{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:04:43Z","timestamp":1787882683930,"version":"build-2784847793"},"reference-count":98,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"DOI":"10.13039\/100001594","name":"Familial Dysautonomia Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001594","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["U54NS065736"],"award-info":[{"award-number":["U54NS065736"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Neurol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurogenic orthostatic hypotension (nOH) is among the most debilitating nonmotor features of patients with Parkinson's disease (PD) and other synucleinopathies. Patients with PD and nOH generate more hospitalizations, make more emergency room visits, create more telephone calls\/mails to doctors, and have earlier mortality than those with PD but without nOH. Overall, the health-related cost in patients with PD and OH is 2.5-fold higher compared with patients with PD without OH. Hence, developing effective therapies for nOH should be a research priority. In the last few decades, improved understanding of the pathophysiology of nOH has led to the identification of therapeutic targets and the development and approval of two drugs, midodrine and droxidopa. More effective and safer therapies, however, are still needed, particularly agents that could selectively increase blood pressure only in the standing position because supine hypertension is the main limitation of available drugs. Here we review the design and conduct of nOH clinical trials in patients with PD and other synucleinopathies, summarize the results of the most recently completed and ongoing trials, and discuss challenges, bottlenecks, and potential remedies.<\/jats:p>","DOI":"10.1055\/s-0040-1713846","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T23:03:41Z","timestamp":1599692621000},"page":"523-539","source":"Crossref","is-referenced-by-count":16,"title":["Clinical Trials for Neurogenic Orthostatic Hypotension: A Comprehensive Review of Endpoints, Pitfalls, and Challenges"],"prefix":"10.1055","volume":"40","author":[{"given":"Jose-Alberto","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dysautonomia Center, New York University School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horacio","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dysautonomia Center, New York University School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/ana.24877","article-title":"Natural history of pure autonomic failure: a United States prospective cohort","volume":"81","author":"H Kaufmann","year":"2017","journal-title":"Ann Neurol"},{"issue":"12","key":"ref2","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/mds.26431","article-title":"MDS research criteria for prodromal Parkinson's disease","volume":"30","author":"D Berg","year":"2015","journal-title":"Mov Disord"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10286-011-0119-5","article-title":"Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome","volume":"21","author":"R Freeman","year":"2011","journal-title":"Clin Auton Res"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0002-9343(99)00425-8","article-title":"The association between orthostatic hypotension and recurrent falls in nursing home residents","volume":"108","author":"W L Ooi","year":"2000","journal-title":"Am J Med"},{"issue":"07","key":"ref5","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1001\/archinte.1990.00390190152026","article-title":"Hypotensive responses to common daily activities in institutionalized elderly. 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