Blood Pressure, Cerebral Blood Flow and Cognition in Spinal Cord Injury

NCT02307565 | Completed Phase 3 Results

• 1 other identifier: WEC-13-066
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

Following spinal cord injury autonomic regulation of the cardiovascular system is impaired, which results in a variety of measurable abnormalities in blood pressure. Evidence of causality has been documented in the general medical literature with findings of improved cognitive function following acute increases in blood pressure using the anti-hypotensive agent Midodrine Hydrochloride (midodrine). Additionally, a recent report documented an inverse association between blood pressure and depression suggesting that low blood pressure may confer greater risk than high blood pressure. Midodrine is a drug approved by the Food and Drug Administration to treat low blood pressure in the general population. Midodrine is not approved in the United States to treat low blood pressure in persons with spinal cord injury. Therefore, its use in this study is investigational. The first objective is to characterize the relationship between blood pressure, cerebral blood flow velocity and cognitive function after a single dose of midodrine compared to placebo. Second objective is to determine the long-term safety and efficacy of midodrine administration.

Conditions

Spinal Cord Injury

Keywords

Midodrine; Blood pressure; Orthostatic hypotension; Spinal Cord Injury; Sympathetic vascular control; Cerebral blood flow velocity; Cognition function tasks; Quality of Life; MRI; fMRI

Outcome Measures

Primary Outcomes (1)

• Systolic Blood Pressure

  Seated systolic blood pressure following midodrine administration compared to placebo.

  30 days

Secondary Outcomes (3)

• Cerebral Blood Flow

  30 days

• Hopkins Verbal Learning Test

  30 days

• Number of Hypertensive Events

  30 days

Study Arms (2)

Midodrine

EXPERIMENTAL

Arm 1 last 30 days. Subject will either be given midodrine or placebo to take during Arm 1.

Drug: Midodrine; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Arm 2 is followed by a 14 day washout period. Arm 2 last 30 days. Subject will be given a drug (placebo or midodrine) to take during Arm 2.

Drug: Midodrine; Drug: Placebo

Interventions

Midodrine DRUG

Each arm (2) will last 30 days with a 14 day washout in between each arm. Subjects nor the investigators will know which drug (midodrine or placebo) is administered to the subject for the first arm (30 days) and the second arm (30 days). The subjects will take a pill three times a day. Each subject will return home with a blood pressure monitor and will be asked to report his/her blood pressure at least 3 times a day and complete questionnaires based on how he/she is feeling.

Also known as: Midodrine or Placebo

Midodrine; Placebo

Placebo DRUG

Each arm (2) will last 30 days with a 14 day washout in between each arm. Subjects nor the investigators will know which drug (midodrine or placebo) is administered to the subject for the first arm (30 days) and the second arm (30 days). The subjects will take a pill three times a day. Each subject will return home with a blood pressure monitor and will be asked to report his/her blood pressure at least 3 times a day and complete questionnaires based on how he/she is feeling.

Also known as: Midodrine or Placebo

Midodrine; Placebo

Eligibility Criteria

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

You may qualify if:

• Spinal Cord Injured
• Between the ages of 18-65 years old.
• Level of injury is between C1-T12
• Primarily wheelchair dependent for ambulation
• Have a spinal cord injury that is ASIA Impairment Scale (AIS) grade of A, B or C
• Injury occurred more than 1 year ago
• Low blood pressure (Systolic BP less than 110 mmHg for males, Systolic BP less than 100 mmHg for females)
• Primary language is English
• I am right handed

You may not qualify if:

• Currently have an illness or infection
• Severe history of AD (more than 3 symptomatic events per week, evidence of blood pressure elevations above 140/90 mmHg,significant adverse subjective symptoms reporting)
• Hypertension or diabetes
• History of Traumatic Brain Injury (TBI)
• Neurological condition other than SCI (Alzheimer's disease, dementia, stroke, multiple sclerosis, Parkinson's disease, etc.)
• History of epilepsy or other seizure disorder
• Diagnosis of a psychiatric disorder such as post-traumatic stress disorder, schizophrenia or bipolar disorder
• Within the past 6 months, abused illicit drugs
• Pre-screen mini mental status exam score of less than 24, as rated by the researcher
• Vision is impaired- more than 20/60 in worst eye (with prescription eyewear)
• Coronary heart and/or artery disease
• Major surgery in the last 30 days
• Pregnant

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center: lead
• Kessler Foundation: collaborator

Study Sites (2)

Kessler Foundation Research Center

West Orange, New Jersey, 07052, United States

Location

James J Peters VAMC

The Bronx, New York, 10468, United States

Location

Related Publications (2)

• Bloom O, Wecht JM, Legg Ditterline BE, Wang S, Ovechkin AV, Angeli CA, Arcese AA, Harkema SJ. Prolonged Targeted Cardiovascular Epidural Stimulation Improves Immunological Molecular Profile: A Case Report in Chronic Severe Spinal Cord Injury. Front Syst Neurosci. 2020 Oct 15;14:571011. doi: 10.3389/fnsys.2020.571011. eCollection 2020.

  PMID: 33177997 DERIVED

• Wecht JM, Weir JP, Katzelnick CG, Chiaravalloti ND, Kirshblum SC, Dyson-Hudson TA, Weber E, Bauman WA. Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI. Spinal Cord. 2020 Sep;58(9):959-969. doi: 10.1038/s41393-020-0448-0. Epub 2020 Mar 17.

  PMID: 32203065 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Hypotension, Orthostatic

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Dr. Jill Wecht
• Organization: James J Peters VAMC

jm.wecht@va.gov

718-584-9000

Study Officials

• Jill M Wecht, Ed.D

  JJPVAMC

  PRINCIPAL INVESTIGATOR

• Trevor Dyson-Hudson, MD

  Kessler Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Health Scientist

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: December 4, 2014
• Study Start: March 1, 2014
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 21, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-02

Locations

US (2)