Acute Nicotine Gum and Auditory Brain Responses in Adults With Chronic Tinnitus

A Randomized, Double-Blind, Placebo-Controlled, Within-Subject Crossover Trial of a Single 4 mg Dose of Nicotine Polacrilex Gum on Auditory Oddball P3, Oddball Task Performance, and Resting-State EEG in Non-Smoking Adults With Chronic Tinnitus

This study tests whether a single dose of nicotine gum changes brain responses to sounds and the ability to detect target sounds in non-smoking adults with chronic tinnitus. In a double-blind, placebo-controlled, within-subject crossover design, each participant attends two sessions and receives a single 4 mg dose of nicotine polacrilex gum at one session and a flavor-matched placebo gum at the other, in random order. After gum administration, EEG is recorded at rest and during an active auditory oddball task. The primary measures are the P3 brain response (amplitude and latency) and oddball task accuracy and reaction time.

Study Overview

• Status: Not yet recruiting
• Conditions: Tinnitus; Chronic Subjective Tinnitus
• Intervention / Treatment: Drug: Nicotine polacrilex gum 4 mg; Other: Placebo gum

Detailed Description

Relationship to prior registration: This trial is a separate, newly enrolled study conducted under the same IRB-approved protocol (San Diego State University IRB-25-0430) as the completed trial NCT07772089, which evaluated acute nicotine gum effects on tinnitus loudness and selective attention. Participants and data in this trial are collected independently of NCT07772089.

Population: Non-smoking adults aged 18-80 years with chronic subjective tinnitus, using the same eligibility criteria as NCT07772089.

Intervention and administration: A single 4 mg dose of nicotine polacrilex gum or flavor-matched placebo gum, chewed continuously for 20 minutes at one chew per second (paced by a 1 Hz auditory cue) with saliva retained, following the administration protocol established in the investigators' gum optimization study.

Design: Randomized, double-blind, placebo-controlled, within-subject crossover with two sessions on separate days separated by a washout of at least 72 hours. Session order is randomized 1:1 using a computer-generated sequence; allocation is concealed with sequentially numbered, opaque, sealed envelopes; gum is prepared by an independent examiner and participants are blindfolded during administration.

Procedures: At the start of the first session, pure-tone audiometry, the Tinnitus Handicap Inventory, the Tinnitus Functional Index, and a pre-administration tinnitus loudness match are completed. In each session, tinnitus loudness is matched before and after gum administration. All EEG and oddball measures are obtained after gum administration only. EEG is analyzed at electrodes Fz, Cz, Pz, and Oz: resting-state spectral power (delta, theta, alpha, beta, gamma) and aperiodic (1/f) slope, and P3 amplitude and latency to target tones in an active auditory oddball task, with concurrent behavioral accuracy, reaction time, and d'.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xianhui Wang; Phone Number: 619-594-1151; Email: kwang5@sdsu.edu

Study Locations

• United States
  • California
    • San Diego, California, United States, 92182
      • San Diego State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Non-smoking adult, defined as fewer than 100 cigarettes in a lifetime and none in the past year, with a Fagerstrom Test for Nicotine Dependence score of 2 or less and a negative urinary cotinine test
• Chronic subjective tinnitus of at least 6 months' duration

Exclusion Criteria:

• Current or recent tobacco or nicotine use
• Pregnancy or breastfeeding
• Unstable cardiovascular disease
• Any condition precluding the psychoacoustic tasks

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 (4 mg); Single 4 mg dose of nicotine polacrilex gum, chewed for 20 minutes at 1 Hz using the standardized administration protocol.	Drug: Nicotine polacrilex gum 4 mg; A single 4 mg dose (one 4 mg piece) of mint nicotine polacrilex gum, chewed continuously for 20 minutes at one chew per second with saliva retained.; Other Names: Nicorette
Placebo Comparator: Placebo gum; Flavor-, color-, shape-, and texture-matched placebo gum, chewed under the identical protocol.	Other: Placebo gum; Flavor-matched sugar-free mint gum (Trident) matched to the nicotine gum in shape, flavor, color, and texture, chewed under the identical protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Auditory oddball P3 amplitude after administration (nicotine vs placebo)	P3 (P300) peak amplitude in microvolts was measured from the event-related potential elicited by target tones during an active auditory oddball task performed after gum administration, at electrodes Fz, Cz, Pz, and Oz. Amplitude was compared between the nicotine and placebo sessions.	Up to 2 hours after gum administration
Auditory oddball P3 latency after administration (nicotine vs placebo)	P3 (P300) peak latency in milliseconds was measured from the event-related potential elicited by target tones during an active auditory oddball task performed after gum administration, at electrodes Fz, Cz, Pz, and Oz. Latency was compared between the nicotine and placebo sessions.	Up to 2 hours after gum administration
Auditory oddball target-detection accuracy after administration (nicotine vs placebo)	Behavioral accuracy (percentage of target tones correctly detected) in the active auditory oddball task performed after gum administration was compared between the nicotine and placebo sessions.	Up to 2 hours after gum administration
Auditory oddball reaction time after administration (nicotine vs placebo)	Mean reaction time in milliseconds to correctly detected target tones in the active auditory oddball task performed after gum administration was compared between the nicotine and placebo sessions.	Up to 2 hours after gum administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting-state EEG spectral power and aperiodic (1/f) slope after administration (nicotine vs placebo)	Resting-state EEG was recorded after gum administration. Absolute spectral power was computed for the delta, theta, alpha, beta, and gamma frequency bands, and the aperiodic (1/f) slope of the power spectrum was estimated, at electrodes Fz, Cz, Pz, and Oz. Values were compared between the nicotine and placebo sessions.	Up to 2 hours after gum administration
Auditory oddball sensitivity (d') after administration (nicotine vs placebo)	Signal-detection sensitivity (d') computed from hits and false alarms in the active auditory oddball task performed after gum administration was compared between the nicotine and placebo sessions.	Up to 2 hours after gum administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-session change in psychoacoustic tinnitus loudness match (nicotine vs placebo)	Tinnitus loudness was matched to the participant's tinnitus pitch by a method-of-adjustment procedure and expressed in dB sensation level. The pre-to-post change was compared between the nicotine and placebo sessions.	Baseline (pre-administration) and up to 2 hours after gum administration
Tinnitus Handicap Inventory (THI) score	The Tinnitus Handicap Inventory is a 25-item self-report questionnaire of tinnitus-related handicap. Each item is answered yes (4 points), sometimes (2 points), or no (0 points). The total score ranges from 0 to 100; higher scores indicate greater tinnitus handicap (a worse outcome).	Baseline (pre-administration, first session)
Tinnitus Functional Index (TFI) score	The Tinnitus Functional Index is a 25-item self-report questionnaire of the functional impact of tinnitus. Each item is rated on a 0-10 scale, and the overall score is the mean of the answered items multiplied by 10. The overall score ranges from 0 to 100; higher scores indicate more severe tinnitus impact (a worse outcome).	Baseline (pre-administration, first session)
Pure-tone audiometry (0.25-12 kHz)	Baseline hearing thresholds, collected once at the start of the first session.	Baseline (pre-administration, first session)

Collaborators and Investigators

• Sponsor: San Diego State University
• Investigators: Principal Investigator: Xianhui Wang, San Diego State University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: October 9, 2026
• First Submitted That Met QC Criteria: October 9, 2026
• First Posted (Actual): October 16, 2026

Study Record Updates

• Last Update Posted (Actual): November 6, 2026
• Last Update Submitted That Met QC Criteria: November 3, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: EEG; Tinnitus; Nicotine; P300; Nicotinic acetylcholine receptor; Auditory oddball
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Tinnitus; Therapeutics; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Carbohydrates; Polymers; Macromolecular Substances; Polysaccharides; Biopolymers; Plant Gums; Candy; Chewing Gum; Tobacco Use Cessation Devices; Nicotine Chewing Gum
• Other Study ID Numbers: IRB-25-0430-EEG

Drug and device information, study documents

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