Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder
2019年5月22日 更新者：Jeff Meyer、Centre for Addiction and Mental Health
The purpose of this study is to determine if translocator protein total distribution volume (TSPO VT) is elevated in major depressive disorder that is not responding to medication and if adding minocycline can affect TSPO VT.
Many remain treatment resistant with common antidepressant treatments and the investigators think it may be due to poor targeting of brain pathologies.
研究概览
详细说明
There will be three Phases in the study. Only MDE subjects will be invited to continue to Phase 2 and 3. Subjects will be invited to continue to the subsequent Phase given they meet entry criteria described below:
Phase 1: The investigators will evaluate whether TSPO is elevated in individuals during a current MDE compared to healthy controls. Eligible participants will receive one [18F]FEPPA PET scan and one MRI scan. Other measures will include urine sample, blood samples for genetic and peripheral biomarker analysis, a neurocognitive battery, mood scales and questionnaires.
Phase 2: Participants who have elevated TSPO VT in Phase 1 and are agreeable to receiving minocycline will be invited to participate in Phase 2. Based on our previous results participants will be considered candidates for Phase 2 if TSPO VT ≥ 10.5 (HAB) or ≥8.5 (MAB) in any of the primary regions of interest (prefrontal cortex, anterior cingulate cortex or insula). Eligible participants will be invited to participate in a randomized, double blind, placebo controlled trial, to receive either minocycline or placebo. After the eight weeks of treatment, participants will receive one [18F]FEPPA PET scan. Other measures will include urine samples, blood samples, mood scales and questionnaires.
Phase 3: If, after the initial eight week treatment period with either minocycline or placebo, any participant continues to have depressive symptoms (17-item Hamilton Depression Rating Scale score ≥ 8) they will be invited to participate in an eight week open label trial of celecoxib. Participants not eligible for Phase 2 may also be invited to participate in Phase 3 directly from Phase 1.
研究类型
介入性
注册 (预期的)
115
阶段
- 第一阶段早期
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Ontario
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Toronto、Ontario、加拿大、M5T 1R8
- Centre for Addiction and Mental Health
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 65年 (成人、年长者)
接受健康志愿者
是的
有资格学习的性别
全部
描述
Group 1 - Current major depressive episode (MDE) secondary to MDD
Inclusion Criteria:
- good physical health with no active medical conditions
- non-cigarette smoking
- no past or current substance abuse or dependence
- negative urine pregnancy test at screening and scan days (for women)
- primary diagnosis of current major depressive episode (MDE) and major depressive disorder (MDD) verified by SCID for DSM IV
- score greater than 19 on the 17 item HDRS
- non-response to a clinical trial of at least one antidepressant given at appropriate clinical dose
- willing to take medication for the duration of the trial and has previously taken antidepressants for the duration of the trial
- presently taking an antidepressant at a standard clinical dose.
Exclusion Criteria:
- history of neurological illness or autoimmune disorders
- never taken a tricyclic antidepressant or an antidepressant that raises norepinephrine
- received treatment with electroconvulsive therapy or mechanical brain stimulation in the previous 6 months
- currently taking medication contraindicated or that may possibly interact with either minocycline or celecoxib
- known intolerance or allergy to minocycline, other tetracyclines, sulfonamides or NSAIDs
- taken diazepam or other benzodiazepine use within the past month, except for lorazepam and clonazepam
- use of anti-inflammatory drugs or tetracyclines lasting ≥1 week within the past month
- history of severe hepatic or renal insufficiency, asthma, allergies, gastrointestinal disease, ischemic heart disease, cerebrovascular disease or congestive heart failure
- lactose intolerance
Group 2 - Healthy Controls - Phase 1 (baseline scan) only
Inclusion criteria:
- score below 8 on the 17 item HDRS
- good physical health
- non-cigarette smoking
- negative urine pregnancy test at screening and scan days (for women)
- negative urine screen for drugs of abuse
Exclusion criteria:
- past or current diagnosis of axis I or axis II disorder as determined by the SCID I and SCID II for DSM IV
- history of psychotropic medication use
- history of neurological illness or autoimmune disorder
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：随机化
- 介入模型：单组作业
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Minocycline
The dose of minocycline would be 50mg per day on week 1, 50mg bid on week 2 and 100mg bid weeks 3-8.
For tapering, the dose will be reduced to 50mg bid for a week, and then stopped.
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50 mg and 100 mg capsule, oral administration
其他名称：
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安慰剂比较：Placebo
The number and appearance of the pills would be identical to those in the minocycline arm.
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Lactose monohydrate in identical gel capsules to minocycline, oral administration.
其他名称：
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其他：Celecoxib
This will be an open label trial for those with Hamilton Depression Rating Scale score ≥ 8 following the minocycline v. placebo trial or those not eligible for Phase 2. Dose of celecoxib will be 100 mg bid for the first week and 200mg bid for weeks 2-8.
For tapering, the dose of celecoxib will be reduced to 100mg bid for one week, and then stopped.
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100 mg and 200 mg capsules, oral administration.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects
大体时间：Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans
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TSPO VT will be measured using [18F]FEPPA positron emission tomography brain scans.
Eligible MDE participants will be randomized to either minocycline or placebo.
Following 8 weeks of either minocycline or placebo treatment, MDE participants will have a second PET scan .
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Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans
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Translocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects
大体时间：Pre-treatment scan will take place up to 8 weeks from initial assessment
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Compare baseline TSPO VT prior to treatment between MDE group and healthy group
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Pre-treatment scan will take place up to 8 weeks from initial assessment
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Change in Hamilton Depression Rating Scale Score
大体时间：Pre- and post-minocycline treatment (8 weeks total between pre- and post-treatment). Pre- and post-celecoxib treatment (8 weeks total between pre- and post-treatment).
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Change in HDRS score following minocycline vs. placebo treatment.
Change in HDRS score following celecoxib treatment.
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Pre- and post-minocycline treatment (8 weeks total between pre- and post-treatment). Pre- and post-celecoxib treatment (8 weeks total between pre- and post-treatment).
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
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Hopkins Verbal Learning Test-Revised
大体时间：Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)
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To assess verbal memory we will administer the Hopkins Verbal Learning Test-Revised to MDE participants before and after treatment.
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Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)
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Brief Visuospatial Memory Test-Revised
大体时间：Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)
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To assess visuospatial memory we will administer the Brief Visuospatial Memory Test-Revised to MDE participants before and after treatment.
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Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)
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Comprehensive Trails Making Test
大体时间：Pre- and post-minocycline or placebo treatment.
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To assess psychomotor speed and attention we will administer the Comprehensive Trails Making Test to MDE participants before and after treatment.
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Pre- and post-minocycline or placebo treatment.
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Genetic sample
大体时间：Phase 1-single sample
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The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA.
The genetic sample will also be used to study sequences of genes that are believed to affect TSPO expression, inflammation, mood and conditions that may predispose to mood disorders.
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Phase 1-single sample
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Blood samples (serum and plasma)
大体时间：Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures).
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Analyses will include complete blood cell count (CBC), ESR, hepatic and renal function.
Peripheral marker analyses will include proteins related to TSPO expression and inflammation.
Plasma minocycline and celecoxib levels will be analyzed.
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Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures).
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Jeffrey H Meyer, MD, PhD、Centre for Addiction and Mental Health; University of Toronto
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2015年2月1日
初级完成 (实际的)
2019年4月1日
研究完成 (实际的)
2019年4月1日
研究注册日期
首次提交
2015年2月4日
首先提交符合 QC 标准的
2015年2月9日
首次发布 (估计)
2015年2月13日
研究记录更新
最后更新发布 (实际的)
2019年5月23日
上次提交的符合 QC 标准的更新
2019年5月22日
最后验证
2019年5月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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