Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension

Parkinson's Disease Clinical Trial

— 6103  

Official title:

Norepinephrine Transporter Blockade as a Pathophysiological Biomarker in Neurogenic Orthostatic Hypotension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01316666
• Other study ID #: 101311
• Secondary ID: U54NS065736
• Status: Completed
• Phase: N/A
• First received: March 15, 2011
• Last updated: January 4, 2017
• Start date: March 2011
• Est. completion date: December 2016

Study information

• Verified date: January 2017
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Atrophy
• Hypotension
• Hypotension, Orthostatic
• Multiple System Atrophy
• Orthostatic Hypotension
• Parkinson Disease
• Parkinson's Disease
• Pure Autonomic Failure
• Shy-Drager Syndrome

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center (Harvard)	Boston	Massachusetts
United States	Vanderbilt University	Nashville	Tennessee
United States	New York University	New York	New York
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No

External Links

•   Beth Israel Deaconess Medical Center Department of Neurology
•   New York University Dysautonomia Center
•   Vanderbilt University Autonomic Dysfunction Center