Phase 2 N=29 Basic Science

Depressed Mood Improvement Through Nicotine Dosing 2

Depressive Disorder

Bottom Line

View on ClinicalTrials.gov: NCT04433767 ↗

Enrolled (actual)

Serious AEs

3.5%

Results posted

Dec 2023

Primary outcome: Primary: MADRS (Montgomery Asberg Depression Rating Scale) Score Change — -15.4 units on a scale — p=< 0.001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Transdermal Nicotine patch (Drug)
Age: Adult, Older Adult · 60+ yrs
Sex: All
Sponsor: Vanderbilt University Medical Center
Primary completion: Oct 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY MADRS (Montgomery Asberg Depression Rating Scale) Score Change	-15.4	< 0.001 sig
PRIMARY Number of Participants Exhibiting Reduction in Frontal Activation During the Emotional Stroop Task During Functional Magnetic Resonance Imaging (MRI)	18; 16; 17; 10	—
SECONDARY NIH EXAMINER Test Battery Executive Composite Score Change	0.16	0.0127 sig
SECONDARY NIH EXAMINER Test Battery Cognitive Control Factor Change	0.29	0.0005 sig
SECONDARY NIH EXAMINER Test Battery Fluency Factor Change	0.18	0.1027
SECONDARY NIH EXAMINER Test Battery Working Memory Factor Change	0.05	0.4846
SECONDARY Choice Reaction Time (CRT) Performance Change	-0.67	0.7290
SECONDARY Selective Reminding Task Performance Change	0.33	0.9196
SECONDARY Trait Adjectives Task, Change in Positive Items Endorsed	2.28	0.033 sig
SECONDARY Trait Adjectives Task, Change in Negative Items Rejected	1.92	0.041 sig
SECONDARY Trait Adjectives Task, Change in Reaction Time to Endorse Positive Items	-120.99	0.001 sig
SECONDARY Trait Adjectives Task, Change in Reaction Time to Reject Negative Items	-149.20	0.001 sig
SECONDARY Ruminative Response Scale Score Change	-7.32	<0.001 sig
SECONDARY Apathy Evaluation Scale (AES) Score Change	-7.36	0.001 sig
SECONDARY Insomnia Severity Index Score Change	-4.50	<0.001 sig
SECONDARY Penn State Worry Questionnaire (PSWQ) Score Change	-5.07	0.183
SECONDARY Fatigue Severity Scale Score Change	-3.15	0.170
SECONDARY Dimensional Anhedonia Rating Scale (DARS) Score Change	4.63	0.051
SECONDARY General Anxiety Disorder-7 Item Scale (GAD7) Score Change	-2.38	<0.001 sig
SECONDARY Patient Reported Outcome Measurement Information System (PROMIS) Applied Cognition Abilities Short Form Score Change	5.15	0.002 sig
SECONDARY Attentional Control Scale Score Change	6.04	0.002 sig
SECONDARY Anxiety Sensitivity Index 3 (ASI-3) Score Change	-4.40	0.876

Summary

Deficits in cognitive control are core features of late-life depression, 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 CCN deficits in LLD. Supported by pilot data, Investigators propose that nicotine acetylcholine receptor agonists enhance CCN function and resultantly improve mood and cognitive performance in late-life depression. The objective of this initial R61-phase trial is to first determine whether transdermal nicotine enhances CCN neural activity in an exposure-dependent fashion during an emotional response inhibition task (the emotional Stroop task). Investigator's approach for the R61 phase is to examine in 36 older adults with Major Depressive Disorder whether transdermal nicotine patches enhance CCN activity over 12 weeks as measured during fMRI with the emotional Stroop task while measuring nicotine and nicotine metabolite levels. Transdermal nicotine has a mechanism of action that is distinct from current antidepressants, potentially making it a potentially important antidepressant augmentation agent. If hypotheses are correct, as patches are commercially available, this approach could be rapidly moved into definitive studies and may have applicability to other psychiatric disorders characterized by CCN dysfunction.

Eligibility Criteria

Inclusion Criteria

Age > 60 years;
Diagnosis of major depressive disorder, single or recurrent episode (DSM5);
On a stable therapeutic dose of an allowed selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for at least 8 weeks;
Severity: Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 15;
Cognition: Mini-Mental State Examination (MMSE) score ≥ 24;
Fluent in English

Exclusion Criteria

Other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) symptoms occurring in a depressive episode;
Use of other medications for depression, e.g., bupropion or augmenting agents, although short-acting sedatives are allowed (see below);
Any use of tobacco or nicotine in the last year;
Living with a smoker or regular exposure to secondhand smoke;
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;
Acute suicidality;
Acute grief (<1 month);
Current or past psychosis;
Primary neurological disorder, including dementia, stroke, epilepsy, etc.;
MRI contraindication;
Electroconvulsive therapy or transcranial magnetic stimulation in last 2 months;
Current or planned psychotherapy;
Allergy or hypersensitivity to nicotine patches;
In the last 4 weeks, regular use of drugs with central cholinergic or anticholinergic properties or moderate / severe CYP2A6 inhibitors /inducers.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04433767). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.