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Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension

Information source: Vanderbilt University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Orthostatic Hypotension; Pure Autonomic Failure; Multiple System Atrophy; Parkinson's Disease

Phase: N/A

Status: Active, not recruiting

Sponsored by: Vanderbilt University

Official(s) and/or principal investigator(s):
Italo Biaggioni, MD, Principal Investigator, Affiliation: Vanderbilt University

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.

Clinical Details

Official title: Norepinephrine Transporter Blockade as a Pathophysiological Biomarker in Neurogenic Orthostatic Hypotension

Study design: Time Perspective: Prospective

Primary outcome: Final Diagnosis (pre vs post ganglionic autonomic failure) based on clinical criteria.

Detailed description: This is an observational, prospective three-year longitudinal study. The investigators will enroll participants with primary neurogenic orthostatic hypotension. All participants will undergo an extensive neurological and cardiovascular evaluation, including detailed autonomic testing and quality of life assessment. The investigators will then determine the magnitude of the pressor effect produced by 18 mg atomoxetine given orally, measured 1 hour after drug administration. Participants will be followed annually or more often if there is a significant change in their clinical condition. During follow up at year 3, the investigators will repeat the initial neurological, cardiovascular and autonomic evaluation. The primary endpoint would be the final diagnosis made at year 3 after the initial evaluation (at the end of the follow-up period) or if they develop significant worsening of symptoms during follow-up phone assessments, based on specific clinical criteria.

Eligibility

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Locations and Contacts

Beth Israel Deaconess Medical Center (Harvard), Boston, Massachusetts 02215, United States

Mayo Clinic, Rochester, Minnesota 55902, United States

New York University, New York, New York 10016, United States

Vanderbilt University, Nashville, Tennessee 37232, United States

Additional Information

Vanderbilt University Autonomic Dysfunction Center

Beth Israel Deaconess Medical Center Department of Neurology

New York University Dysautonomia Center

Related publications:

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.

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.

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. Review.

Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr 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.

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.

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.

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.

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.

Starting date: March 2011
Last updated: May 27, 2014

Page last updated: August 23, 2015

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