Autonomic Rare Diseases Clinical Research Consortium

自主神经罕见疾病临床研究联盟

• 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
• 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

 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.