Depressed Mood Improvement Through Nicotine Dosing (Depressed MIND Study)

NCT02816138 | Completed Phase 4 Results

• 1 other identifier: DepMIND
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Late-life depression is characterized by both affective (mood) symptoms and cognitive deficits. There is currently no intervention that may provide consistent benefits to both mood and cognitive performance. Agonist activity at the nicotinic acetylcholine receptors via transdermal nicotine patches may provide benefit to both mood and cognition, working through nicotine's effects on brain neural networks, specifically the cognitive control network and default mode network. In this initial pilot project, the investigators will test this hypotheses in 15 nonsmoking depressed elders with subjective cognitive impairment. Following baseline neuroimaging and cognitive testing, participants will receive 12 weeks of open-label transdermal nicotine. Afterwards, participants will repeat neuroimaging and cognitive assessments.

Conditions

Major Depressive Disorder

Keywords

Geriatrics; Depression; Elderly; Cognition; Memory

Outcome Measures

Primary Outcomes (2)

• Change in Total MADRS (Montgomery Asberg Depression Rating Scale) Score

  Primary mood outcome measured by the total score of the clinician-rated MADRS. MADRS was measured every 3 weeks (baseline, week 3, week 6, week 9, and week 12). MADRS total score range is 0-60, where higher scores indicate greater depression severity.

  Baseline to week 12

• Change in Continuous Performance Task (CPT) Performance

  Primary cognitive outcome, the CPT is a neuropsychological test that measures attention. In this 14-minute test, participants are asked to respond when any letter appears, except the non-target letter "X". This test is conducted at baseline and at week 12. The specific primary outcome metric is standard error of change in the inter-stimulus hit reaction time, or variability between different trials. There is no absolute range, but lower scores indicate decreased variability across trials and overall better performance.

  Baseline to week 12

Secondary Outcomes (8)

• Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score

  Baseline to week 12

• Change in Penn State Worry Questionnaire (PSWQ)

  Baseline to week 12

• Change in Ruminative Response Scale Total Score

  Baseline to week 12

• Change in Apathy Evaluation Scale (AES)

  Baseline to 12 weeks

• Change in MFQ (Memory Frequency Questionnaire) Score

  Baseline to week 12

Study Arms (1)

Transdermal nicotine patch

EXPERIMENTAL

Transdermal nicotine patch, administered on awakening and removed at bedtime (16h/d). Dosing 3.5mg patch/daily, titrated over study to maximum dose of 21mg patch/daily.

Drug: Nicotine

Interventions

Nicotine DRUG

Open-label transdermal nicotine patch

Also known as: Nicotrol, Nicoderm CQ

Transdermal nicotine patch

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 60 years;
• DSM-5 (Diagnostic and statistical manual-5) diagnosis of major depressive disorder, single or recurrent episode;
• Subjective cognitive decline, defined as endorsing 20% of items on the Cognitive Complaint Index (CCI);
• depression severity: MADRS (Montgomery-Asberg Depression Rating Scale) ≥ 15;
• cognition: MOCA (Montreal Cognitive Assessment) ≥ 24;
• fluent in English;
• intact hearing / vision allowing completion of study procedures;
• for individuals on antidepressants at study entry, they must be on a stable dose for at least 6 weeks.

You may not qualify if:

• Other Axis I psychiatric disorders, except for anxiety symptoms occurring in a depressive episode;
• History of alcohol or drug dependence or abuse in the last 3 years;
• Tobacco or nicotine use in last year;
• History of a developmental disorder or IQ score \< 70;
• Acute suicidality;
• Acute grief (\<1 month);
• Current or past psychosis;
• Primary neurological disorder, including dementia, stroke, brain tumors, etc.;
• Any MRI contraindication;
• Unstable medical illness;
• Allergy or hypersensitivity to nicotine patches;
• Regular use of drugs with centrally acting cholinergic or anticholinergic properties in last 4 weeks, including acetylcholinesterase inhibitors;
• Current or planned psychotherapy;
• Electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) in last two months.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212, United States

Location

Related Publications (1)

• Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD. Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression. J Clin Psychiatry. 2018 Aug 28;79(5):18m12137. doi: 10.4088/JCP.18m12137.

  PMID: 30192444 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Nicotine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Open label trial design Only 8/14 participants who completed the study could tolerate the maximum patch dose of 21mg. The other 6 could only tolerate a maximum dose of 10.5mg, primarily due to adverse events.

Results Point of Contact

• Title: Warren D. Taylor, MD
• Organization: Vanderbilt University Medical Center

warren.d.taylor@vanderbilt.edu

6153221073

Study Officials

• Warren D Taylor, MD, MHSc

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: June 24, 2016
• First Posted: June 28, 2016
• Study Start: October 1, 2016
• Primary Completion: August 23, 2017
• Study Completion: September 12, 2017
• Last Updated: September 27, 2018
• Results First Posted: September 27, 2018

Record last verified: 2018-08

Locations

US (1)