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Trial record 1 of 7 for:    "Pure Autonomic Failure" | "Norepinephrine"
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Norepinephrine Transporter Blockade, Autonomic Failure (NETAF) (NETAF)

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ClinicalTrials.gov Identifier: NCT02784535
Recruitment Status : Recruiting
First Posted : May 27, 2016
Last Update Posted : August 21, 2019
Sponsor:
Collaborator:
NYU Langone Health
Information provided by (Responsible Party):
Cyndya Shibao, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE May 24, 2016
First Posted Date  ICMJE May 27, 2016
Last Update Posted Date August 21, 2019
Actual Study Start Date  ICMJE August 29, 2016
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 26, 2016)
Orthostatic Hypotension Questionnaire [ Time Frame: 2 weeks ]
Questionnaire that assess pre-syncopal symptoms
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02784535 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2016)
Blood pressure [ Time Frame: 2 weeks ]
blood pressure assessment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Norepinephrine Transporter Blockade, Autonomic Failure (NETAF)
Official Title  ICMJE Phase 2 Norepinephrine Transporter Blockade, Autonomic Failure IND117394 12/28/12
Brief Summary Drug therapy for patients suffering from autonomic failure and neurogenic orthostatic hypotension are scarce and not effective. If left untreated, these patients have the highest risk of syncope, falls and fall-related injuries. The proposed study will determine the clinical benefit of a commercially available drug, atomoxetine, to reduce symptoms associated with neurogenic orthostatic hypotension in patients with autonomic failure.
Detailed Description

Autonomic failure is a group of rare neurodegenerative disorders that primarily affect the autonomic nervous system. These patients develop neurogenic orthostatic hypotension (OH) because of impaired autonomic reflexes that control cardiovascular and neuro-humoral adaptation to upright posture. The treatment of neurogenic OH is challenging; the therapeutic options are scarce, and some patients are refractory to treatment.

Atomoxetine is a selective norepinephrine transporter inhibitor that increases the availability of norepinephrine in the synapse by blocking its reuptake. Our preliminary data in sixty-five patients with primary autonomic failure and neurogenic OH showed that atomoxetine was more effective than midodrine, standard of care, in improving standing SBP (+7.5 mm Hg). Notably, only atomoxetine and not midodrine induced a significant reduction in OH-related symptoms (lightheadedness and dizziness) compared with placebo. In this proposal, we will test the hypothesis that prolonged administration of the norepinephrine transporter blocker, atomoxetine, improves OH-related symptoms and OH-impact on daily activities compared with placebo in autonomic failure patients. We propose a randomized, double-blind, placebo-controlled, 2x2 crossover study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Neurogenic Orthostatic Hypotension
Intervention  ICMJE
  • Drug: Atomoxetine
    norepinephrine transporter inhibitor
    Other Name: strattera
  • Drug: Placebo
    placebo
    Other Name: non active medication
Study Arms  ICMJE
  • Placebo Comparator: placebo
    placebo capsules
    Intervention: Drug: Atomoxetine
  • Active Comparator: atomoxetine
    atomoxetine capsules 10 mg or 18 mg
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 26, 2016)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 40 years old or older
  • Neurogenic Orthostatic Hypotension (defined by a reduction of ≥20 mmHg drop in SBP within 3 minutes of standing, associated with impaired autonomic reflexes as assessed by autonomic function tests.

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Hypersensitivity to atomoxetine (severe allergic reaction, rash, urticaria, anaphylaxis)
  • Use of other norepinephrine transporter inhibitors such as Wellbutrin (Bupropion), Cymbalta (Duloxetine), Effexor (venlafaxine), Pristiq (desvenlafaxine), Savella (milnacipran)
  • Previous history (within 14 days prior to enrollment) and current use of monoamine oxidase inhibitors
  • Concomitant use of strong CYP2D6 inhibitors such as delavirdine, paroxetine, fluoxetine, quinidine
  • Pre-existing sustained severe hypertension (BP ≥ 140/80 mmhg in the sitting position)
  • Impaired hepatic function (aspartate amino transaminase [AST] and/or alanine amino transaminase [ALT] >2 x upper limit of normal range)
  • Impaired renal function (serum creatinine equal or more than 1.6 mg/dl)
  • Myocardial infarction within 6 months prior to enrollment
  • Congestive heart failure (LV hypertrophy acceptable)
  • History of serious neurologic disease such as cerebral hemorrhage, or stroke
  • Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, unlikelihood of completing the study, and mental conditions rendering the subject unable to understand the nature, scope, and possible consequences of the study
  • Narrow-angle glaucoma
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bonnie Black, RN 6153436862 bonnie.black@vanderbilt.edu
Contact: Jose Martinez 2122637225 Jose.Martinez@nyumc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02784535
Other Study ID Numbers  ICMJE 160415
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Cyndya Shibao, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE NYU Langone Health
Investigators  ICMJE
Principal Investigator: Cyndya A Shibao, MD Vanderbilt University Medical Center
Principal Investigator: Horacio Kaufmann, MD NYU Langone Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP