Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure

NCT02897063 | Recruiting Phase 1

• 1 other identifier: 160255
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn more about the effects of midodrine and droxidopa, two medications used for the treatment of orthostatic hypotension (low blood pressure on standing), on the veins of the abdomen of patients with autonomic failure. The study will be conducted at Vanderbilt University Medical Center, and consists of 2 parts: a screening and 2 testing days. The total length of the study will be about 5 days. About 34 participants will be screened for the study.

Conditions

Autonomic Failure; Pure Autonomic Failure; Multiple System Atrophy; Parkinson Disease; Orthostatic Hypotension

Keywords

midodrine; droxidopa; splanchnic circulation

Outcome Measures

Primary Outcomes (1)

• Stroke volume

  The primary outcome will be the percent change from supine in stroke volume during HUT

  Up to 10 min of head up tilt

Study Arms (2)

Droxidopa and Placebo

EXPERIMENTAL

Patients will be studied on two separate days, two days apart: one day with the active drug and one day with placebo. The order of the study days will be randomized. On each study day, patients will receive a single oral dose of either droxidopa 300 mg or placebo after the first tilt table test, followed two hours later by a single oral dose of placebo.

Drug: Droxidopa; Drug: Placebo

Midodrine and Placebo

EXPERIMENTAL

Patients will be studied on two separate days, two days apart: one day with the active drug and one day with placebo. The order of the study days will be randomized. On each study day, patients will receive a single oral dose of placebo after the first tilt table test, followed two hours later by a single oral dose of either midodrine 10 mg or placebo.

Drug: Midodrine; Drug: Placebo

Interventions

Droxidopa DRUG

Single oral dose 300 mg

Also known as: Northera

Droxidopa and Placebo

Midodrine DRUG

Single oral dose 10 mg

Midodrine and Placebo

Placebo DRUG

sugar pill

Droxidopa and Placebo; Midodrine and Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects, age 40-80 years with possible or probable Multiple System Atrophy, Pure Autonomic Failure, or Parkinson disease, as defined by Consensus Criteria.
• 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.
• Subjects able and willing to provide informed consent.

You may not qualify if:

• Supine hypertension, defined as systolic blood pressure of ≥ 160 mmHg measured on two separate occasions.
• Pregnancy.
• Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathies, and autoimmune neuropathies.
• History of known aortic aneurisms, thoracic, abdominal or pelvic surgery in the past 6 months.
• Symptomatic abdominal or inguinal hernias.
• Severe gastroesophageal reflux.
• Recent fractures or fissures of ribs, thoracic or lumbar spine.
• Medical devices implanted on the abdominal wall or abdomen that would interfere with the abdominal compression.
• Intolerance to any increase in intraabdominal pressure.
• Clinically unstable coronary artery disease or major cardiovascular or neurological event in the past 6 months, and other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Autonomic Dysfunction Center/ Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Pure Autonomic Failure; Multiple System Atrophy; Parkinson Disease; Hypotension, Orthostatic

Interventions

Droxidopa; Midodrine

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinsonian Disorders; Orthostatic Intolerance; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Ethanolamines; Amino Alcohols; Alcohols

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bonnie K Black, RN

CONTACT

615-343-6862; autonomics@vumc.org

Luis E Okamoto, MD

CONTACT

615-936-6119; autonomics@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 12, 2016
• Study Start: September 1, 2016
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)