Tinnitus, Chronic Subjective Tinnitus
Conditions
Keywords
Tinnitus, Nicotine, Nicotinic acetylcholine receptor, Selective attention, Nicotine polacrilex gum
Brief summary
This study tested whether a single dose of nicotine gum can reduce the loudness of tinnitus (ringing in the ears) in non-smoking adults with chronic tinnitus. Nicotine acts on brain nicotinic acetylcholine receptors that regulate the balance of excitation and inhibition in auditory and attention networks, and may temporarily quiet the phantom sound while improving the ability to focus on relevant sounds. Using a double-blind, placebo-controlled, within-subject crossover design, each participant attended two sessions and received a single 4 mg dose of nicotine polacrilex gum at one session and a flavor-matched placebo gum at the other, in random order. The primary measure was the within-session change in a psychoacoustic match of tinnitus loudness; auditory selective attention was a secondary measure.
Detailed description
Background: Tinnitus is associated with excitatory-inhibitory imbalance across auditory, attentional, and limbic circuits. Nicotinic acetylcholine receptor modulation is a candidate dual-target mechanism, but it has not been evaluated for tinnitus in humans. Dose and protocol: The 4 mg dose and a standardized administration protocol (continuous chewing for 20 minutes at one chew per second, paced by a 1 Hz auditory cue, with saliva retained and spitting minimized to maximize buccal absorption) were established in a preceding gum optimization study in non-smokers. Trial design: Randomized, double-blind, placebo-controlled, within-subject crossover. Each participant attended two sessions on separate days, separated by a washout of at least 72 hours, receiving nicotine gum at one session and matched placebo gum at the other in randomized 1:1 order. Allocation was concealed with sequentially numbered, opaque, sealed envelopes; an independent examiner prepared the gum and participants wore a blindfold during administration. Outcomes: The primary outcome was the within-session change (post minus pre) in psychoacoustic tinnitus loudness match, compared between the nicotine and placebo sessions. The secondary outcome was the within-session change in auditory selective attention (Coordinate Response Measure percent correct). Additional pre-specified measures were pure-tone audiometry, the Tinnitus Handicap Inventory, and the Tinnitus Functional Index. Outcomes were analyzed with generalized linear mixed models.
Interventions
DRUGNicotine 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.
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
San Diego State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants and the assessors who administered the outcome measures were masked to session assignment. Masking was 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 received 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 |
|---|---|---|
| Within-session change in psychoacoustic tinnitus loudness match (nicotine vs placebo) | Baseline (pre-administration) and up to 2 hours after gum administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Auditory selective attention after administration (Coordinate Response Measure percent correct), nicotine vs placeb | Up to 2 hours after gum administration | Selective attention was assessed with the Coordinate Response Measure after gum administration and scored as the percentage of trials on which both the color and number were correctly identified; performance was compared between the nicotine and placebo sessions. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORXianhui Wang
San Diego State University
Outcome results
None listed