恩他卡朋与普拉克索治疗帕金森病非运动症状的效果:前瞻性随机对照研究

Efficacy of entacapone and pramipexole in treating non-motor symptoms of Parkinson’s disease: a prospective randomized controlled trial

背景:帕金森病患者存在多种非运动症状,且这些症状研究影响患者的生活质量。恩他卡朋和普拉克索均可通过影响多巴胺代谢治疗帕金森病,但两者治疗帕金森病非运动症状的差异,目前尚不得而知。目的:比较恩他卡朋和普拉克索改善帕金森病非运动症状的效果的差异。方法:临床试验研究将在中国海口海南省老年病医院完成,为前瞻性随机对照研究,纳入388例原发性帕金森病患者,随机分为恩他卡朋组(n=194)和普拉克索组(n=194),分别接受恩他卡朋或普拉克索治疗。试验于2013-08-30经海南省老年病医院伦理审查委员会批准,批准号为伦审第S2013-038-01号。参与者对试验方案和过程均知情同意,并签署知情同意书。试验于2019-04-15在中国临床注册中心注册(注册号Chi CTR1900022534),注册方案版本号1.0。结果与结论:(1)主要结局指标设定为治疗后3周非运动症状改善率;(2)次要结局指标为治疗前以及治疗后3周能够反映炎症的血清中可溶性白介素2受体以及同型半胱氨酸水平和不良反应;(3)前期100例小样本自身对照的临床试验结果显示,恩他卡朋联合普拉克索治疗后患者体位性低血压、尿急尿频、性功能障碍、口感及流涎等自主神经症状,认知功能障碍、幻觉和抑郁焦虑等精神症状以及痉挛、疼痛及不安腿综合征等感觉异常指标的发生率均明显降低,同时患者血清中可溶性白介素2受体及同型半胱氨酸水平明显降低;(4)确认恩他卡朋与普拉克索治疗帕金森病非运动症状效果的优劣,将为未来临床治疗帕金森病非运动症状,改善患者生活质量提供帮助。

BACKGROUND: Individuals with Parkinson’s disease exhibit a variety of non-motor symptoms that can negatively impact quality of life. Although both entacapone and pramipexole can be used to treat Parkinson’s disease via modulation of dopamine metabolism, the ways in which these treatments differ in terms of their effects on the non-motor symptoms of Parkinson’s disease is unknown.OBJECTIVE: To compare the differences in treating the non-motor symptoms of Parkinson’s disease of entacapone and pramipexole.METHODS: This prospective, randomized, controlled trial will be conducted in the Geriatric Hospital of Hainan, Haikou, China. A total of 388 patients with idiopathic Parkinson’s disease will be randomly assigned to receive entacapone(n=194) or pramipexole(n=194). This study was approved by the Ethics Committee of the Geriatric Hospital of Hainan, China on August 30, 2013(approval number: S2013-038-01). Written informed consent regarding the study protocol and surgical procedure will be obtained from all participants. This study was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1900022534) on April 15, 2019. Protocol version: 1.0.RESULTS AND CONCLUSION:(1) The primary outcome measure will be the rate of improvement of non-motor symptoms 3 weeks after treatment.(2) Secondary outcome measures will be soluble interleukin-2 receptor and homocysteine levels in serum, which reflects inflammation, and adverse events before and 3 weeks after treatment.(3) Our self-controlled pilot study involving 100 patients showed that incidences of autonomic neurological symptoms such as postural hypotension, urinary urgency, urinary frequency, sexual dysfunction, dry mouth, and salivation, psychiatric symptoms such as cognitive dysfunction, hallucination, depression, and anxiety, and sensory abnormalities such as spasm, pain, and restless leg syndrome were remarkably reduced. Meanwhile, levels of serum soluble interleukin-2 receptor and homocysteine had noticeably decreased after treatment with entacapone and pramipexole.(4) This trial will confirm the efficacy of entacapone and pramipexole in the treatment of non-motor symptoms of Parkinson’s disease. We hope that our findings will provide direction for future clinical treatment of non-motor symptoms of Parkinson’s disease, leading to improved patient quality of life.