will receive both nicotine and placebo in separate sessions. Finally, the order of drug administration will be counterbalanced, meaning that equal numbers of participants will receive 1) nicotine in session one and placebo in session two, and 2) placebo in session one and nicotine in session two.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michelle Kapolowicz, PhD; Phone Number: 9498249107; Email: mkapolow@hs.uci.edu

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • Recruiting
      • Hearing and Speech Lab
      • Contact: Michelle Kapolowicz, PhD; Phone Number: 949-824-9107; Email: mkapolow@hs.uci.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• between 18 and 85 years of age
• non-smokers with a score of 0-2 out of 10 maximum on the Fagerström index of smoking dependency
• cognitive performance within two standard deviations of the CERAD mean

Exclusion Criteria:

• less than 18 or greater than 85 years of age
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotine gum; Nicotine (6 mg) will be administered in the form of polacrilex gum that is available as an over-the-counter medication	Other: Nicotine gum; Nicotine (6 mg) will be administered in the form of polacrilex gum that is available as an over-the-counter medication
Placebo Comparator: Placebo gum; The placebo will also be a commercially available gum that resembles the nicotine gum in flavor, size, shape, color, and texture.	Other: Placebo gum; The placebo will also be a commercially available gum that resembles the nicotine gum in flavor, size, shape, color, and texture.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hearing thresholds	Hearing thresholds in dB SPL will be measured as a function of sound frequency from 125 Hz to 8000 Hz in quiet or in noise.	1 hour
Modulation detection	Amplitude-modulated sounds will be presented at 70 dB SPL or a comfortable level. The detection threshold in percent modulation depth (m= 0 to 100) will be recorded and converted into signal-to-noise ratios in dB (=20log(m)).	1 hour
Envelope following responses	Electrophysiological responses will be recorded in response to amplitude or frequency-modulated sounds. The sounds will be presented at 70 dB SPL or a comfortable level. The EEG signal strength that is in synchrony with the modulation frequency in micro-Volts will be recorded.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Pulse rate in pulses per minute will be measured via pulse oximetry.	10 minutes
Mood change	Mood change will be measured by a 9-category rating scale including: energy, contentedness, focus, relaxation, calmness, alertness, hunger etc.	10 minutes
Nicotine side effects	Side effects will be rated on a 5-point scale including: 1 = none (no symptoms at all); 2 = mild (slight jitters); 3 = moderate (jittery, slight dull headache); 4 = moderately severe (jittery, dull headache, mild nausea); 5 = severe (jittery, dull or pounding headache, nausea, vomiting).	10 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognition	Word learning, recall and animal fluency tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) will be measured and normalized to the national standard distribution, with a score of 0 equaling to the mean and 1 being one standard deviation above the mean performance.	1 hour

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Fan-Gang Zeng, PhD, University of California, Irvine

Publications and helpful links

General Publications

• Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. doi: 10.1111/j.1360-0443.1991.tb01879.x.
• Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989 Sep;39(9):1159-65. doi: 10.1212/wnl.39.9.1159.
• Pham CQ, Kapolowicz MR, Metherate R, Zeng FG. Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers. Psychopharmacology (Berl). 2020 Mar;237(3):833-840. doi: 10.1007/s00213-019-05421-x. Epub 2019 Dec 12.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): January 31, 2026
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: biomarker; nicotine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: HS#2013-9964; 1R01AG067073 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No