Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension (6103)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01316666
First received: March 15, 2011
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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.


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

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Norepinephrine Transporter Blockade as a Pathophysiological Biomarker in Neurogenic Orthostatic Hypotension

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Final Diagnosis (pre vs post ganglionic autonomic failure) based on clinical criteria. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 50
Study Start Date: March 2011
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Neurogenic Hypotension
Patients with neurogenic hypotension, which includes those with Pure Autonomic Failure (PAF), Multiple System Atrophy (MSA) and Parkinson Disease (PD)

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01316666

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center (Harvard)
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55902
United States, New York
New York University
New York, New York, United States, 10016
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Italo Biaggioni, MD Vanderbilt University
  More Information

Additional Information:
Publications:

Responsible Party: Italo Biaggioni, MD, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01316666     History of Changes
Other Study ID Numbers: 101311, U54NS065736
Study First Received: March 15, 2011
Last Updated: May 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
orthostatic hypotension
Multiple System Atrophy
Pure Autonomic Failure
Parkinson's Disease

Additional relevant MeSH terms:
Shy-Drager Syndrome
Parkinson Disease
Hypotension
Atrophy
Hypotension, Orthostatic
Multiple System Atrophy
Pure Autonomic Failure
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Norepinephrine
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents

ClinicalTrials.gov processed this record on September 16, 2014