Purpose

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.

Condition

Eligibility

Eligible Ages
Between 40 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
placebo
placebo capsules
  • Drug: Atomoxetine
    norepinephrine transporter inhibitor
    Other names:
    • strattera
Active Comparator
atomoxetine
atomoxetine capsules 10 mg or 18 mg
  • Drug: Placebo
    placebo
    Other names:
    • non active medication

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Bonnie Black, RN III
615-343-6862
bonnie.black@vanderbilt.edu

More Details

NCT ID
NCT02784535
Status
Recruiting
Sponsor
Vanderbilt University Medical Center

Study Contact

Bonnie Black, RN
6153436862
bonnie.black@vanderbilt.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.