NCT05746546

Depressed Mood Improvement Through Nicotine Dosing-3 (Depressed MIND3) Extension

Open Label Extension Study of Depressed Mood Improvement Through Nicotine (Depressed MIND3)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Vanderbilt University Medical Center · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The purpose of this open-label extension to the Depressed MIND 3 study will be to gather data on longer-term benefits and safety in patients with late-life depression (LLD). Neuronal nicotinic receptors have long been known to play a critical role in memory function in preclinical studies, with nicotine improving attention, learning, and memory function. This may be particularly relevant in LLD, which is characterized both by affective symptoms and broad cognitive deficits. The co-occurrence of cognitive deficits in LLD is a clinically relevant phenotype characterized by significant disability and poor antidepressant response. Cognitive deficits can persist even with successful antidepressant treatment and increase the risk of depression relapse. Despite the clinical importance of cognitive deficits in LLD, there are no established treatments that specifically target cognition in this population. The lack of clear pharmacologic targets and therapies aimed at improving cognitive deficits in depression is a substantial deficiency in current therapeutics. Investigators propose that modulation of the cognitive control network by stimulation of cholinergic system nicotinic acetylcholine receptors will improve both mood and cognition in depressed elders. The study is an open-label extension of a randomized double blind placebo control trial that will enroll 80 participants over a 3-year period. After randomization and completion of the blinded study phase, participants will be eligible for this 12-week extension. At the completion of Week-12 visit of the Depressed MIND -3, all eligible subjects will be offered enrollment in the open label extension study. Study visits during the treatment period for all subjects will occur approximately 3 weeks with flexible dose titration. This will be followed by a 1-3 week taper phase. The total duration of study participation will be approximately 15 weeks.

Conditions

• Depressive Disorder

Interventions

Type	Name	Description
DRUG	Transdermal Nicotine patch	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.

Timeline

• Start date: 2023-04-15
• Primary completion: 2026-10-31
• Completion: 2026-10-31
• First posted: 2023-02-27
• Last updated: 2026-02-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study