Major Depressive DisorderPhase 4NCT02816138

Depressed Mood Improvement Through Nicotine Dosing (Depressed MIND Study)

A Phase 4 study testing Nicotine in people with Major Depressive Disorder, run by Vanderbilt University Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 60 years and older
Conditions the study is for: Major Depressive Disorder
What is being tested?: Nicotine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteUnited States
Study dates: Oct 2016to 12 Sep 2017
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 60 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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);

Show all 14Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt Psychiatric Hospital
Nashville, Tennessee, 37212

Other trials in United States

About this study

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.

Read the detailed description

Late-life depression (LLD) is characterized both by affective symptoms and 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 treatments that improve cognitive deficits in depression is a deficiency in current therapeutics.

Modulation of the cholinergic system by nicotinic receptor stimulation may improve both mood and cognition in depressed elders. Clinically, transdermal nicotine improves mood in smokers and a placebo-controlled pilot trial in nonsmoking adults found that transdermal nicotine significantly improved mood. In a previous trial examining Mild Cognitive Impairment, transdermal nicotine safely improved cognitive function on tests of attention, episodic memory, and processing speed. These same cognitive domains are impaired in LLD. The investigators hypothesize that these effects on mood and cognition are mediated through nicotine's effect to increase cognitive control network activity and reduce default mode network (DMN) activity. This pattern of network activity during tasks demanding external attention is associated with better task performance. Furthermore, as seen in smokers, nicotine's effect on these networks reduces depression's bias to negatively valenced stimuli and decreases rumination.

The central hypothesis is that in LLD, transdermal nicotine will safely improve depression by increasing activity in cognitive control regions and decreasing activity in DMN regions. This will result in a decreased attentional bias to and reactivity to negative stimuli. A secondary hypothesis is that transdermal nicotine will also improve subjective and objective cognitive performance through these same network effects.

Primary Aim 1: To determine whether administration of transdermal nicotine over 12 weeks improves clinical symptoms in patients with LLD with subjective cognitive impairment (SCI).

Hypothesis 1: Transdermal nicotine administration will result in reductions in depression severity measured by the Montgomery-Asberg Depression Rating Scale (MADRS; primary mood outcome). It will also result in improvement in broader assessments of depressive symptomatology, including anhedonia, apathy, fatigue, sleep, and rumination (secondary outcomes).

Hypothesis 2: Transdermal nicotine administration will result in improvements in attentional performance on the Conner's Continuous Performance Task (CPT; primary cognitive outcome). It will also result in improvement in subjective and objective cognitive performance on other tasks measuring attention, episodic memory, working memory, processing speed, and executive function (secondary outcomes).

Secondary Aim 2: To determine whether administration of transdermal nicotine over 12 weeks modulates canonical intrinsic functional network activity in LLD with SCI.

Hypothesis 3: On repeat administration of the Posner task of external attention, transdermal nicotine administration will result in increased activity within the cognitive control network and decreased activity within the default mode network.

Hypothesis 4: Transdermal nicotine administration will result in increased functional connectivity within the cognitive control network and decreased connectivity within the default mode network at rest.

Hypothesis 5: Changes in intrinsic network activity / connectivity with transdermal nicotine administration will be associated with changes in mood symptoms and subjective and objective cognitive performance.

Conditions: Major Depressive Disorder
Being tested: Nicotine
Keywords: Geriatrics, Depression, Elderly, Cognition, Memory
Medical subject headings: Depressive Disorder, Major, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NicotineDrug
Also called Nicotrol, Nicoderm CQ
Open-label transdermal nicotine patch

Study groups in NCT02816138
Study group	Role	What they receive
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. Receives: Drug: Nicotine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Baseline to week 12

Secondary outcomes (8)

Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score
Secondary mood outcome: Change in anhedonia measured by SHAPS, a self-report questionnaire that ranges from 0-42, where higher scores indicate greater anhedonia.
Measured: Baseline to week 12
Change in Penn State Worry Questionnaire (PSWQ)
Secondary mood outcome: Change in anxiety and worry measured by PSWQ, a self-report questionnaire with a range of 16-80, where higher scores indicate greater anxiety and worry.
Measured: Baseline to week 12
Change in Ruminative Response Scale Total Score
Secondary mood outcome: Change in rumination measured by the Ruminative Response Scale total score measured at baseline and week 12. This is a self-report scale with a range of 0-66, where higher scores indicate higher levels of rumination.
Measured: Baseline to week 12
Change in Apathy Evaluation Scale (AES)
Secondary Mood Outcomes: Change in apathy as measured by the self-report AES, a questionnaire with a range of 0-54, where lower scores indicate greater apathy.
Measured: Baseline to 12 weeks
Change in MFQ (Memory Frequency Questionnaire) Score
Secondary cognitive outcome: Change in subjective cognitive performance as measured by MFQ, a self-report scale ranging from 64-448. Higher scores indicate better subjective memory function, while lower scores indicate poorer subjective memory function.
Measured: Baseline to week 12
Change in Choice Reaction Time (CRT) Performance
Secondary cognitive outcome, a neuropsychological test measure of attention. We examined the total response time for the CRT. Lower scores indicate better performance.
Measured: Baseline to week 12
Change in One-back Test Performance
Secondary cognitive outcome examining change in speed of responses ton the one-back test, no absolute range. In this variant of the "N-back" task, participants view a series of cards, and indicate whether the card they are currently viewing is identical to the previously viewed card. Lower scores indicate better performance.
Measured: Baseline to week 12
Change in NYU (New York University) Paragraph Recall Performance
Secondary cognitive outcome of a neuropsychological test examining episodic memory performance using the NYU Paragraph Recall test. No absolute range. Higher scores indicate better performance.
Measured: Baseline to week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201612 Sep 2017

First posted28 Jun 2016 (estimated)
Study startOct 2016
Primary completion23 Aug 2017
Study completion12 Sep 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02816138
Sponsor's protocol ID: DepMIND
Status last verified: Aug 2018
First submitted: 24 Jun 2016
Last updated: 27 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Undecided

Publications

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.
PubMed 30192444

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 27 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Depressed Mood Improvement Through Nicotine Dosing (Depressed MIND Study)
ClinicalTrials.gov ID: NCT02816138
Acronym / sponsor ID: DepMIND
Conditions: Major Depressive Disorder
Keywords: Geriatrics, Depression, Elderly, Cognition, Memory
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Vanderbilt University Medical CenterUniversity, hospital or other
Study start: Oct 2016 (actual)
Primary completion: 23 Aug 2017 (actual)
Study completion: 12 Sep 2017 (actual)
First posted: 28 Jun 2016 (estimated)
Results: Posted 27 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Primary Aim 1: To determine whether administration of transdermal nicotine over 12 weeks improves clinical symptoms in patients with LLD with subjective cognitive impairment (SCI).

Secondary Aim 2: To determine whether administration of transdermal nicotine over 12 weeks modulates canonical intrinsic functional network activity in LLD with SCI.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Transdermal nicotine patch	Experimental	Drug: NicotineTransdermal 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.

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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;

Key exclusion criteria (14 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NicotineAlso: Nicotrol, Nicoderm CQOpen-label transdermal nicotine patch	Drug	Transdermal nicotine patch

Primary outcome

Change in Total MADRS (Montgomery Asberg Depression Rating Scale) Score
Time frame: Baseline to week 12
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.
Change in Continuous Performance Task (CPT) Performance
Time frame: Baseline to week 12
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.

8 secondary outcomes

Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score
Time frame: Baseline to week 12
Change in Penn State Worry Questionnaire (PSWQ)
Time frame: Baseline to week 12
Change in Ruminative Response Scale Total Score
Time frame: Baseline to week 12
Change in Apathy Evaluation Scale (AES)
Time frame: Baseline to 12 weeks
Change in MFQ (Memory Frequency Questionnaire) Score
Time frame: Baseline to week 12
Change in Choice Reaction Time (CRT) Performance
Time frame: Baseline to week 12
Change in One-back Test Performance
Time frame: Baseline to week 12
Change in NYU (New York University) Paragraph Recall Performance
Time frame: Baseline to week 12

Results and safety

Results posted to the registry on 27 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Transdermal Nicotine Patch	15	14

Primary outcome: Change in Total MADRS (Montgomery Asberg Depression Rating Scale) Score

Time frame: Baseline to week 12. Mean (Standard Deviation). Unit: units on a scale

Measure	Transdermal Nicotine Patch n = 15
Value	-18.45 (7.98)

Transdermal Nicotine Patch: p <0.001, Regression, Linear

Population analysed: Analyses included all participants, including the one subject who withdrew early. Missing values were imputed using the mean value of the sample at that time point.

Primary outcome: Change in Continuous Performance Task (CPT) Performance

Time frame: Baseline to week 12. Mean (Standard Deviation). Unit: milliseconds

Measure	Transdermal Nicotine Patch n = 14
Value	-0.003 (0.135)

Transdermal Nicotine Patch: p = 0.761, Wilcoxon (Mann-Whitney)

Population analysed: Subject who withdrew early not included due to no 12-week data.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Transdermal Nicotine Patch	0 of 15 (0%)	14 of 15 (93.3%)	0 of 15

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30192444Gandelman 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.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Warren D Taylor, MD, MHSc principal investigator

Vanderbilt University Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Nicotine in people with Major Depressive Disorder, run by Vanderbilt University Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Total MADRS (Montgomery Asberg Depression Rating Scale) Score (time frame: Baseline to week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02816138, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2018.