Ignite Creation Date:
2024-05-06 @ 6:40 PM
Last Modification Date:
2024-10-26 @ 2:52 PM
Study NCT ID:
NCT05746273
Status:
RECRUITING
Last Update Posted:
2024-05-22
First Post:
2023-02-14
Brief Title:
Depressed Mood Improvement Through Nicotine Dosing 3
Sponsor:
Vanderbilt University Medical Center
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
Nicotinic Modulation of the Cognitive Control System in Late-Life Depression R33 Phase
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DepMIND3
Brief 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 blinded study will expand past open-label trials supporting potential benefit in LLD It will examine TDNs effect on depression severity and cognitive control functions measured by neuropsychological testing The study will evaluate 60 eligible and enrolled participants over a 3-year period
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 blinded study will expand past open-label trials supporting potential benefit in LLD It will examine TDNs effect on depression severity and cognitive control functions measured by neuropsychological testing The study will evaluate 60 eligible and enrolled participants over a 3-year period
Detailed Description:
The purpose of the Depressed MIND3 study is to determine whether blinded placebo-controlled administration of transdermal nicotine results in significant cognitive clinical and functional improvement in participants with 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
We 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 a randomized double blind placebo control trial that will enroll 80 participants over a 3-year period Participants will be randomized 21 to receive either active transdermal nicotine TDN patches or matching placebo patches Participants will apply patches daily for 12 weeks followed by a 3-week taper period
The Aims of this blinded trial are to 1 validate target engagement and determine whether change in brain activation to an emotional Stroop task is related to improvement in depression severity and cognitive performance and 2 determine the specificity of TDNs effects by examining whether changes in the default mode network DMN or other regions occur with TDN and if so are they related to change in clinical measures
AIM 1 Examine how TDNs neural circuit changes affect depressive symptoms in a blinded RCT
Hyp 1A Compared with placebo TDN administration will significantly reduce the Stroop BOLD response on functional Magnetic Resonance Imaging This change will be associated with reduction in depression severity by the Montgomery-Asberg Depression Rating Scale MADRS
Hyp 1B Change in the Stroop BOLD response of other brain regions with TDN administration specifically the DMN will not be significantly associated with change in depression severity
Hyp 1C Compared with placebo TDN will improve depression severity measured by MADRS primary clinical outcome reduce apathy and rumination measured by self-report and reduce negative self-referential thinking measured by the Trait Adjectives Task secondary outcomes
AIM 2 Examine how TDNs circuit changes affect CCN-mediated cognitive performance
Hyp 2A Reduction in the Stroop BOLD response will be associated with improvement in attention working memory and episodic memory performance Change in the Stroop BOLD response of other regions specifically the DMN will not be associated with change in task performance
Hyp 2B Compared with placebo nicotine will improve performance on tasks of attention working memory and episodic memory secondary outcomes
We 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 a randomized double blind placebo control trial that will enroll 80 participants over a 3-year period Participants will be randomized 21 to receive either active transdermal nicotine TDN patches or matching placebo patches Participants will apply patches daily for 12 weeks followed by a 3-week taper period
The Aims of this blinded trial are to 1 validate target engagement and determine whether change in brain activation to an emotional Stroop task is related to improvement in depression severity and cognitive performance and 2 determine the specificity of TDNs effects by examining whether changes in the default mode network DMN or other regions occur with TDN and if so are they related to change in clinical measures
AIM 1 Examine how TDNs neural circuit changes affect depressive symptoms in a blinded RCT
Hyp 1A Compared with placebo TDN administration will significantly reduce the Stroop BOLD response on functional Magnetic Resonance Imaging This change will be associated with reduction in depression severity by the Montgomery-Asberg Depression Rating Scale MADRS
Hyp 1B Change in the Stroop BOLD response of other brain regions with TDN administration specifically the DMN will not be significantly associated with change in depression severity
Hyp 1C Compared with placebo TDN will improve depression severity measured by MADRS primary clinical outcome reduce apathy and rumination measured by self-report and reduce negative self-referential thinking measured by the Trait Adjectives Task secondary outcomes
AIM 2 Examine how TDNs circuit changes affect CCN-mediated cognitive performance
Hyp 2A Reduction in the Stroop BOLD response will be associated with improvement in attention working memory and episodic memory performance Change in the Stroop BOLD response of other regions specifically the DMN will not be associated with change in task performance
Hyp 2B Compared with placebo nicotine will improve performance on tasks of attention working memory and episodic memory secondary outcomes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 4R33MH122464-03 | NIH | None | httpsreporternihgovquickSearch4R33MH122464-03 |