Depressed Mood Improvement Through Nicotine Dosing (Depressed MIND Study)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in Total MADRS (Montgomery Asberg Depression Rating Scale) Score
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Transdermal nicotine patch
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.
干预措施: Nicotine (Drug)
结局指标
主要结局
Change in Total 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 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
时间窗: 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.
次要结局
- Change in Penn State Worry Questionnaire (PSWQ)(Baseline to week 12)
- Change in Ruminative Response Scale Total Score(Baseline to week 12)
- Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score(Baseline to week 12)
- Change in Apathy Evaluation Scale (AES)(Baseline to 12 weeks)
- Change in NYU (New York University) Paragraph Recall Performance(Baseline to week 12)
- Change in Choice Reaction Time (CRT) Performance(Baseline to week 12)
- Change in One-back Test Performance(Baseline to week 12)
- Change in MFQ (Memory Frequency Questionnaire) Score(Baseline to week 12)
研究者
Warren Taylor
Associate Professor of Psychiatry
Vanderbilt University Medical Center