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: 8760643
• 负责人: Katherine Elizabeth Burdick
• 金额: $ 38.14万
• 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 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8760643
• 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; Clinical Trials Design; 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; 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; Relative (related person); 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; clinically significant; cognitive control; cognitive enhancement; computerized; design; experience; follow-up; functional disability; improved; insight; medical schools; novel; pramipexol; primary outcome; public health relevance; response; reward processing; safety testing; skills; standard care; subthreshold depression; 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）：尽管治疗了双相情感障碍，但大多数患者仍未实现完全的表演间恢复和功能障碍。在相对缓解期间，许多患者继续患有神经认知功能障碍。这些疾病的持续特征代表了关键的治疗靶标，因为它们无法通过标准的情绪稳定药物得到充分的改善，并且与功能障碍和生活质量差有密切相关。在我们的小组的先前工作中（Burdick等，2012），我们报告了A中有明显疗效信号的初步证据 参加D2/D3激动剂Pramipexole（Mirapex（C））的受控认知增强试验的双极患者的子集。在进行先前的研究时，我们注意到了几种重要的方法论局限性和与疾病相关的混杂，这些混杂需要使用改良方法进行后续行动，以充分测试该药物在治疗双相情感障碍中认知功能障碍方面的安全性和功效。因此，我们提出了一项2个站点，合作的，24周，随机，安慰剂对照，辅助研究，以评估普拉米己核对100名情感性双极患者神经认知功能的安全性和功效。我们已经修改了先前试验的设计，以优化检测正面信号的可能性：1）增加最大的每日剂量〜2），包括有情地稳定的患者，具有与之认知障碍的客观证据〜3）基于与同时的抗精神治疗方法进行了更长的时间和4个月份的效力，以使其长期延长〜6） 疗效以及日常功能的潜在改善。 普拉米己烯已获得美国FDA批准帕金森氏病和不安的腿综合症。 在标签外应用中，我们将在24周内对100例稳定的双相情感障碍患者进行灵活剂量剂量的pramipexole（1-3 mg/day）与安慰剂相比。我们将在第4周，第8周，第16周，在24周的研究结束之前，使用多个纸笔和计算机测试来衡量患者在注意力，记忆和高阶认知任务上的表现。此外，我们还将包括一些新型的基于情感神经科学的措施，以深入了解普拉米克索对与基于DA的奖励处理相关的神经网络的影响。最后，我们还将研究普拉米克索对功能能力和社区功能衡量的影响。 我们将密切监测患者的情绪症状的不可预见的变化，这些变化被认为使他们面临躁狂或抑郁症的风险，并将在认为必要的情况下停止该试验。我们希望这项研究的发现将为追求该药物作为双相情感障碍的认知增强子提供明确的GO/No-Go/No-Go决定。无论主要结果如何，我们都希望该试验将提供与情感障碍中基于D2/D3的奖励处理有关的其他重要数据。