Treatment of Post-SCI Hypotension

Treatment of Post-SCI Hypotension: A Randomized Controlled Study of Usual Care Versus Anti Hypotension Therapy

While treatment strategies for OH have been identified for use in persons with acute SCI, the field of SCI medicine lacks a gold standard for treatment thresholds and well-defined outcome parameters. Comprehensively documenting the impact of orthostatic hypotension (OH), regardless of symptoms, during acute rehabilitation and identifying the effects of two different treatment approaches on therapy participation and adherence to an intended rehabilitation plan could have a significant impact on clinical practice in the acute rehabilitation setting following SCI.

Study Overview

• Status: Completed
• Conditions: Cerebral Blood Flow; Blood Pressure; Hypotension; Orthostatic Hypotension; Spinal Cord Injury; Autonomic Dysreflexia; Baroreceptor Integrity; Sympathetic Integrity; Vagal Integrity; Venous Occlusion Plethysmography
• Intervention / Treatment: Drug: Midodrine Hydrochloride

Detailed Description

Baseline Testing: Subjects will visit the testing laboratory on the SCI Rehabilitation Unit for baseline data collection, prior to initiation of the treatment protocol. Upon arrival, subjects will be placed in the supine position on an adjustable surface for instrumentation, which will be conducted in a quiet, dimly lit, thermo-neutral testing environment. After a 20-minute period of quiet rest, a 10-minute sample of supine heart rate (HR), respiratory rate, BP and CBF velocity data will be collected. Venous occlusion plethysmography (Vop) will be collected in the supine position for two 5-minute periods. After the supine data collection, subjects will be passively moved into the seated position, with the knees and hips at 90°, for the 10-minute seated data collection period. Subjects will be asked to complete two surveys related to AD and OH symptomology. Finally, subjects will be fitted with a 24-hour HR and BP monitor and will be asked to go about their normal routine. A record of all daily activities including rehabilitation, medications, eating and sleep/wake times will be logged. This testing session should take approximately 1 hour.

Daily Testing: Every day supine and seated BP measurements will be performed at least three times per day. These BP assessments will be recorded in the supine and seated positions in the subject's room by a patient care associate who is blind to the study arm allocation. For every scheduled physical and occupational therapy session, the treating therapist will be asked to complete a brief 6 question survey to document if that session was altered, disrupted, or missed due to hypotension (Therapist Reported Version). The subject will also be asked to complete a brief survey to determine if from their perspective the session was altered, disrupted or missed due to hypotension (Subject Reported Version). In addition, every day a co-investigator and the attending physician for that subject will complete an EMR review of queried BP values within the previous 24 hours, symptoms of low BP, adverse events related to high or low BP, and will review (and act upon for the usual care arm) the protocol treatment decision tree.

Weekly Testing: At weekly intervals of between 6 and 8 days, subjects will be asked to visit the testing laboratory on the SCI Rehabilitation Unit. Procedures for the weekly testing sessions will be the same as for the Baseline Testing. The 24-hour BP assessment will be conducted twice weekly.

Discharge Testing: At discharge subjects will undergo similar testing as described during the Baseline and Weekly Testing with the addition of the Patient Global Impression of Change survey, which will be administered by the Mount Sinai Site Research Assistant.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10468
      • VA Medical Center, Bronx
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Any level of injury;
• Any AIS grade of SCI;
• Non-ventilator dependent
• Primarily wheelchair dependent for mobility;
• Duration of injury < 1 year
• Systolic BP less than 110 mmHg and/or diastolic BP less than 70 mmHg for males.
• Systolic BP less than 100 mmHg and/or diastolic BP less than 70 mmHg for females
• Primary Language is English.
• Able to provide informed consent

Exclusion Criteria:

• Have insufficient mental capacity to independently provide informed consent
• Have insufficient English speaking or reading ability to provide informed consent or complete assessments in English
• Have contraindications to the use of midodrine hydrochloride
• Are pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Usual Care Group; Individuals randomized to the usual care group will receive BP management according to the usual care in current practice in the SCI Rehabilitation Unit. Will receive treatment only if they experience symptoms that are associated with low BP (dizziness, lightheadedness, nausea, blurry vision, loss of consciousness, etc.). Treatment to lessen or eliminate these symptoms of low blood pressure will be guided by the attending physician and can include physical countermeasures to increase blood pressure (abdominal binders, comperssion stockings, etc.) and/or midodrine .	Drug: Midodrine Hydrochloride; Level 1: Compression stockings, abdominal binder Level 2: Midodrine 5mg 2x/d Level 3: Midodrine 10mg 2x/d Level 4: Midodrine 15mg 2x/d Level 5: Midodrine 20mg 2x/d Level 6 Midodrine 20mg 2x/d and Fludrocortisone 0.1mg 2x/d Level 7 Midodrine 20mg 2x/d and Fludrocortisone 0.2mg 2x/d; Other Names: Midodrine
Experimental: BP Threshold Treatment Group; Individuals assigned to the BP threshold treatment group will receive BP management, regardless of symptoms, to maintain systolic BP between 111-135 mmHg for males and 101-135 mmHg for females for the duration of their in-patient hospital stay. This treatment will be started based on your low BP, regardless of if you experience symptoms that are associated with low BP (dizziness, lightheadedness, nausea, blurry vision, loss of consciousness, etc.). Before you start on any medication you will receive physical countermeasures to increase blood pressure (abdominal binders, comperssion stockings, etc.). If your blood pressure remains low after using these countermeasures you will begin to take midodrine 3 times a day as described in the intervention section. The dosage will increase and be stopped once until your seated SBP is between 111-135 mmHg.	Drug: Midodrine Hydrochloride; Level 1: Compression stockings, abdominal binder Level 2: Midodrine 5mg 2x/d Level 3: Midodrine 10mg 2x/d Level 4: Midodrine 15mg 2x/d Level 5: Midodrine 20mg 2x/d Level 6 Midodrine 20mg 2x/d and Fludrocortisone 0.1mg 2x/d Level 7 Midodrine 20mg 2x/d and Fludrocortisone 0.2mg 2x/d; Other Names: Midodrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Affected Therapy Sessions	Responses to the questions "was the therapy session affected by low BP or concern for low BP development?" between the usual care and BP threshold treatment groups. The percent of sessions with a "yes" response are reported.	Inpatient hospitalization (up to 4 months)
Systolic Blood Pressure	Systolic hypertension (>/= 140 mmHg)	Inpatient hospitalization (up to 4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure	Systolic hypotension (males: < 110 mmHg; females: < 100 mmHg)	Inpatient Hospitalizations (up to 4 months)
Missed Therapy Sessions	Percentages of missed therapy sessions, due to low BP or concern for low BP development, in the usual care and BP treatment groups	Inpatient Hospitalizations (up to 4 months)

Collaborators and Investigators

• Sponsor: James J. Peters Veterans Affairs Medical Center
• Collaborators: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Jill M Wecht, Ed.D., James J. Peters VA Medical Center

Publications and helpful links

General Publications

• Vaccaro DH, Weir JP, Noonavath M, Bryce TN, Escalon MX, Huang V, Delgado A, Wecht JM. Orthostatic systemic and cerebral hemodynamics in newly injured patients with spinal cord injury. Auton Neurosci. 2022 Jul;240:102973. doi: 10.1016/j.autneu.2022.102973. Epub 2022 Mar 18.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: September 22, 2016
• First Submitted That Met QC Criteria: September 27, 2016
• First Posted (Estimated): September 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Hypotension; Spinal Cord Injuries; Hypotension, Orthostatic; Autonomic Dysreflexia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: WEC-16-050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No