Using Nicotine to Reverse Age-related Auditory Processing Deficits

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Auditory Perceptual Impairment, Aging

Intervention / Treatment
-----------------
* Other: Nicotine gum
* Other: Placebo gum


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The nicotine and placebo gums will be administered in randomized, double-blind, counterbalanced fashion.
Masking: Double


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nicotine, biomarker