Neuroimmune Treatment for AUD: Testing Moderators of Clinical Response and Mechanisms of Action
AUD 的神经免疫治疗:测试临床反应的调节因素和作用机制
基本信息
- 批准号:10664833
- 负责人:
- 金额:$ 4.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAffectiveAlcohol consumptionAlcoholsAnhedoniaAnimal ModelAnti-Inflammatory AgentsAnxietyArousalBehaviorBiological AssayBiological MarkersBlood specimenBrainC-reactive proteinCaringCentral Nervous SystemChronicChronic DiseaseClinicalClinical DataClinical TrialsComplexDataDevelopmentDisciplineDouble-Blind MethodEnrollmentFemaleFosteringFundingHeavy DrinkingHumanImmuneImmune responseImmunologic MarkersImmunotherapyImpaired cognitionIndividualInflammationInflammatoryInterventionKnowledgeLaboratoriesLaboratory FindingLinkLiteratureMediatingMediationMedicineMental DepressionMental disordersMentorsMethodsModelingMotivationNational Research Service AwardsNeuroimmuneOutcomePeripheralPharmaceutical PreparationsPharmacotherapyPhysiologicalPre-Clinical ModelPropertyPsychoneuroimmunologyPublic HealthRandomized, Controlled TrialsReceptor CellRecoveryRelapseResearchResearch PersonnelResearch PriorityRewardsSafetySamplingScientistSex DifferencesStressSystemTechniquesTestingTrainingTreatment EfficacyTreatment outcomeUnited States National Institutes of Healthaddictionalcohol abuse therapyalcohol cravingalcohol related problemalcohol use disorderantagonistcareerchronic alcohol ingestioncommon symptomcravingcytokinedemographicsdepressive symptomsdrinkingevidence baseimmune activationimmune functionimmunoregulationimprovedindexinginflammatory markerinfliximabinhibitorinterestlensmeetingsmultilevel analysisnegative affectneuroinflammationnovelpersonalized medicinephosphoric diester hydrolaseprecision medicinepredicting responserandomized, clinical trialsrecruitresponsescreeningsexskillssubstance usesuccesssymptomatologytheoriestreatment response
项目摘要
PROJECT SUMMARY/ ABSTRACT
Only a small proportion of individuals with past-year AUD received treatment. As such, development of
novel, efficacious pharmacotherapies for AUD is a high research priority that may lead to higher treatment
utilization and success rates. Establishing moderators of treatment response and mechanisms of action is an
imperative step towards identifying predictors of good clinical response and furthering precision medicine.
Modulation of immune function is one promising treatment target for addiction. Through activation of immune
cell receptors, sustained heavy alcohol use induces a proinflammatory state, which contributes of AUD
symptomatology. Negative affect is multi-faceted construct and common feature of AUD that is consistently
associated with poorer treatment outcomes and may be linked to inflammation induced by chronic alcohol use.
Anti-inflammatory therapies are shown to reduce levels of negative affect among individuals with psychiatric
disorders. As such, reductions in facets of negative affect may be a potential mechanism of action involved in
neuroimmune modulation in AUD. In regard to candidate moderators, research across disciplines shows that a
particularly pronounced inflammatory profile might be more amenable to neuroimmune treatment. Examination
of sex differences in response to immune treatment is also supported by several fields of research and
delineated by NIH as a priority consideration that can inform clinical interventions. This proposal is based on
recent indications that ibudilast, a neuroimmune modulator, is a potentially efficacious pharmacotherapy for
AUD. An initial screening of ibudilast in the Sponsor's laboratory showed that following stress exposure,
ibudilast promoted a stronger recovery of positive affect and strengthened the influence of negative affect on
craving. The objective of this NRSA application is to foster my development as a clinical scientist with a focus
on medications development for AUD, psychoneuroimmunology, and quantitative methods. This proposal will
draw from an ongoing and funded 12-week clinical trial of ibudilast recruiting a treatment-seeking sample of
AUD. Given the limited knowledge about how this class of therapy operates in human samples of AUD and
who is most treatment responsive, the proposed study will investigate potential moderators of clinical response
and mechanisms of action by leveraging data from this clinical trial of ibudilast. Specifically, Aim #1 tests the
hypothesis that facets of negative affect will significantly mediate the relationship between treatment and heavy
drinking. Aim #2 tests the hypothesis that peripheral proinflammatory biomarkers and sex will serve as
moderators of clinical response to ibudilast. These Aims will be tested using a sophisticated analytic approach
including longitudinal multilevel moderation and mediation models. The present study represents an important
step in further immune pharmacotherapies for AUD and, with the support of my mentoring team, my scientific
development as an independent clinical alcohol researcher with an interest in medications development.
项目总结/摘要
只有一小部分患有去年AUD的人接受了治疗。因此,发展
针对AUD的新型有效药物疗法是一项高度优先的研究,可能导致更高的治疗水平
使用率和成功率。建立治疗反应和作用机制的调节剂是一种有效的方法。
确定良好临床反应的预测因素和进一步推进精准医疗的必要步骤。
调节免疫功能是成瘾的一个有前途的治疗靶点。通过激活免疫
细胞受体,持续大量饮酒诱导促炎状态,这有助于AUD
医学。负面情绪是多方面的结构,也是澳元的共同特征,
与较差的治疗结果相关,并可能与慢性酒精使用引起的炎症有关。
抗炎疗法被证明可以降低精神病患者的负面影响水平。
紊乱因此,消极影响方面的减少可能是一种潜在的作用机制,
AUD的神经免疫调节关于候选主持人,跨学科的研究表明,
特别明显的炎症特征可能更适合神经免疫治疗。考试
免疫治疗反应的性别差异也得到了几个研究领域的支持,
NIH将其列为可以为临床干预提供信息的优先考虑因素。该提案基于
最近的迹象表明,异丁司特,一种神经免疫调节剂,是一种潜在有效的药物治疗,
澳元。在申办者实验室中对异丁司特的初步筛选显示,在应激暴露后,
异丁司特促进了积极情感的恢复,并加强了消极情感的影响。
渴望这个NRSA应用程序的目的是促进我作为一个临床科学家的发展,重点是
关于AUD的药物开发,心理神经免疫学和定量方法。这项建议会
从一项正在进行的、受资助的为期12周的异丁司特临床试验中抽取了一个寻求治疗的样本,
澳元。鉴于对这类疗法如何在AUD的人类样本中起作用的知识有限,
谁是最治疗反应,拟议的研究将调查潜在的调节临床反应
和作用机制,利用异丁司特临床试验的数据。具体来说,目标1测试了
假设负面影响的方面将显着介导治疗和重度之间的关系,
喝酒目的#2检验外周促炎生物标志物和性别将作为
异丁司特临床反应的调节剂。这些目标将使用复杂的分析方法进行测试
包括纵向多层次缓和和调解模式。本研究是一项重要的
在我的指导团队的支持下,我的科学家们正在进一步研究AUD的免疫药物疗法。
作为一个独立的临床酒精研究者,对药物开发感兴趣。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Lindsay Meredith Broussard其他文献
Lindsay Meredith Broussard的其他文献
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{{ truncateString('Lindsay Meredith Broussard', 18)}}的其他基金
Neuroimmune Treatment for AUD: Testing Moderators of Clinical Response and Mechanisms of Action
AUD 的神经免疫治疗:测试临床反应的调节因素和作用机制
- 批准号:
10388776 - 财政年份:2022
- 资助金额:
$ 4.23万 - 项目类别:
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