1/2-Pramipexole in Bipolar Disorder: Targeting Cognition (PRAM-BD)

1/2-普拉克索治疗双相情感障碍：目标认知 (PRAM-BD)

• 批准号: 9070766
• 负责人: Katherine Elizabeth Burdick
• 金额: $ 11.79万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-23 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9070766
• 关键词: Activities of Daily Living; Address; Adverse effects; Affect; Affective Symptoms; Agonist; Antipsychotic Agents; Attention; Biological Neural Networks; Bipolar Disorder; Bipolar I; Clinical; Cognition; Cognitive; Cognitive deficits; Collaborations; Communities; Complex; Consensus; Data; Databases; Disease; Disease remission; Dopamine; Dopamine Agonists; Dose; Double-Blind Method; Ensure; Evaluation; Functional disorder; Future; Gambling; Health; Heterogeneity; Hospitals; Impaired cognition; Impairment; Intervention; Iowa; Label; Manic; Measures; Memory; Mental Depression; Modification; Mood Disorders; Moods; Neurocognition; Neurocognitive; Nootropic Agents; Outcome Measure; Paper; Parkinson Disease; Patient Monitoring; Patients; Performance; Persons; Pharmaceutical Preparations; Placebo Control; Placebos; Population; Quality of life; Randomized; Recording of previous events; Recovery; Reporting; Research Design; Research Personnel; Restless Legs Syndrome; Risk; Safety; Sample Size; Sampling; Schizophrenia; Severities; Signal Transduction; Site; Social Adjustment; Symptoms; Testing; Visit; Work; affective neuroscience; base; bipolar patients; clinically significant; cognitive control; cognitive enhancement; computerized; design; experience; follow-up; functional disability; improved; insight; medical schools; mood symptom; novel; pramipexol; primary outcome; response; reward processing; safety testing; skills; standard care; subthreshold depression; trial design; week trial

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，但大多数患者无法实现完全的发作间恢复，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，因为它们不能用标准的情绪稳定药物充分改善，并且它们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， 参加D2/D3激动剂普拉克索（Mirapex（c））的认知增强对照试验的双相情感障碍患者亚组。在进行这项先前的研究中，我们注意到几个重要的方法学限制和疾病相关的混淆，需要使用改良的方法进行随访，以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、连续性研究，以评价普拉克索对100例情感稳定的双相情感障碍患者神经认知功能的安全性和疗效。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来优化检测阳性信号的可能性：1）增加最大日剂量~ 2）纳入情感稳定且有认知障碍客观证据的患者~ 3）根据合并抗精神病药物治疗进行分层随机化~和4）将试验持续时间延长至6个月，以解决长期安全性问题， 有效性以及日常功能的潜在改善。 普拉克索已获美国FDA批准用于治疗帕金森病和不宁腿综合征。 在标签外应用中，我们将对100例稳定的I型双相情感障碍患者给予灵活剂量的普拉克索（1-3 mg/天）与安慰剂，持续24周。我们将在普拉克索给药前、第4周、第8周、第16周以及24周研究结束时，使用几种纸笔和计算机测试测量患者在注意力、记忆力和高阶认知任务方面的表现。此外，我们将包括几个新的情感神经科学为基础的措施，以深入了解普拉克索的影响与DA为基础的奖励处理相关的神经网络。最后，我们还将研究普拉克索对功能能力和社区功能指标的影响。 我们将密切监测患者的情绪症状的不可预见的变化，这些变化被认为是使他们处于发展躁狂或抑郁的风险中，并将在必要时停止试验。我们希望这项研究的结果将提供一个明确的去/不去的决定，关于追求这种药物作为一种认知增强剂在双相情感障碍。无论主要结果如何，我们预计这项试验将提供与情感障碍中基于D2/D3的奖励处理相关的其他重要数据。