2/2-Pramipexole in Bipolar Disorder: Targeting Cognition

2/2-普拉克索治疗双相情感障碍:针对认知

基本信息

项目摘要

DESCRIPTION (provided by applicant): Despite advances in the treatment of bipolar disorder, most patients do not achieve complete inter-episode recovery and functional disability is common. During periods of relative remission, many patients continue to experience neurocognitive dysfunction. These persistent features of the illness represent critical treatment targets, as they do not adequately improve with standard mood stabilizing medications and they are strongly associated with functional disability and poor quality of life. In prior work by our group (Burdick et al. 2012), we reported preliminary evidence of a significant efficacy signal in a subset of bipolar patients who participated in a controlled cognitive enhancement trial of the D2/D3 agonist, pramipexole (Mirapex(c)). In conducting this previous study, we noted several important methodological limitations and illness-related confounds that require follow-up using a modified approach in order to adequately test the safety and efficacy of this agent in treating cognitive dysfunction in bipolar disorder. Thus, we propose a 2-site, collaborative, 24-week, randomized, placebo-controlled, adjunctive study to evaluate the safety and efficacy of pramipexole on neurocognitive functioning in 100 affectively-stable bipolar patients. We have modified the design from the prior trial to optimize the likelihood of detecting a positive signalby addressing several of the identified previous limitations by: 1) increasing the maximum daily dose~ 2) including patients who are affectively-stable with objective evidence of cognitive impairment~ 3) stratifying randomization based upon concomitant antipsychotic treatment~ and 4) increasing the duration of the trial to 6 months in an effort to address longer term safety and efficacy as well as potential improvement in everyday functioning. Pramipexole is approved by the US FDA for Parkinson's disease and Restless Leg Syndrome. In an off-label application, we will administer flexibly-dosed pramipexole (1-3 mg/day) vs. placebo to 100 stable patients with bipolar I disorder for 24 weeks. We will measure patients' performance on tasks of attention, memory and higher order cognition, using several paper-pencil and computerized tests, before pramipexole is administered, at week 4, week 8, week 16, and again at the end of the 24-week study. In addition, we will include several novel affective-neuroscience-based measures to gain insight into pramipexole's effect on the neural networks associated with DA-based reward processing. Finally, we will also investigate the effects of pramipexole on measures of functional capacity and community functions. We will closely monitor patients for unforeseen changes in mood symptoms that are deemed to place them at risk for developing mania or depression and will discontinue the trial as deemed necessary. We expect that findings from this study will provide a definitive go/no-go decision regarding the pursuit of this agent as a cognitive enhancer in bipolar disorder. Regardless of primary outcome, we expect that this trial will provide additional important data related to D2/D3-based reward processing in affective disorders.
描述(由申请人提供):尽管双相情感障碍的治疗取得了进展,但大多数患者并未实现完全的发作间恢复,并且功能障碍很常见。在相对缓解期间,许多患者继续经历神经认知功能障碍。这些疾病的持续特征代表了关键的治疗目标,因为标准情绪稳定药物无法充分改善它们,并且与功能障碍和生活质量差密切相关。在我们小组之前的工作中(Burdick et al. 2012),我们报告了初步证据,表明在 参加 D2/D3 激动剂普拉克索 (Mirapex(c)) 对照认知增强试验的双相情感障碍患者子集。在进行之前的研究时,我们注意到一些重要的方法学局限性和与疾病相关的混淆,需要使用改进的方法进行随访,以便充分测试该药物治疗双相情感障碍认知功能障碍的安全性和有效性。因此,我们提出了一项 2 中心、协作、24 周、随机、安慰剂对照、辅助研究,以评估普拉克索对 100 名情感稳定的双相情感障碍患者神经认知功能的安全性和有效性。我们修改了先前试验的设计,通过解决先前确定的几个限制,优化检测到阳性信号的可能性:1)增加每日最大剂量〜2)包括情绪稳定且有认知障碍客观证据的患者~ 3) 基于伴随抗精神病药物的分层随机化 ~ 和 4) 将试验持续时间延长至 6 个月,以解决长期安全性和 功效以及日常功能的潜在改善。 普拉克索已获得美国 FDA 批准用于治疗帕金森病和不宁腿综合症。 在一项超说明书应用中,我们将向 100 名稳定的 I 型双相情感障碍患者施用灵活剂量的普拉克索(1-3 毫克/天)与安慰剂,为期 24 周。我们将在给予普拉克索之前、第 4 周、第 8 周、第 16 周以及在 24 周结束时再次使用多种纸笔和计算机测试来测量患者在注意力、记忆力和高阶认知任务方面的表现。周学习。此外,我们将包括几种新颖的基于情感神经科学的测量方法,以深入了解普拉克索对与基于 DA 的奖励处理相关的神经网络的影响。最后,我们还将研究普拉克索对功能能力和社区功能测量的影响。 我们将密切监测患者情绪症状的不可预见的变化,这些变化被认为会使他们面临躁狂或抑郁的风险,并将在必要时停止试验。我们期望这项研究的结果将为该药物作为双相情感障碍的认知增强剂的追求提供明确的决定。无论主要结果如何,我们预计该试验将提供与情感障碍中基于 D2/D3 的奖励处理相关的额外重要数据。

项目成果

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Anil K Malhotra其他文献

Anil K Malhotra的其他文献

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{{ truncateString('Anil K Malhotra', 18)}}的其他基金

Striatal Connectivity and Clinical Outcome in Psychosis
纹状体连接性和精神病的临床结果
  • 批准号:
    10369158
  • 财政年份:
    2021
  • 资助金额:
    $ 29.49万
  • 项目类别:
Connectivity Biomarkers of Clinical Response in Treatment Resistant Schizophrenia
难治性精神分裂症临床反应的连通性生物标志物
  • 批准号:
    9239186
  • 财政年份:
    2017
  • 资助金额:
    $ 29.49万
  • 项目类别:
Connectivity Biomarkers of Clinical Response in Treatment Resistant Schizophrenia
难治性精神分裂症临床反应的连通性生物标志物
  • 批准号:
    9891084
  • 财政年份:
    2017
  • 资助金额:
    $ 29.49万
  • 项目类别:
Connectivity Biomarkers of Clinical Response in Treatment Resistant Schizophrenia
难治性精神分裂症临床反应的连通性生物标志物
  • 批准号:
    10084173
  • 财政年份:
    2017
  • 资助金额:
    $ 29.49万
  • 项目类别:
Striatal Connectivity and Clinical Outcome in Psychosis
纹状体连接性和精神病的临床结果
  • 批准号:
    9920775
  • 财政年份:
    2016
  • 资助金额:
    $ 29.49万
  • 项目类别:
Striatal Connectivity and Clinical Outcome in Psychosis
纹状体连接性和精神病的临床结果
  • 批准号:
    9331735
  • 财政年份:
    2016
  • 资助金额:
    $ 29.49万
  • 项目类别:
2/3-Social Processes Initiative in Neurobiology of the Schizophrenia(s)
2/3-精神分裂症神经生物学社会过程倡议
  • 批准号:
    9110619
  • 财政年份:
    2014
  • 资助金额:
    $ 29.49万
  • 项目类别:
2/3-Social Processes Initiative in Neurobiology of the Schizophrenia(s)
2/3-精神分裂症神经生物学社会过程倡议
  • 批准号:
    8890889
  • 财政年份:
    2014
  • 资助金额:
    $ 29.49万
  • 项目类别:
2/3-Social Processes Initiative in Neurobiology of the Schizophrenia(s)
2/3-精神分裂症神经生物学社会过程倡议
  • 批准号:
    8758171
  • 财政年份:
    2014
  • 资助金额:
    $ 29.49万
  • 项目类别:
The Ninth Annual Pharmacogenetics in Psychiatry Meeting
第九届精神病学药物遗传学年会
  • 批准号:
    8055024
  • 财政年份:
    2010
  • 资助金额:
    $ 29.49万
  • 项目类别:

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