Overseen ByWarren D Taylor
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Vanderbilt University Medical Center
No Placebo Group
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?Deficits in cognitive control are core features of late-life depression (LLD), contributing both to emotion dysregulation and problems with inhibiting irrelevant information, conflict detection, and working memory. Clinically characterized as executive dysfunction, these deficits are associated with poor response to antidepressants and higher levels of disability. Improvement of cognitive control network (CCN) dysfunction may benefit both mood and cognitive performance, however no current pharmacotherapy improves Cognitive Control Network deficits in LLD.
The study examines the hypothesis that nicotine acetylcholine receptor agonists enhance Cognitive Control Network function. This effect may resultantly improve mood and cognitive performance in LLD. Small, open-label studies of transdermal nicotine (TDN) patches have supported potential clinical benefit and provided support that transdermal nicotine administration engages the Cognitive Control Network.
This is an open-label, extension to the blinded Depressed MIND 3 (Depressed Mood Improvement through nicotine dosing) study. It will evaluate longer-term safety and efficacy of Transdermal Nicotine Patches for potential benefit in cognitive and depression outcomes in elderly depressed participants. Subjects complete blinded randomized trial of Depressed MIND-3 will be eligible for continuation in this extension. This extension study will consist of up to 12 weeks of treatment and a 3 -week safety follow-up period.
How does the nicotine patch treatment for depression differ from other treatments?
The nicotine patch is unique for depression treatment because it delivers nicotine through the skin, which may improve mood and increase REM sleep in depressed patients, unlike traditional antidepressants that are usually taken orally and work through different mechanisms.
12578Is the nicotine patch safe for use in humans?
The nicotine patch is generally considered safe for helping people quit smoking, but it can cause skin reactions like irritation or allergies in some users. Physical activity might affect how much nicotine is released, potentially leading to high levels in the blood, which could cause serious side effects.
346910Will I have to stop taking my current medications?
The trial requires participants to be on a stable dose of an allowed SSRI or SNRI for at least 8 weeks, so you can continue those medications. However, you cannot use other medications for depression or ADHD that you do not want to stop, except for short-acting sedatives.
Eligibility Criteria
This trial is for people aged 60 or older with major depressive disorder, who have been on a stable dose of certain antidepressants for at least 8 weeks. They must score ≥15 on the MADRS and ≥24 on the MMSE, speak English fluently, and not use tobacco or nicotine in the past year. Exclusions include substance abuse disorders, recent acute grief, other psychiatric disorders except GAD within depression, MRI contraindications, allergy to nicotine patches, and living with smokers.Participant Groups
The study tests if Transdermal Nicotine Patches can improve mood and cognitive performance in elderly individuals with depression by enhancing Cognitive Control Network function. It's an open-label extension of a previous blinded study where participants will receive up to 12 weeks of treatment followed by a safety follow-up.
1Treatment groups
Experimental Treatment
Group I: Transdermal Nicotine PatchExperimental Treatment1 Intervention
Participants will wear nicotine transdermal patches daily for 12-15 weeks. Participants will apply a study patch each morning and remove at bedtime. Active dose will titrate up from 3.5mg to 7mg, and then can optionally be further titrated to a maximum dose of 14mg. After week12, the dose will be slowly tapered over 2-3 weeks.
Transdermal Nicotine Patch is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Nicotine Patch for:
- Smoking cessation
🇪🇺 Approved in European Union as Nicotine Patch for:
- Smoking cessation
🇨🇦 Approved in Canada as Nicotine Patch for:
- Smoking cessation
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Vanderbilt Psychiatric HospitalNashville, TN
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Who is running the clinical trial?
Vanderbilt University Medical CenterLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
[Effects of transdermal nicotine as an adjunct in smoking cessation therapy. A double-blind randomized study controlled with placebo]. [2015]To assess the smoking cessation efficacy of transdermal nicotine patches an adjunct to low-intervention therapy, we conducted a double-blind, placebo-controlled trial in 158 smokers. Participants were randomly assigned to one of the following three study regimens that required daily application of two 15-cm2 patches: 1) 24-hour nicotine delivery, 2) nicotine delivery during wakeful hours only, and 3) placebo. The impact of the three regimens on smoking cessation rates and tobacco withdrawal symptoms was examined. During the last 2 weeks of the trial, 39% of the 24-hour nicotine regimen delivery group, 35% of those on wakeful hour nicotine regimens, and 13.5% of the placebo treatment group achieved abstinence. Self-reported quit rates for the two nicotine patch-wearing regimens, as compared with that for the placebo group, continued to be significantly higher at 6 months. Moreover, compared with placebo, the transdermal nicotine patches significantly reduced tobacco withdrawal symptoms during the first few weeks of quitting. The differences in quit rates and tobacco withdrawal symptoms between the to active groups were not statistically significant. The patches were well tolerated both topically and systemically. We concluded that transdermal nicotine, when used as an adjunct to low-intervention therapy, significantly reduced tobacco withdrawal symptoms and enhanced smoking cessation rates.
Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. [2018]Transdermal nicotine delivery systems are a cigarette smoking cessation aid designed to deliver nicotine into the systemic circulation via the skin. The partial replacement of plasma nicotine, which would have otherwise been obtained from cigarettes, reduces the severity of nicotine withdrawal symptoms, and so allows the smoker to abstain from smoking more easily. The systems are available in 16- and 24-hour application regimens, and are recommended for daily use for up to 20 weeks, including a series of 'weaning-off' courses. Clinical trials have shown that abstinence rates of 30 to 41% can be achieved during the first 6 weeks of application of transdermal nicotine systems, compared with 4 to 21% with placebo systems. The use of concomitant behavioural therapy may increase the success of treatment, with initial abstinence rates of up to 86% reported. However, long term abstinence rates (greater than 6 months) are considerably lower with or without behavioural therapy, often falling to less than half of the initial rates. Transdermal nicotine systems have been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse event. Mild gastric, central nervous system (CNS) and sleep disturbances have also been reported. The ease of use and unobtrusive nature of the systems have resulted in a high degree of patient compliance. Thus, transdermal nicotine systems offer a convenient form of nicotine replacement therapy which are well tolerated and, due to their pharmacokinetic profile, probably have a low dependency potential. The short term abstinence rates achieved with this therapy are encouraging; however, the maintenance of abstinence in the long term is harder to achieve. Transdermal nicotine replacement therapy, therefore, represents an important advance in the difficult area of smoking cessation management.
Clinical evaluation of the contact sensitization potential of a transdermal nicotine system (Nicoderm) [2015]Transdermal nicotine therapy has shown promise as a smoking cessation aid, but questions about its contact sensitization potential and long-term topical safety have been raised. The purpose of this study was to determine the contact sensitization potential of one nicotine transdermal system (Nicoderm, Marion Merrell Dow Inc, Kansas City, Mo, and ALZA Corporation, Palo Alto, Calif) in a population who were allowed to continue smoking.
Adverse skin reactions to nicotine in a transdermal therapeutic system. [2019]Nicotine in a transdermal therapeutic system (TTS) has been introduced recently to help people to stop smoking. 14 volunteers (10 male, 4 female) with a history of former adverse skin reactions to this device were investigated. Skin tests for contact urticaria and patch tests for contact allergy were done with the individual components of the TTS. Contact sensitization to nicotine was identified in 5 and to the TTS itself in 1 individual. Irritant reactions due to occlusion were present in 9 subjects. The optimal test agent and concentration for elucidating the adverse skin reaction was an aqueous solution of 10% nicotine base. Atopy, as diagnosed by history and skin prick tests to common inhalant allergens, and contact sensitization to standard patch test allergens, were each identified in 6 subjects. Nicotine should be added to the expanding list of transdermally delivered drugs which may elicit contact dermatitis.
Nicotine patch use in the general population: results from the 1993 California Tobacco Survey. [2019]Evidence from controlled clinical trials indicates that use of a transdermal nicotine patch improves abstinence rates up to a year after initial smoking cessation. Whether these results can be generalized to the general population has not been extensively investigated.
The pros and cons of transdermal nicotine therapy. [2015]To review current knowledge of the efficacy, safety and cost of transdermal nicotine therapy for smoking cessation.
Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. [2019]The role of nicotine as an indirect cholinergic agent in sleep has been studied in normal subjects. There are no studies of its effects on sleep in depressed patients. Nicotine transdermal patches (17.5 mg), were studied in eight depressed patients (DSM-III-R) and eight normal volunteers. Subjects wore placebo and nicotine patches for 24 h. Depressed patients showed increased REM sleep without changes in other sleep variables. They also showed a short term improvement of mood. Normal volunteers had sleep fragmentation, and reduction of REM sleep time. No major side effects were reported in either group.
The effects of transdermal nicotine therapy for smoking cessation on depressive symptoms in patients with major depression. [2015]This study examines the effects of transdermal nicotine patches for smoking cessation on depressive and withdrawal symptoms among 38 non-medicated subjects with Major Depressive Disorder. The study was conducted over a 29-day period, which included a 7 day baseline phase, a 14 day treatment phase, and an 8 day placebo phase. During the treatment phase subjects received either active nicotine patches (N = 18) or placebo patches (N = 20) that were administered in a randomized, double-blind fashion. The target quit date (TQD) was day 8. Significantly, more subjects in the placebo group than in the nicotine group resumed smoking following the TQD (50% vs. 22%). There was little evidence for effects of active nicotine patches on measures of mood (HRSD, BDI, POMS) or withdrawal symptoms among subjects that remained abstinent throughout the study (N = 24). Those who resumed smoking had more severe withdrawal symptoms than those who remained abstinent. One patient in the placebo group (n = 20) became more depressed after 2 weeks of abstinence. None of the patients in the nicotine group (n = 18) became more depressed.
Effect of exercise on transdermal nicotine release in healthy habitual smokers. [2019]Transdermal nicotine patches have become a frequently prescribed tool in smoking cessation programs during the past years. However, there is circumstantial evidence that transdermal nicotine release substantially varies with physical activity producing toxic plasma concentrations that may account for severe adverse events.
Reasons for non-adherence to nicotine patch therapy during the first month of a quit attempt. [2022]Prior research has shown that the transdermal nicotine patch is a safe and effective aid to smoking cessation, but adherence to the directed use of the nicotine patch is often low. Few studies have examined participant-reported reasons for non-adherence to nicotine patch therapy during a quit attempt.