Recruiting

Observational Study

Sponsor:

Vanderbilt University Medical Center

Code:

NCT04782830

Conditions

Orthostatic; Hypotension, Neurogenic

Autonomic Failure

Pure Autonomic Failure

Multiple System Atrophy

Orthostatic; Hypotension, Parkinsonism

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Interventions

Accelerometer

placebo pill

Midodrine or atomoxetine pill

Study Details

Brief summary:

The objective of this study is to find a more objective and accurate way to assess the efficacy of the treatment for neurogenic orthostatic hypotension. For this purpose, the investigators will use an activity monitor to determine the amount of time patients spend in the upright position (standing and walking; upright time) during 1 week of placebo (a pill with no active ingredients) and 1 week of their regular medication for orthostatic hypotension (midodrine or atomoxetine at their usual doses). Total upright time (i.e. tolerance to standing and walking) will be compared between placebo and active treatment to test the hypothesis that it can be used to assess the efficacy of the treatment for orthostatic hypotension and whether this outcome is superior to the assessment of symptoms using validated questionnaires.

Conditions

Orthostatic; Hypotension, Neurogenic

Autonomic Failure

Pure Autonomic Failure

Multiple System Atrophy

Orthostatic; Hypotension, Parkinsonism

Study ID

NCT04782830

Start date

Feb 5, 2021

Status verified date

Jun, 2026

Completion date

Oct 1, 2027

Anticipated

Primary completion date

Jun 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Male and female subjects, age 40-80 years.
  • Possible or probable Multiple Systems Atrophy, Pure Autonomic Failure, or Parkinson's disease with neurogenic orthostatic hypotension.
  • Neurogenic orthostatic hypotension defined as a ≥ 30 mmHg decrease in systolic blood pressure within 3 minutes of standing associated with impaired autonomic reflexes determined by autonomic testing in the absence of other identifiable causes.
  • Patients on treatment for neurogenic orthostatic hypotension with either midodrine or atomoxetine, who have experienced some improvement in their orthostatic symptoms, but still remain symptomatic (Orthostatic hypotension symptom assessment \[OHSA\] score of 1 to 5 while on medication).
  • Patients who are able to stay with their caregiver during study participation.
  • Able and willing to provide informed consent.

Exclusion Criteria:

  • Bedridden, physically disabled, or unable to walk.
  • Patients with Orthostatic hypotension symptom assessment (OHSA) score ≥ 6, or orthostatic systolic blood pressure drop ≥ 30 mmHg on their regular treatment.
  • Patients taking more than one medication for the treatment of neurogenic orthostatic hypotension (concomitant use of pyridostigmine or fludrocortisone are accepted).
  • Pregnancy
  • Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies.
  • Clinically unstable coronary artery disease (recurrent angina despite medical therapy), or major cardiovascular or neurological event in the past 6 months (myocardial infarction, stroke).
  • Concomitant use of anticoagulants.

Study Design

Enrollment

29 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: placebo

Placebo pill will be taken for 7 days at the same frequency as their regular treatment with either midodrine or atomoxetine.

active comparator: Standard treatment

Either midodrine or atomoxetine at their regular dose.

Interventions

Accelerometer

A uniaxial accelerometer-based activity monitor (ActivpalTM) will be worn by participants on one of the thighs during the 7 days of the placebo and treatment periods.

placebo pill

Placebo pill will be taken for 7 days at the same frequency as their regular treatment with either midodrine or atomoxetine.

Midodrine or atomoxetine pill

Either midodrine or atomoxetine at their regular dose.

Primary outcome measure

  • Total standing time measured by an accelerometer [ Time Frame: 7 days of the treatment or placebo period ]
  • Orthostatic symptoms [ Time Frame: 7 days of treatment or placebo period ]

Central Contacts and Locations

Central contacts

Bonnie K Black, RN

615-343-6862autonomics@vumc.org

Locations

Autonomic Dysfunction Center/ Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Emily C Smith, RN MPH

615.875.1516autonomics@vumc.org

Bonnie K Black, RN

615-322-3304autonomics@vumc.org

Principal Investigator:

Italo Biaggioni, MD

More Information

Sponsor

Vanderbilt University Medical Center

Last update posted

Jul 2, 2026

Last verified

Jun, 2026

Keywords

  • orthostatic hypotension
  • autonomic failure
  • accelerometer
  • orthostatic symptoms

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vanderbilt University Medical Center on 2026-07-02.