Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension (6103)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 |
- 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 |
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.
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| Contact: Italo Biaggioni, MD | 615-322-2931 | italo.biaggioni@vanderbilt.edu |
| Contact: Cyndya Shibao, MD | 615-322-2931 | cyndya.shibao@vanderbilt.edu |
| United States, Massachusetts | |
| Beth Israel Deaconess Medical Center (Harvard) | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Roy Freeman, MD 617-632-0899 prose1@bidmc.harvard.edu | |
| Contact: Christopher Gibbons, MD 617-632-0899 prose1@bidmc.harvard.edu | |
| Principal Investigator: Roy Freeman, MD | |
| Sub-Investigator: Christopher Gibbons, MD | |
| Sub-Investigator: Istvan Bonyhay, MD, PhD | |
| United States, Minnesota | |
| Mayo Clinic | Recruiting |
| Rochester, Minnesota, United States, 55902 | |
| Contact: Phillip Low, MD 507-284-3375 low@mayo.edu | |
| Contact: Peter O'Brien, PhD 507-284-3375 | |
| United States, New York | |
| New York University | Recruiting |
| New York, New York, United States, 10016 | |
| Contact: Horacio Kaufmann, MD 212-263-7041 horacio.kaufmann@nyumc.org | |
| Contact: Felicia Axelrod, MD 212-263-7041 felicia.axelrod@nyumc.org | |
| Principal Investigator: Horacio Kaufmann, MD | |
| Sub-Investigator: Felicia Axelrod, MD | |
| Sub-Investigator: Lucy Norcliff-Kaufmann, PhD | |
| Sub-Investigator: Alison Maloy, MD | |
| United States, Tennessee | |
| Vanderbilt University | Recruiting |
| Nashville, Tennessee, United States, 37232 | |
| Contact: Italo Biaggioni, MD 615-322-2931 italo.biaggioni@vanderbilt.edu | |
| Contact: Cyndya Shibao, MD 615-322-2931 cyndya.shibao@vanderbilt.edu | |
| Principal Investigator: Italo Biaggioni, MD | |
| Sub-Investigator: Cyndya Shibao, MD | |
| Sub-Investigator: David Robertson, MD | |
| Sub-Investigator: Satish Raj, MD | |
| Sub-Investigator: Amanda Peltier, MD | |
| Principal Investigator: Alfredo Gamboa, MD | |
| Sub-Investigator: Andre Diedrich, MD, PhD | |
| Sub-Investigator: Luis Okamoto, MD | |
| 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: | August 27, 2012 |
| 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:
|
Hypotension, Orthostatic Hypotension Parkinson Disease Multiple System Atrophy Shy-Drager Syndrome Atrophy Pure Autonomic Failure Vascular Diseases Cardiovascular Diseases Orthostatic Intolerance Primary Dysautonomias Autonomic Nervous System Diseases Nervous System Diseases Parkinsonian Disorders Basal Ganglia Diseases |
Brain Diseases Central Nervous System Diseases Movement Disorders Neurodegenerative Diseases Pathological Conditions, Anatomical Norepinephrine Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions Vasoconstrictor Agents Cardiovascular Agents Therapeutic Uses Adrenergic alpha-Agonists |
ClinicalTrials.gov processed this record on May 19, 2013