Open Label Extension Study of Depressed Mood Improvement Through Nicotine (Depressed MIND3)
概览
- 阶段
- 2 期
- 干预措施
- Transdermal Nicotine patch
- 疾病 / 适应症
- Depressive Disorder
- 发起方
- Vanderbilt University Medical Center
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Continuous Performance Task (CPT) Performance
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
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 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.
详细描述
The purpose of this open-label extension to the Depressed MIND 3 study will be to gather data on longer-term benefits and safety in patients with late-life depression (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. Investigators 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 an open-label extension of a randomized double blind placebo control trial that will enroll 80 participants over a 3-year period. After randomization and completion of the blinded study phase, participants will be eligible for this 12-week extension. At the completion of Week-12 visit of the Depressed MIND -3, all eligible subjects will be offered enrollment in the open label extension study. Study visits during the treatment period for all subjects will occur approximately 3 weeks with flexible dose titration. This will be followed by a 1-3 week taper phase. The total duration of study participation will be approximately 15 weeks.
研究者
Warren Taylor
Professor of Psychiatry
Vanderbilt University Medical Center
入排标准
入选标准
- •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:
- •Age ≥ 60 years;
- •Diagnosis of major depressive disorder, single or recurrent episode (DSM5);
- •On a stable therapeutic dose of an allowed SSRI or 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
排除标准
- •Other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) or social phobia symptoms occurring in a depressive episode or diagnosis of an attentional disorder, such as Attention Deficit Hyperactivity Disorder (ADHD);
- •Use of other augmentation medication treatments for depression, or ADHD e.g., stimulant medications,, e.g., adjunctive bupropion or other augmenting agents, that the participant does not want to stop, 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;
研究组 & 干预措施
Transdermal Nicotine Patch
Participants will wear nicotine transdermal patches daily for 12-15 weeks. Participants will apply a study patch each morning and remove at bedtime. Active dose will titrate up from 3.5mg to 7mg, and then can optionally be further titrated to a maximum dose of 14mg. After week12, the dose will be slowly tapered over 2-3 weeks.
干预措施: Transdermal Nicotine patch
结局指标
主要结局
Change in Continuous Performance Task (CPT) Performance
时间窗: Baseline to Week 12
Primary cognitive outcome, the CPT is a neuropsychological test that is conducted as part of the NIH EXAMINER Test Battery. Participants are asked to respond to a target image, and not to other images. This test is conducted at baseline and at week12. The specific primary outcome metric is standard error of change in the inter-stimulus hit reaction time or variability between different trials. There is not absolute range, but lower scores indicate decreased variability across trials and overall better performance.
Change in MADRS (Montgomery Asberg Depression Rating Scale) Score
时间窗: Baseline to week 12
Primary mood outcome measured by the total score of the clinician rated MADRS. MADRS will be 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.
次要结局
- NIH EXAMINER Test Battery(Baseline to Week 12)
- Trait Adjectives Task(Baseline to Week 12)
- Ruminative Response Scale(Baseline to Week 12)
- Apathy Evaluation Scale (AES)(Baseline to Week 12)
- Insomnia Severity Index(Baseline to Week 12)
- Selective Reminding Task(Baseline to Week 12)
- Penn State Worry Questionnaire (PSWQ(Baseline to Week 12)
- Attentional Control Scale(Baseline to Week 12)
- Fatigue Severity Scale(Baseline to Week 12)
- Monetary Incentive Delay Task(Baseline to Week12)
- General Anxiety Disorder Scale (7 Item)(Baseline to Week 12)
- PROMIS Applied Cognition Abilities Short(Baseline to Week 12)
- Probabilistic Selection Task(Baseline and at week 12)