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

NCT ID: NCT02307565

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2019-12-31

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.

Detailed Description

Acute Study:The purpose of this research study is to measure a spinal cord injured individual's blood pressure and blood flow to the brain at rest and during thinking tasks before and after a single dose of midodrine, a drug used to treat low blood pressure (10 mg). Eligible participants will complete 2 visits to the laboratory. Visit 1, the subject will be given midodrine and Visit 2, the subject will be given a placebo. The order of the drug is random.

Observational Study:The purpose of this research study is to determine how blood pressure changes throughout the day in a spinal cord injured individual. There is no drug in this study. This study will last about 1 month and the subject will visit the laboratory 2 times, at the beginning and at the end of the month. The subject will be given a blood pressure monitor and will be asked to record his/her blood pressure at least 3 times a day. The laboratory visits will involve the participant discussing his/her monthly blood pressure recordings and experience with blood pressure monitor.

30-Day Crossover Study: The purpose of this research study is to determine the safety and efficacy of midodrine administration over a 30-day period of time. 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 subject's participation will involve about 10 weeks and the subject will be asked to visit the laboratory 8 times. The subject will be asked to take midodrine for the first 30 days and after the 14 day washout period, the subject will be asked to take a placebo for 30 days. The order of the drug will be random. The subject and the study investigators will not know which drug the subject is receiving first and second during the 30 day-treatment phase. For visit 1,4, 5 and 8(Initial visits-start of new drug administration and Post Visits- end of new drug administration), the subject will complete many different thinking tasks while his/her blood pressure, heart rate and cerebral blood flow is taken. The subject will also complete quality of life surveys, autonomic dysreflexia surveys, and will take home a blood pressure monitor to continue to monitor blood pressure. For visit 2, 3, 6, and 7, the subject's blood pressure, cerebral blood flow and heart rate will be measured. Subject will also complete the autonomic dysreflexia survey.

30-Day Crossover & MRI/Functional MRI (fMRI) Study: Eligible participants will in addition to completing the 30-Day Crossover study (procedure explained above), will also complete a MRI/fMRI Visit 1, 4, and 8.

Conditions

Spinal Cord Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Midodrine

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

Group Type: EXPERIMENTAL

Midodrine

Intervention Type: 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.

Placebo

Intervention Type: 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.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Midodrine

Intervention Type: 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.

Placebo

Intervention Type: 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.

Interventions

Midodrine

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Midodrine or Placebo; Midodrine or Placebo

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kessler Foundation

OTHER

Sponsor Role: collaborator

James J. Peters Veterans Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

Jill M. Wecht, Ed.D.

Research Health Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jill M Wecht, Ed.D

Role: PRINCIPAL_INVESTIGATOR

JJPVAMC

Trevor Dyson-Hudson, MD

Role: PRINCIPAL_INVESTIGATOR

Kessler Foundation

Locations

Kessler Foundation Research Center

West Orange, New Jersey, United States

James J Peters VAMC

The Bronx, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33177997 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32203065 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

WEC-13-066

Identifier Type: -

Identifier Source: org_study_id