Open Label Extension Study of Depressed Mood Improvement Through Nicotine Dosing-3 (Depressed MIND3)

• Status: Not yet recruiting
• Trial end date: 2026-10-31
• Target enrollment: 0
• Participant gender: All

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 whol 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Collaborator: National Institute of Mental Health (NIMH)
• Treatments: Nicotine

Criteria

Only individuals who complete 12 weeks of the blinded Depressed MIND trial will be eligible for enrollment.

Eligibility criteria for the blinded phase includes:

Inclusion Criteria:

1. Age ≥ 60 years;

2. Diagnosis of major depressive disorder, single or recurrent episode (DSM5);

3. On a stable therapeutic dose of an allowed SSRI or SNRI for at least 8 weeks;

4. Severity: Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 15;

5. Cognition: Mini-Mental State Examination (MMSE) score ≥ 24;

6. Fluent in English

Exclusion Criteria:

1. Other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) symptoms occurring in a depressive episode;

2. Use of other medications for depression, e.g., bupropion or augmenting agents, although short-acting sedatives are allowed (see below);

3. Any use of tobacco or nicotine in the last year;

4. Living with a smoker or regular exposure to secondhand smoke;

5. History of alcohol use disorder or substance use disorder of moderate or greater severity (endorsing 4 or more of the 12 criteria) in the last 12 months;

6. Acute suicidality;

7. Acute grief (<1 month);

8. Current or past psychosis;

9. Primary neurological disorder, including dementia, stroke, epilepsy, etc.;

10. MRI contraindication;

11. Electroconvulsive therapy or transcranial magnetic stimulation in last 2 months;

12. Current or planned psychotherapy;

13. Allergy or hypersensitivity to nicotine patches;

14. In the last 4 weeks, regular use of drugs with central cholinergic or anticholinergic properties or moderate / severe CYP2A6 inhibitors /inducers.