Actively Recruiting

Phase 2
Age: 60Years +
All Genders
NCT05746273

Depressed Mood Improvement Through Nicotine Dosing 3

Led by Vanderbilt University Medical Center · Updated on 2026-02-06

60

Participants Needed

1

Research Sites

180 weeks

Total Duration

On this page

Sponsors

V

Vanderbilt University Medical Center

Lead Sponsor

N

National Institute of Mental Health (NIMH)

Collaborating Sponsor

AI-Summary

What this Trial Is About

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 blinded study will expand past open-label trials supporting potential benefit in LLD. It will examine TDN's effect on depression severity and cognitive control functions measured by neuropsychological testing. The study will evaluate 60 eligible and enrolled participants over a 3-year period.

CONDITIONS

Official Title

Depressed Mood Improvement Through Nicotine Dosing 3

Who Can Participate

Age: 60Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 60 years or older
  • Diagnosis of major depressive disorder, single or recurrent episode (DSM-5 criteria)
  • On a stable therapeutic dose of an allowed SSRI or SNRI antidepressant for at least 6 weeks
  • Mild or greater active depression symptoms with MADRS score of 15 or higher
  • Cognition score of 24 or higher on the Mini-Mental State Examination (MMSE)
  • Fluent in English
Not Eligible

You will not qualify if you...

  • Presence of other Axis I psychiatric disorders except generalized anxiety disorder or social phobia symptoms during a depressive episode or ADHD diagnosis
  • Use of other augmentation medications for depression or ADHD, except short-acting sedatives
  • Use of tobacco or nicotine within the past year
  • Living with a smoker or regular exposure to secondhand smoke
  • History of moderate or severe alcohol or substance use disorder in the past 12 months
  • Acute suicidality
  • Acute grief within the last month
  • Current or past psychosis
  • Primary central nervous system neurological disorders such as dementia, stroke, or epilepsy
  • Unstable medical illness requiring urgent treatment
  • Contraindications to MRI
  • Electroconvulsive therapy or transcranial magnetic stimulation within the last 2 months
  • Current or planned psychotherapy that cannot be paused during the study
  • Allergy or hypersensitivity to nicotine patches
  • Regular use in the last 4 weeks of drugs with central cholinergic or anticholinergic effects or moderate/severe CYP2A6 inhibitors or inducers

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

Vanderbilt Psychiatric Hosptial

Nashville, Tennessee, United States, 37212

Actively Recruiting

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Research Team

P

Patricia Andrews, MD

CONTACT

C

Carrie Williams

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

TRIPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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