Tinnitus, Chronic Subjective Tinnitus
Conditions
Keywords
Tinnitus, Nicotine, P300, EEG, Auditory oddball, Nicotinic acetylcholine receptor
Brief summary
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.
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'.
Interventions
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.
OTHERPlacebo gum
Flavor-matched sugar-free mint gum (Trident) matched to the nicotine gum in shape, flavor, color, and texture, chewed under the identical protocol.
Sponsors
Xianhui Wang
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants and the assessors who administer and score the outcome measures are masked to session assignment. Masking is supported by a flavor-, color-, shape-, and texture-matched placebo gum, independent gum preparation, and a blindfold during administration.
Intervention model description
Single-dose, two-period crossover: each participant receives a single 4 mg dose of nicotine polacrilex gum in one session and a flavor-matched placebo gum in the other, in randomized order, with at least 72 hours between sessions.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Auditory oddball P3 amplitude after administration (nicotine vs placebo) | Up to 2 hours after gum administration | 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. |
| Auditory oddball P3 latency after administration (nicotine vs placebo) | Up to 2 hours after gum administration | 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. |
| Auditory oddball target-detection accuracy after administration (nicotine vs placebo) | Up to 2 hours after gum administration | 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. |
| Auditory oddball reaction time after administration (nicotine vs placebo) | Up to 2 hours after gum administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting-state EEG spectral power and aperiodic (1/f) slope after administration (nicotine vs placebo) | Up to 2 hours after gum administration | 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. |
| Auditory oddball sensitivity (d') after administration (nicotine vs placebo) | Up to 2 hours after gum administration | 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. |
Countries
United States
Contacts
CONTACTXianhui Wang
PRINCIPAL_INVESTIGATORXianhui Wang
San Diego State University
Outcome results
None listed