Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension

NCT01316666 | Completed

• 2 other identifiers: 101311U54NS065736
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

The autonomic or automatic nervous system helps control blood pressure. Diseases of the autonomic nervous system may result in a drop in blood pressure on standing in many cases leading to fainting. Diseases that affect the autonomic nervous system include pure autonomic failure, multiple system atrophy and Parkinson's disease, and can present with very similar symptoms and it is sometimes difficult to determine an exact diagnosis. The purpose of the study is to find out if the blood pressure response from taking a single dose of the medication atomoxetine can help in the diagnosis of these diseases.

Conditions

Orthostatic Hypotension; Pure Autonomic Failure; Multiple System Atrophy; Parkinson's Disease

Keywords

orthostatic hypotension; Multiple System Atrophy; Pure Autonomic Failure; Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Final Diagnosis (pre vs post ganglionic autonomic failure) based on clinical criteria.

  Probable MSA - PAF with urinary incontinence or an orthostatic decrease of 30 mmHG in systolic blood pressure within 3 minutes of standing and poorly levodopa responsive parkinsonism or a cerebellar syndome. For Possible MSA - parkinsonism or a cerebellar syndrome and one additional feature. Probable PAF - orthostatic hypotension and impaired autonomic reflexes in the absence of clinical signs or symptoms of neurodegeneration. For Parkinson's Disease: diagnosed based on the United Kingdom Parkinson Disease Society Brain Bank clinical diagnostic criteria.

  3 years

Study Arms (1)

Neurogenic Hypotension

Patients with neurogenic hypotension, which includes those with Pure Autonomic Failure (PAF), Multiple System Atrophy (MSA) and Parkinson Disease (PD)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

participants with neurogenic orthostatic hypotension, which is a drop in systolic blood pressure of at least 30 mmHg within 5 minutes of standing with associated impaired autonomic reflexes.

You may qualify if:

• Age 18-80 years old with Neurogenic orthostatic hypotension, ≥30 mmHg drop in SBP within 5 minutes of standing
• Associated with impaired autonomic reflexes, as determined by absence of blood pressure overshoot during phase IV of the Valsalva maneuver
• Absence of other identifiable causes of autonomic neuropathy
• Able and willing to provide informed consent

You may not qualify if:

• Pregnancy
• Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance, and autoimmune neuropathies
• Known intolerance to atomoxetine, Pre-existing sustained severe hypertension (BP at least 180/110 mmHg in the sitting position)
• Clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months
• Any other significant systemic, hepatic, cardiac or renal illness
• Use of MAO-I within 14 days
• Known closed-angle glaucoma or Life-threatening arrhythmias

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (4)

Beth Israel Deaconess Medical Center (Harvard)

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

New York University

New York, New York, 10016, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (8)

• Birkenfeld AL, Schroeder C, Boschmann M, Tank J, Franke G, Luft FC, Biaggioni I, Sharma AM, Jordan J. Paradoxical effect of sibutramine on autonomic cardiovascular regulation. Circulation. 2002 Nov 5;106(19):2459-65. doi: 10.1161/01.cir.0000036370.31856.73.

  PMID: 12417543 BACKGROUND

• Esler MD, Wallin G, Dorward PK, Eisenhofer G, Westerman R, Meredith I, Lambert G, Cox HS, Jennings G. Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in humans. Am J Physiol. 1991 Apr;260(4 Pt 2):R817-23. doi: 10.1152/ajpregu.1991.260.4.R817.

  PMID: 2012253 BACKGROUND

• Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Klockgether T, Lang A, Lantos P, Litvan I, Mathias C, Oliver E, Robertson D, Schatz I, Wenning G. Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. Clin Auton Res. 1998 Dec;8(6):359-62. doi: 10.1007/BF02309628.

  PMID: 9869555 BACKGROUND

• Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008 Aug 26;71(9):670-6. doi: 10.1212/01.wnl.0000324625.00404.15.

  PMID: 18725592 BACKGROUND

• Goldstein DS, Holmes C. Metabolic fate of the sympathoneural imaging agent 6-[18F]fluorodopamine in humans. Clin Exp Hypertens. 1997 Jan-Feb;19(1-2):155-61. doi: 10.3109/10641969709080812.

  PMID: 9028643 BACKGROUND

• Goldstein DS, Polinsky RJ, Garty M, Robertson D, Brown RT, Biaggioni I, Stull R, Kopin IJ. Patterns of plasma levels of catechols in neurogenic orthostatic hypotension. Ann Neurol. 1989 Oct;26(4):558-63. doi: 10.1002/ana.410260410.

  PMID: 2510587 BACKGROUND

• Horimoto Y, Matsumoto M, Akatsu H, Ikari H, Kojima K, Yamamoto T, Otsuka Y, Ojika K, Ueda R, Kosaka K. Autonomic dysfunctions in dementia with Lewy bodies. J Neurol. 2003 May;250(5):530-3. doi: 10.1007/s00415-003-1029-9.

  PMID: 12736730 BACKGROUND

• Kaufmann H, Nahm K, Purohit D, Wolfe D. Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies. Neurology. 2004 Sep 28;63(6):1093-5. doi: 10.1212/01.wnl.0000138500.73671.dc.

  PMID: 15452307 BACKGROUND

Related Links

• Beth Israel Deaconess Medical Center Department of Neurology

MeSH Terms

Conditions

Hypotension, Orthostatic; Pure Autonomic Failure; Multiple System Atrophy; Parkinson Disease

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinsonian Disorders

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 16, 2011
• Study Start: March 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 6, 2017

Record last verified: 2017-01

Locations

US (4)