A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
基本信息
- 批准号:9895139
- 负责人:
- 金额:$ 52.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AdherenceAdjuvant AnalgesicAffectiveAffinityAgeAgonistAlcoholsAmericanAmygdaloid structureAttentionAutomobile DrivingBaltimoreBehavioralBrainBrain imagingBuprenorphineCannabidiolCannabisCause of DeathClinicalClinical TreatmentClinical TrialsCocaineCountryCuesDataDevelopmentDopamineEvaluationFentanylGenetic PolymorphismGlobus PallidusGoalsHumanImageInjectableInjectionsInpatientsKnowledgeLaboratoriesLifeMeasuresMedialMethadoneMotivationNaltrexoneNeurosciencesNicotineOpioidOpioid ReceptorOpioid agonistOutcome MeasureOutpatientsPatientsPennsylvaniaPharmaceutical PreparationsPhiladelphiaPlacebosPositron-Emission TomographyRandomizedRelapseResearchResearch PersonnelResourcesRewardsRisk-TakingSavingsSignal TransductionSpeedSubgroupSubstance Use DisorderTestingTracerUniversitiesUrineVentral StriatumVentral Tegmental AreaWithdrawal SymptomWorkaddictionbasebehavioral responseclinical efficacycocaine usedrug cravingexperiencegamma-Aminobutyric Acidhypocretinillicit drug useimaging probeimprovedinnovationmedication compliancemedication-assisted treatmentmortalityneuroimagingnon-opioid analgesicnovelopioid epidemicopioid mortalityopioid overdoseopioid useopioid use disorderopioid withdrawaloverdose deathpre-clinicalprescription opioidpreventprimary endpointreceptorrecruitresponsesecondary endpointsynthetic opioidtooltreatment site
项目摘要
The nation’s grim opioid crisis surges on, with the fentanyls (high potency synthetic opioids) driving
unprecedented mortality rates. Drug overdose deaths are now the leading cause of death in those under age
50, with more than 47,000 Americans dying of opioid overdose in 2017. As of December 2018, Philadelphia
had the third highest rate of opioid overdose deaths in the country (out-ranked only by Pittsburgh and Baltimore).
Fentanyl is present in 84% of the fatal opioid overdoses in Philadelphia. Medication-assisted treatment (MAT)
for opioid use disorders – whether full opioid agonist (methadone), partial opioid agonist (buprenorphine), or a
full antagonist (naltrexone) – is critical for reducing opioid use, and for preventing overdose deaths.
Unfortunately, compliance with these life-saving medications is often poor, with ancillary use of non-opioid drugs
(especially cocaine) as a common culprit. Cocaine is found in almost half of the opioid overdose deaths in
Philadelphia.
Identifying promising adjunctive medications that reduce cocaine and other illicit drug use during MAT
could improve adherence and save thousands of lives each year. Further, measuring how these medications
“engage” the intended brain targets will speed rational medication development. Toward both these goals, we
will cohere significant local addiction resources and research strengths (e.g., in clinical trials and human
neuroimaging) to establish a Clinical Laboratory with Integrated Neuroscience (CLIN) for Evaluation of
Medications for Substance Use Disorders at the University of Pennsylvania Center for Studies of Addiction. The
initial 2-year demonstration project in the UG1 will test the promise of cariprazine, a candidate anti-relapse
medication with high D3-affinity, both for preliminary clinical efficacy (reduced illicit drug use, and improved
adherence to life-saving naltrexone), and for target engagement (e.g., blunting of drug cue-triggered limbic
activation) in patients with opioid use disorders. The project will recruit detoxified opioid patients (up to n=75)
within a proximal network of 10 clinical treatment sites. Eligible patients will be randomly-assigned (2:1 ratio) to
cariprazine (Vraylar, 1.5 mg daily) vs. placebo, and all will receive up to 3 monthly injections of extended release
injectable naltrexone (Vivitrol, 380 mg) in a 12 week outpatient trial (Early Efficacy). A subgroup of imaging-
eligible patients will also receive inpatient Target Engagement measures (brain imaging probes for reward and
inhibition) prior to beginning the outpatient trial. We will also examine (Exploratory Aim) the impact of
hypothesis- driven genetic polymorphisms (e.g., rs6280 for DA D3 receptor) on both the brain and clinical
response to the D3 medication. Summary: The highly experienced CLIN team, innovative brain tools, and the
novel testing of a D3 medication to improve adherence to naltrexone, are clear strengths of the initial
demonstration project, and increase the likelihood that it will both provide new knowledge and save lives. Out-
years CLIN strengths include the promise of new candidate medications (e.g., GABA B PAMs, orexin
antagonists, cannabidiol) and new, highly-selective PET tracers for measuring opioid receptors and medication
occupancy.
国家严峻的阿片类药物危机激增,芬太尼(高效合成阿片类药物)
空前的死亡率。药物过量死亡现在是那些未成年人死亡的主要原因
50,2017年有超过47,000名美国人死于阿片类药物过量。截至2018年12月,费城
阿片类药物过量死亡率在全国排名第三(仅次于匹兹堡和巴尔的摩)。
费城84%的致命阿片类药物过量病例中含有芬太尼。药物辅助治疗(MAT)
对于阿片类药物使用障碍-无论是完全阿片类药物激动剂(美沙酮),部分阿片类药物激动剂(丁丙诺啡),或
完全拮抗剂(纳洛酮)-对于减少阿片类药物的使用和预防过量死亡至关重要。
不幸的是,这些救命药物的依从性往往很差,辅助使用非阿片类药物
(特别是可卡因)作为一个共同的罪魁祸首。可卡因被发现在近一半的阿片类药物过量死亡,
费城
确定减少MAT期间可卡因和其他非法药物使用的有希望的替代药物
可以提高依从性,每年挽救数千人的生命。此外,测量这些药物
“参与”预期的大脑目标将加速合理的药物开发。为了实现这两个目标,我们
将凝聚重要的当地成瘾资源和研究力量(例如,在临床试验和人类
神经影像学),以建立一个临床实验室与综合神经科学(CLIN)的评价
宾夕法尼亚大学成瘾研究中心的物质使用障碍药物。的
UG 1的初始2年示范项目将测试卡利拉嗪(一种候选抗复发药物)的前景
具有高D3亲和性的药物,既用于初步临床疗效(减少非法药物使用,
坚持使用救命的纳洛酮),以及用于目标接合(例如,药物线索触发的边缘系统钝化
激活)在阿片类药物使用障碍的患者中。该项目将招募阿片类药物脱毒患者(最多n=75)
在10个临床治疗点的近端网络内。合格患者将随机分配(2:1比例)至
卡利拉嗪(Vraylar,1.5 mg/天)与安慰剂,所有患者将接受长达3个月的缓释注射
注射纳洛酮(Vivitrol,380 mg)在12周的门诊试验(早期疗效)。影像学的一个亚组-
符合条件的患者还将接受住院目标参与措施(脑成像探头奖励,
在开始门诊试验之前进行抑制。我们还将研究(探索性目标)的影响,
假设驱动的遗传多态性(例如,rs6280用于DA D3受体)对脑和临床
对D3药物的反应。总结:经验丰富的CLIN团队,创新的大脑工具,
D3药物的新测试,以提高对纳洛酮的依从性,是最初研究的明显优势。
这将是一个示范项目,并增加提供新知识和拯救生命的可能性。出去-
多年来CLIN的优势包括新候选药物的前景(例如,GABA B PAM,食欲素
拮抗剂,大麻二酚)和新的高选择性PET示踪剂,用于测量阿片受体和药物
占用率
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Anna Rose Childress其他文献
Can we use cue-related brain responses to predict which cocaine patients will take more risks?
- DOI:
10.1016/j.drugalcdep.2014.09.489 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Zachary A. Monge;K. Jagannathan;Jesse Suh;Ronald Ehrman;Kimberly A. Young;Teresa Franklin;Daniel Langleben;Charles P. O’Brien;Anna Rose Childress - 通讯作者:
Anna Rose Childress
Frontal vs. limbic predictors of inhibitory success in addiction
- DOI:
10.1016/j.drugalcdep.2014.02.112 - 发表时间:
2014-07-01 - 期刊:
- 影响因子:
- 作者:
Anna Rose Childress;Y. Li;M. Goldman;J.J. Suh;R. Ehrman;S. Lam;Z. Singer;Teresa R. Franklin;D. Langleben;K. Young;Reagan R. Wetherill;Michael J. Gawrysiak;C.P. O’Brien - 通讯作者:
C.P. O’Brien
Baclofen, a GABA B Agonist, reduces risk-taking and reveals the relationship between brain responses to drug cues and risk-taking in cocaine-addicted patients
- DOI:
10.1016/j.drugalcdep.2014.02.684 - 发表时间:
2014-07-01 - 期刊:
- 影响因子:
- 作者:
Kimberly A. Young;Y. Li;D.C.S. Roberts;C. Lejuez;Teresa R. Franklin;Jesse Suh;M. Goldman;Kyle M. Kampman;Reagan R. Wetherill;C.P. O’Brien;Anna Rose Childress - 通讯作者:
Anna Rose Childress
Lower oxidative stress in umbilical blood cord of newborns exposed to crack during pregnancy
- DOI:
10.1016/j.drugalcdep.2014.09.676 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Claudia M. Szobot;Maria Zavaschi;V. Mardini;F. Kapczinski;Márcia Kauer-Sant’anna;Gabriela Colpo;Bianca Aguiar;Gabrielle Cunha;L. Manna;Anna Rose Childress;Daniel Langleben;K.M. Cereser;L.A. Rohde - 通讯作者:
L.A. Rohde
A higher hill to climb! Older cocaine-addicted patients viewing 500 ms cocaine cues have reduced activation of modulatory circuits and increased activation of motivational circuits
- DOI:
10.1016/j.drugalcdep.2015.07.423 - 发表时间:
2015-11-01 - 期刊:
- 影响因子:
- 作者:
Zachary A. Monge;K. Jagannathan;Jesse Suh;Ronald Ehrman;Ze Wang;Teresa Franklin;Reagan R. Wetherill;Kimberly A. Young;Michael J. Gawrysiak;Daniel Langleben;Charles P. O’Brien;Anna Rose Childress - 通讯作者:
Anna Rose Childress
Anna Rose Childress的其他文献
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{{ truncateString('Anna Rose Childress', 18)}}的其他基金
A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
- 批准号:
10395761 - 财政年份:2021
- 资助金额:
$ 52.99万 - 项目类别:
A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
- 批准号:
10348202 - 财政年份:2020
- 资助金额:
$ 52.99万 - 项目类别:
A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders
综合神经科学 (CLIN) 临床实验室,用于药物滥用障碍药物的早期评估
- 批准号:
10576815 - 财政年份:2020
- 资助金额:
$ 52.99万 - 项目类别:
Targeting dopamine D3 receptors in cocaine addiction
靶向可卡因成瘾中的多巴胺 D3 受体
- 批准号:
9249538 - 财政年份:2016
- 资助金额:
$ 52.99万 - 项目类别:
Targeting dopamine D3 receptors in cocaine addiction
靶向可卡因成瘾中的多巴胺 D3 受体
- 批准号:
9926357 - 财政年份:2016
- 资助金额:
$ 52.99万 - 项目类别:
T32 Translational Addiction Research Fellowship Program
T32 转化成瘾研究奖学金计划
- 批准号:
9393067 - 财政年份:2016
- 资助金额:
$ 52.99万 - 项目类别:
Weight History, Brain Activation to Food Cues and Eating Disorder Psychopathology
体重史、食物线索的大脑激活和饮食失调精神病理学
- 批准号:
8678241 - 财政年份:2014
- 资助金额:
$ 52.99万 - 项目类别:
Weight History, Brain Activation to Food Cues and Eating Disorder Psychopathology
体重史、食物线索的大脑激活和饮食失调精神病理学
- 批准号:
9076365 - 财政年份:2014
- 资助金额:
$ 52.99万 - 项目类别:
Do brain differences influence HIV risk behavior? A study of young urban women
大脑差异会影响艾滋病毒危险行为吗?
- 批准号:
8513416 - 财政年份:2012
- 资助金额:
$ 52.99万 - 项目类别:
Do brain differences influence HIV risk behavior? A study of young urban women
大脑差异会影响艾滋病毒危险行为吗?
- 批准号:
8330061 - 财政年份:2012
- 资助金额:
$ 52.99万 - 项目类别: