Nicotine Gum for Aging-Related Hearing Improvement

Overseen By Michael A Silver, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Berkeley

Must not be taking: Prescription medications

Disqualifiers: Hearing loss, Smoking, Psychiatric illness, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Nicotine enhances auditory-cognitive function because it mimics the brain's system for "paying attention" to important sounds amid distractions (for example, understanding speech in a noisy environment). In part, nicotine does this by activating inhibitory neurons in the auditory cortex. Since age-related hearing deficits result, in part, from the loss of inhibitory neurons in auditory cortex, this project will determine whether nicotine's effects can compensate for reduced inhibition in the aging auditory cortex and thereby restore auditory function. The investigators will use functional magnetic resonance imaging (fMRI) to measure the selectivity of responses in auditory cortex to tones of various frequencies. The investigators will measure the effects of nicotine (administered as chewing gum) and aging on these fMRI response properties. The investigators hypothesize that frequency selectivity will decrease with aging and increase following nicotine administration.

Do I have to stop taking my current medications?

Yes, you must stop taking regular prescription medications, except for oral contraceptives, to participate in this trial.

What safety data exists for nicotine gum used for hearing improvement?

The safety of nicotine gum, also known as nicotine polacrilex, has been evaluated in various studies primarily focused on smoking cessation. The Lung Health Study assessed cardiovascular conditions and other side effects in 3,094 participants using 2 mg nicotine polacrilex gum. Major adverse effects of nicotine polacrilex are very rare, and it is considered safer than smoking as it does not expose users to tar and carbon monoxide. The safety of nicotine preparations depends on factors like population, formulation, dose, and duration of use. While nicotine influences risk factors for certain diseases, it has not been well demonstrated to cause or aggravate them. Overall, nicotine gum is generally considered safe for use in smoking cessation, but specific safety data for its use in hearing improvement is not directly available from these studies. ^{1 2 3 4 5}

Is nicotine gum a promising drug for improving hearing in aging?

The research articles focus on nicotine gum as a tool for helping people quit smoking, not for improving hearing. They highlight its effectiveness in reducing smoking habits by replacing the nicotine from cigarettes with a safer form. However, they do not provide evidence that nicotine gum can improve hearing in aging individuals. ^{2 3 4 6 7}

What data supports the idea that Nicotine Gum for Aging-Related Hearing Improvement is an effective treatment?

The available research does not provide any data supporting the effectiveness of Nicotine Gum for Aging-Related Hearing Improvement. The studies focus on nicotine gum as a treatment for smoking cessation, not for hearing improvement. Therefore, there is no evidence from the provided information that nicotine gum is effective for improving hearing related to aging. ^{2 3 4 6 7}

Research Team

Michael A Silver, PhD

Principal Investigator

University of California, Berkeley

Eligibility Criteria

This trial is for aging adults who are non-smokers or very light smokers, as indicated by a low score on the Fagerström index. Participants should not have significant hearing loss, regular prescription medication use (except oral contraceptives), drug dependency, smoking habits above a minimal level, or a history of serious psychiatric, neurological conditions, diabetes, kidney failure or heart disease.

Inclusion Criteria

Non-smokers with a score of 0-2 out of 10 maximum on the Fagerström index of smoking dependency

Exclusion Criteria

History of psychiatric illness

I have had kidney failure in the past.

I regularly take prescription medications, not including birth control pills.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nicotine or placebo gum before fMRI measurements to assess auditory-cognitive function

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotine gum
• Placebo gum

Trial Overview The study tests whether nicotine gum can improve auditory function in older adults by enhancing their ability to focus on sounds amidst noise. It compares the effects of nicotine gum to placebo gum using fMRI scans to observe changes in how the brain's auditory cortex responds to different sound frequencies.

Participant Groups

Group I: Young (18-28 years) participants - nicotine gum Experimental Treatment 1 Intervention

6 mg nicotine gum, one time before fMRI measurements

Group II: Old (60-85 years) participants - nicotine gum Experimental Treatment 1 Intervention

6 mg nicotine gum, one time before fMRI measurements

Group III: Young (18-28 years) participants - placebo gum Placebo Group 1 Intervention

placebo gum, one time before fMRI measurements

Group IV: Old (60-85 years) participants - placebo gum Placebo Group 1 Intervention

placebo gum, one time before fMRI measurements

Nicotine gum is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Nicotine gum for:

• Smoking cessation

Approved in European Union as Nicotine gum for:

• Smoking cessation

Approved in Canada as Nicotine gum for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of California, Berkeley

Lead Sponsor

Trials

193

Recruited

716,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

The nicotine nasal spray (Nicotrol NS) produced significant hemodynamic changes, such as a notable increase in systolic blood pressure shortly after administration, indicating its rapid absorption and potential effectiveness compared to other forms of nicotine replacement therapy.

Despite the hemodynamic changes, pulmonary function remained unaffected by a single dose of nicotine, suggesting that while the nasal spray impacts cardiovascular parameters, it does not impair respiratory function in healthy nonsmokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamic effects of nicotine nasal spray devices on cardiovascular and pulmonary function. Fishbein, L., O'Brien, P., Hutson, A., et al.[2015]

In a clinical trial with 1818 smokers, the nicotine polacrilex lozenge demonstrated significant efficacy for smoking cessation, achieving 28-day abstinence rates of 46.0% for the 2-mg dose and 48.7% for the 4-mg dose compared to much lower rates in placebo groups.

The lozenge not only helped smokers quit but also reduced cravings and withdrawal symptoms, with most side effects being moderate and similar to those experienced with nicotine gum, indicating it is a safe option for both low- and high-dependence smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a nicotine lozenge for smoking cessation. Shiffman, S., Dresler, CM., Hajek, P., et al.[2022]

In a study of 314 daily smokers, starting nicotine polacrilex gum treatment 4 weeks before the quit date did not significantly improve smoking abstinence rates compared to starting on the quit date.

Both groups showed similar self-reported and biochemically verified abstinence rates after 12 months, indicating that the timing of nicotine gum initiation may not impact long-term quitting success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine gum treatment before smoking cessation: a randomized trial. Etter, JF., Huguelet, P., Perneger, TV., et al.[2018]

In a 5-year study involving 3923 ex-smokers, those using 2 mg nicotine polacrilex gum (NG) had salivary cotinine levels similar to current smokers, indicating significant nicotine replacement over the long term.

Despite NG users achieving cotinine levels comparable to smokers, the exact mechanism behind this nicotine replacement remains unclear, suggesting further research is needed to understand how NG affects nicotine metabolism in ex-smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levels of cotinine associated with long-term ad-libitum nicotine polacrilex use in a clinical trial. Murray, RP., Nides, MA., Istvan, JA., et al.[2019]

Nicotine gum, which binds nicotine to a polacrilex, is an effective method for treating tobacco dependence by transferring nicotine dependence from cigarettes to a safer form, reducing the risk of relapse.

The effectiveness of nicotine gum can be influenced by factors such as the dose, dosing schedule, and how vigorously it is chewed, highlighting the importance of proper administration for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic effects of nicotine polacrilex. Nemeth-Coslett, R.[2019]

In a study involving 5,887 adult smokers with early COPD, the use of nicotine polacrilex (NP) was found to be safe, with no significant association between NP use and increased rates of cardiovascular conditions or deaths over 5 years.

While about 25% of NP users reported minor and transient side effects, such as headache and mouth irritation, intensive instruction and monitoring during the smoking cessation program were linked to lower rates of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Lung Health Study Research Group. Murray, RP., Bailey, WC., Daniels, K., et al.[2019]

Nicotine replacement therapies, such as nicotine polacrilex and transdermal patches, are generally safe with very rare major adverse effects, making them a viable option for smoking cessation.

These therapies can double long-term abstinence rates, particularly benefiting highly dependent smokers, and produce lower nicotine levels than cigarettes without harmful tar and carbon monoxide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-benefit assessment of nicotine preparations in smoking cessation. Hughes, JR.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamic effects of nicotine nasal spray devices on cardiovascular and pulmonary function. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of a nicotine lozenge for smoking cessation. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Nicotine gum treatment before smoking cessation: a randomized trial. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Levels of cotinine associated with long-term ad-libitum nicotine polacrilex use in a clinical trial. [2019]

5. France pubmed.ncbi.nlm.nih.gov

Physiologic effects of nicotine polacrilex. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Lung Health Study Research Group. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Risk-benefit assessment of nicotine preparations in smoking cessation. [2020]