A 6 Month, Phase II Randomized, Double-Blind, Placebo Controlled, Flexible Dosing, Crossover Trial of Atomoxetine in Subjects With Mild Cognitive Impairment.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Change in Interleukin 1 (IL 1-alpha) in Cerebrospinal Fluid (CSF) in Subjects With Mild Cognitive Impairment (MCI) Treated With Atomoxetine/Inactive Compound Compared to Subjects Treated With Inactive Compound / Atomoxetine
研究概览
简要总结
The purpose of this study is to evaluate the safety of atomoxetine and its effect primarily on the biologic markers (substances that may indicate the presence of a disease) in the cerebrospinal fluid (CSF) of participants diagnosed with Mild Cognitive Impairment (MCI). Additionally, information will be gathered to identify the dose of atomoxetine that is most beneficial, and how taking this medication affects thinking and behavior, as well as imaging and blood biomarkers.The study will also explore rates of change in biomarkers of neurodegeneration (Aß, tau, brain atrophy rates). The results of this research will help determine if atomoxetine alters signs of inflammation and other biomarkers associated with Alzheimer's disease.
详细描述
The Alzheimer's Disease (AD) epidemic is a looming crisis, with an urgent need for new therapies to delay or prevent symptom onset and progression. Advances in AD biomarker research have demonstrated changes in amyloid, brain metabolism, and other pathophysiologies prior to the onset of memory loss, with some markers possibly changing one or two decades earlier. Since MCI coincides with the onset of brain atrophy, this early stage of AD pathogenesis may offer a critical window of time to initiate novel therapies aimed at the secondary wave of events that lead to progressive neurodegeneration.
From recently emerged basic research in animal models of AD: loss of norepinephrine (NE) incites a pro-inflammatory condition that is neurotoxic and reduces Aß clearance, and remarkably, rescue of norepinephrine reverses these effects and slows neurodegeneration. This study seeks to extend this proof-of-concept to humans for the first time. The study proposes that atomoxetine, a selective norepinephrine transport inhibitor, is an ideal drug to translate these findings to humans because it is already FDA-approved and safe in the elderly
Subjects with mild cognitive impairment (amnestic or multi-domain subtypes) will be randomly assigned to treatment with placebo or flexible doses of the Norepinephrine Transporter (NET) inhibitor atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose. Participants will be treated for upto 29 weeks, and will undergo venous blood draws and lumbar puncture for biomarker analyses at baseline and up to weeks 29. At a maximum of 29 weeks time point, subjects assigned to active treatment will crossover to placebo and those subjects who were initially randomized to placebo will initiate active treatment.
Participants who complete study are eligible to receive open-label Atomoxetine at the maximum-tolerated dose received during the double-blind phase of the trial. Subjects in the open label are seen every at week 29 upto maximum of 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Atomoxetine / Inactive Compound
Participants in this arm received atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose for up to weeks 29 and are then crossed over to Inactive compound group
干预措施: Atomoxetine (Drug)
Atomoxetine / Inactive Compound
Participants in this arm received atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose for up to weeks 29 and are then crossed over to Inactive compound group
干预措施: Placebo (Drug)
Inactive compound / Atomoxetine
Subjects in this arm received a matching placebo that have inactive compound for up to weeks 29 and then are crossed over to receive active treatment of Atomoxetine
干预措施: Atomoxetine (Drug)
Inactive compound / Atomoxetine
Subjects in this arm received a matching placebo that have inactive compound for up to weeks 29 and then are crossed over to receive active treatment of Atomoxetine
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Interleukin 1 (IL 1-alpha) in Cerebrospinal Fluid (CSF) in Subjects With Mild Cognitive Impairment (MCI) Treated With Atomoxetine/Inactive Compound Compared to Subjects Treated With Inactive Compound / Atomoxetine
时间窗: Baseline, Week 29 and Week 58
This study will examine the effects of Atomoxetine and Inactive compound on biomarkers of inflammation by measuring and comparing the levels of Interleukin 1 (IL 1-alpha) using the assay of CSF at Baseline, Week 29 and Week 58 among the two groups. The study hypothesizes that the period that participants are treated with atomoxetine will have reductions in levels of these pro-inflammatory biomarkers among the two groups.
Change in Mean Level of Thymus-Expressed Chemokine (TECK) in Cerebrospinal Fluid (CSF) in Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine
时间窗: Baseline, Week 29 and Week 58
This study will examine the effect of Atomoxetine and Inactive Compound on biomarkers of inflammation by measuring and comparing the mean levels of Thymus-Expressed Chemokine (TECK). These levels are measured using the assay of CSF at Baseline, Week 29 and Week 58. The study hypothesizes that the period that participants are treated with atomoxetine will have reduction in levels of these markers among both groups.
Number of All Adverse Events Among the Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine Compared to the Participants Treated With Placebo/Inactive Compound
时间窗: Up to Week 58
Safety was assessed by number of all adverse events among the participants treated with Atomoxetine compared to the participants treated with Placebo throughout the study. The Adverse Event assessment was done at each study visit through their participation in the study.
Number of Participants That Drop Out of the Study Among the Participants Treated With Atomoxetine When Compared to the Participants Treated With Inactive Compound (Placebo)
时间窗: Up to Week 58
Tolerability is measured by comparing the drop out rate among the participants treated with Atomoxetine to the participants treated with inactive compound (Placebo). Study predicts that treatment-associated (Atomoxetine Group) drop out rate will be \< 15% .
次要结局
- Rate of Cerebral Blood Flow in Subjects With Mild Cognitive Impairment MCI Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine(Baseline, Week 29, Week 58)
- Change in FluoroDeoxyGlucose (FDG) Uptake in Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine(Baseline, Week 29 and Week 58)
研究者
Allan I Levey, MD
Professor and Chair, Department of Neurology
Emory University