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.
随着芬太尼(高效合成阿片类药物)的泛滥,美国严峻的阿片类药物危机仍在继续
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
Differential brain response to successful and failed response inhibition: Cocaine-dependent vs. healthy subjects
- DOI:
10.1016/j.drugalcdep.2015.07.582 - 发表时间:
2015-11-01 - 期刊:
- 影响因子:
- 作者:
Jesse Suh;K. Jagannathan;Ronald Ehrman;Marina Goldman;Zachary A. Monge;Elliott Berkowitz-Sturgis;Teresa Franklin;Kathleen Marquez;Regina Szucs-Reed;Charles 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
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: