Autonomic Rare Diseases Clinical Research Consortium

自主神经罕见疾病临床研究联盟

基本信息

批准号：
9351568
负责人：
Italo Biaggioni
金额：
$ 125万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-15 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9351568
关键词：
Access to Information Address Adipose tissue Affect Agreement Autonomic nervous system Autonomic nervous system disorders Awareness Biological Markers Bladder Blood Vessels Characteristics Clinical Clinical Research Collaborations Community Outreach Conscious Data Development Diagnosis Diagnostic Disease Disease Progression Education Electric Capacitance Enrollment European Evaluation Failure Functional disorder Funding General Population Goals Growth Factor Heart Individual Injectable Intestines Investigational Therapies Israel Knowledge Lewy Body Dementia Link Measures Mesenchymal Stem Cells Multicenter Trials Multiple System Atrophy National Institute of Neurological Disorders and Stroke Natural History Nerve Nerve Degeneration Neurologic New York Norepinephrine Orthostatic Hypotension Palpitations Patient Care Patient Recruitments Patient-Centered Care Patients Peripheral Phenotype Physicians Pilot Projects Postural Orthostatic Tachycardia Syndrome Process Pure Autonomic Failures Quality of life Randomized Rare Diseases Recruitment Activity Regulation Research Research Personnel Residual state Rifampin Role Safety Schedule Scientist Site Specimen Standardization Stomach Support Groups Symptoms Testing Therapeutic Training Programs Universities Work alpha synuclein atomoxetine collaborative approach combat data management design disease diagnosis double-blind placebo controlled trial efficacy testing family support improved insight instrument member multidisciplinary novel novel therapeutics orthostatic intolerance patient advocacy group patient registry public health relevance reuptake synergism synucleinopathy tool virtual web site

项目摘要

DESCRIPTION (provided by applicant): This RDCRC on Rare Autonomic Diseases encompasses 5 major centers: Vanderbilt University, Mayo/Rochester, New York University, Beth Israel Deaconess/Harvard, and the NINDS/Clinical Center. Major support groups for autonomic disorders are engaged and participate. During the renewal period, our research efforts will focus on the rare autonomic diseases of multiple system atrophy (MSA), pure autonomic failure (PAF), and hyperadrenergic postural tachycardia syndrome (POTS), as well as dementia with Lewy bodies and other synucleinopathies. The overall objectives of our Consortium are to improve our understanding of the pathophysiology of these diseases to develop novel therapies to not only alleviate patients' symptoms but also to intervene in disease progression, and hopefully when possible to find a cure. Over the past four years, we met virtually all specific goals of our initial funding cycle. We developed a website that educates patients, researchers and clinicians, and assists with recruitment for the various consortium studies. We enrolled 469 patients in the ongoing natural history study of neurogenic orthostatic hypotension (and a total of 656 in all projects). We met target enrollment ahead of schedule in a randomized, double-blind, placebo-controlled trial of rifampicin in patients with MSA. While rifampicin did not improve MSA, this study taught us much, providing valuable insights and strategies that have been incorporated into the design of the clinical projects in our renewal. We also completed enrollment in a proof-of-concept study to examine the role of norepinephrine reuptake blockade as both a diagnostic and therapeutic tool in patients with neurogenic orthostatic hypotension. For this renewal, in addition to continuing with an expanded phenotyping and natural history study, we propose three new clinical projects and three new pilot projects. A trial of mesenchymal stem cells is directed at combating the growth factor deficiency recently identified in MSA. Our studies suggest that atomoxetine can improve orthostatic tolerance. We are proposing similar studies with reducing splanchnic capacitance in neurogenic orthostatic hypotension, harnessing residual sympathetic tone with 3,4- diaminopyridine in MSA and a novel vagal stimulation strategy in hyperadrenergic POTS. These studies will be linked with efforts to expand our development of autonomic biomarkers. Continuation of the Autonomic RDCRC will enable us to build on our recent new knowledge to understand and hopefully alter the course of these diseases. We will work collaboratively with patient advocacy groups. We will address informative biomarkers and elucidate mechanisms to find genuinely effective agents for the rare autonomic diseases.

描述（由申请人提供）：这个关于罕见自主神经疾病的 RDCRC 涵盖 5 个主要中心：范德比尔特大学、梅奥/罗切斯特、纽约大学、贝斯以色列女执事/哈佛大学和 NINDS/临床中心自主神经疾病的主要支持小组都参与其中。并参与更新期间，我们的研究工作将集中于多系统萎缩（MSA）、纯自主神经衰竭（PAF）和等罕见自主神经疾病。高肾上腺素能姿势性心动过速综合征 (POTS) 以及路易体痴呆和其他突触核蛋白病我们联盟的总体目标是提高我们对这些疾病的病理生理学的了解，以开发新的疗法，不仅可以缓解患者的症状，还可以改善患者的症状。干预疾病进展，并希望在可能的情况下找到治疗方法。在过去的四年里，我们几乎实现了最初资助周期的所有具体目标，并开发了一个网站来教育患者、研究人员和反对者。协助招募各种联合研究。我们招募了 469 名患者参加正在进行的神经源性直立性低血压自然史研究（所有项目总共招募了 656 名患者），我们在随机、双盲、安慰剂中提前达到了招募目标。 -利福平在 MSA 患者中的对照试验虽然利福平没有改善 MSA，但这项研究给了我们很多启发，提供了宝贵的见解和策略，这些见解和策略已纳入我们的临床项目设计中。我们还完成了一项概念验证研究的入组，以检验去甲肾上腺素再摄取阻断作为神经源性直立性低血压患者的诊断和治疗工具的作用。历史研究中，我们提出了三个新的临床项目和三个新的试点项目，旨在对抗最近在 MSA 中发现的生长因子缺乏症。我们正在提出类似的研究，包括降低神经源性直立性低血压的内脏容量，利用 MSA 中的 3,4-二氨基吡啶残余交感神经张力，以及在高肾上腺素能 POTS 中采用新型迷走神经刺激策略。这些研究将与扩大我们的开发工作相关。自主生物标志物的继续研究将使我们能够利用最近的新知识来理解并有望改变这些疾病的进程。我们将与患者倡导团体合作，研究信息丰富的生物标志物并阐明机制，以找到治疗罕见自主神经疾病的真正有效的药物。