Stellate Ganglion Blockade for the Management of Vasomotor Symptoms

星状神经节阻滞治疗血管舒缩症状

• 批准号: 9030718
• 负责人: DAVID R WALEGA
• 金额: $ 66.61万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9030718
• 关键词: Adverse effects; Affect; Aftercare; Ambulatory Monitoring; Amygdaloid structure; Anatomy; Anterior; Anxiety; Area; Blood Vessels; Brain; Brain region; Bupivacaine; Cervical spine; Clinical Trials; Controlled Clinical Trials; Effectiveness; Emotions; Fluoroscopy; Frequencies; Galvanic Skin Response; Ganglia; Hippocampus (Brain); Hot flushes; Hyperhidrosis disorder; Injection of therapeutic agent; Insula of Reil; Intervention; Intervention Studies; Ipsilateral; Local Anesthetics; Measures; Memory; Menopause; Monitor; Moods; Neck; Nerve; Nervous System Physiology; Neuropathy; Night Sweating; Outcome; Pain management; Paroxetine; Participant; Patient Self-Report; Performance; Physiological; Placebos; Postmenopause; Prefrontal Cortex; Process; Productivity; Publishing; Quality of life; Randomized; Relapse; Reporting; Research; Rest; Safety; Saline; Selective Serotonin Reuptake Inhibitor; Serious Adverse Event; Site; Skin; Sleep; Sleep disturbances; Structure; Structure of stellate ganglion; Subcutaneous Tissue; Sympathetic Nervous System; Symptoms; Techniques; Telemetry; Tissues; United States; United States Food and Drug Administration; Vascular Diseases; Vasomotor; Woman; Women' s Health; Work; active control; anxiety symptoms; arm; associated symptom; cognitive function; control trial; depressive symptoms; disturbance in affect; experience; hormone therapy; improved; innovation; mood symptom; neural circuit; neuroimaging; novel strategies; open label; painful neuropathy; public health relevance; relating to nervous system; secondary outcome; sleep regulation; support network; symptom treatment; symptomatic improvement; treatment effect; trend

 DESCRIPTION (provided by applicant): The overall aim of this randomized, sham-controlled clinical trial is to demonstrate that stellate ganglion block (SGB) is an effective and safe non-hormonal intervention for women seeking relief from vasomotor symptoms (VMS) and to identify the physiologic mechanisms underlying this treatment effect. More than 50% of women experience frequent hot flashes and night sweats (i.e., VMS), and these symptoms last on average 7.4 years. VMS are associated with decreased quality of life, increased depressive and anxiety symptoms, sleep disturbance, memory difficulties, and reduced productivity. Safety concerns raised in the Women's Health Initiative (WHI) led to an 80% decline in the use of hormone therapy in the United States. Identifying safe and effective non-hormonal treatments for VMS remains a priority in women's health research. The stellate ganglion, a sympathetic neural structure in the deep tissues of the neck, is commonly blocked with local anesthetics in the treatment of neuropathic and vascular disorders. In open-label intervention studies SGB with local anesthetic reduced VMS by 34 to 90% four weeks to several months after treatment. We conducted the first randomized, sham-controlled (injection of saline into subcutaneous tissue in the neck) trial of SGB (with 0.5% bupivacaine 5 mL) for the treatment of VMS in menopausal women with moderate to very severe VMS (n = 40). A single SGB with local anesthetic significantly reduced moderate-to-very severe VMS by 50% more than sham treatment and lasted for up to sixth months. Analyses of secondary outcomes revealed significant improvements in objectively-measured VMS and trends (p < .10) for improvements in depressive symptoms and memory performance with active SGB compared to sham intervention. In this proposal, we aim to conduct a randomized, sham-controlled clinical trial to more definitively assess the effects of SGB on VMS and to conduct foundational studies to identify the mechanisms of SGB action. The clinical trial will include 220 menopausal women who report 28 or more weekly VMS. Secondary outcomes will include objectively- measured VMS, mood and anxiety, quality of life, sleep, and memory performance. After an initial baseline assessment, women will be reassessed at 3 and 6 months following the SGB or sham intervention. In a subset of 60 women (30 per arm), we will perform a nested, mechanistic substudy built on foundational work in neuroimaging of VMS and ambulatory monitoring of sympathetic nerve activity and telemetry. These two mechanistic outcomes will be obtained at baseline and at 3 months following the intervention. We predict that compared to sham intervention, SGB will reduce the frequency of VMS, improve mood and anxiety, increase quality of life, and improve memory, reduce efferent sympathetic nerve activity and normalize brain activity in thermoregulatory brain areas but have no effect on sleep or other cognitive functions. By providing a more definitive understanding of the effectiveness of SGB, possible secondary benefits, and mechanisms of action, these findings will fill a critical gap in treatment options available to women.

 描述（由申请人提供）：这项随机、假对照临床试验的总体目的是证明星状神经节阻滞（SGB）是寻求缓解血管痉挛症状（VMS）的女性的有效和安全的非激素干预措施，并确定这种治疗效果的生理机制。超过50%的女性经常出现潮热和盗汗（即，这些症状平均持续7.4年。VMS与生活质量下降，抑郁和焦虑症状增加，睡眠障碍，记忆困难和生产力下降有关。妇女健康倡议（WHI）提出的安全问题导致美国激素治疗的使用下降了80%。确定安全有效的非激素治疗VMS仍然是妇女健康研究的优先事项。星状神经节是颈部深部组织中的交感神经结构，在神经病和血管疾病的治疗中通常用局部麻醉剂阻断。在开放标签干预研究中，局部麻醉的SGB在治疗后4周至数月将VMS降低了34%至90%。我们进行了第一项随机、假对照（向颈部皮下组织注射生理盐水）试验，即SGB（含0.5%布比卡因5 mL）治疗中度至极重度VMS的绝经期女性VMS（n = 40）。与假手术治疗相比，单次局部麻醉SGB可显著降低中度至极重度VMS 50%，并持续长达6个月。次要结局分析显示，与假干预相比，主动SGB组客观测量的VMS和抑郁症状改善趋势（p <0.10）和记忆表现改善显著改善。在这项提案中，我们的目标是进行一项随机，假对照临床试验，以更明确地评估SGB对VMS的影响，并进行基础研究，以确定SGB的作用机制。该临床试验将包括220名绝经期妇女，她们每周报告28次或更多次VMS。次要结果将包括客观测量的VMS、情绪和焦虑、生活质量、睡眠和记忆表现。在初始基线评估后，将在SGB或假干预后3个月和6个月对女性进行重新评估。在60名女性（每组30名）的子集中，我们将进行一项嵌套的机械子研究，该研究建立在VMS神经成像和交感神经活动和遥测的动态监测的基础工作上。将在基线和干预后3个月获得这两个机制结局。我们预测，与假干预相比，SGB将降低VMS的频率，改善情绪和焦虑，提高生活质量，改善记忆，减少传出交感神经活动，使体温调节脑区的脑活动正常化，但对睡眠或其他认知功能没有影响。通过对SGB的有效性、可能的次要益处和作用机制提供更明确的理解，这些发现将填补女性可用治疗选择的关键空白。