Thermoregulation and Cognition During Cool Ambient Exposure in Tetraplegia

NCT02379156 | Completed Phase 4 Results

• 3 other identifiers: HAN-14-04531569601589
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The ability to maintain normal core body temperature (Tcore = 98.6°F) is impaired in persons with a cervical spinal cord injury (tetraplegia). Despite the known deficits in the ability of persons with spinal cord injury (SCI) to maintain Tcore, and the effects of hypothermia to impair mental function in able-bodied (AB) persons, there has been no work to date addressing these issues in persons with tetraplegia. Primary Aim: To determine if exposure of up to 2 hours to cool temperatures (64°F) causes Tcore to decrease in persons with tetraplegia, and if that decrease is associated with a decrease in cognitive function. Primary Hypotheses: Based on our pilot data: (1) 66% of persons with tetraplegia and none of the matched controls will demonstrate a decline of 1.8°F in Tcore; (2) 80% of persons with tetraplegia and 30% of controls will have a decline of at least one T-score in Stroop Interference scores (a measure of executive function). Secondary Aim: To determine the change in: (1) distal skin temperature, (2) metabolic rate, and (3) thermal sensitivity. Secondary Hypothesis: Persons with tetraplegia will have less of a percent change in average distal skin temperatures and metabolic rate, and report lower thermal sensitivity ratings compared with AB controls. Tertiary Aim: To determine if a 10 mg dose of an approved blood pressure-raising medicine (midodrine hydrochloride) will (1) reduce the decrease in Tcore and (2) prevent or delay the decline in cognitive performance in the group with tetraplegia compared to the exact same procedures performed on the day with no medicine (Visit 1) in that same group. Tertiary Hypothesis: Through administering a one-time dose of midodrine, the medicine-induced decreased blood flow to the skin will lessen the decline in Tcore and prevent or delay the associated decline in cognitive performance compared to the changes in Tcore and cognitive performance during cool temperature exposure without midodrine in the same group with tetraplegia.

Conditions

Tetraplegia; Hypothermia; Mild Cognitive Impairment

Keywords

Quadriplegia; Spinal Cord Injury; Body Temperature Regulation; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Change in Core Body Temperature

  We measured the effects of cool temperature (64°F) exposure, of up to 120 minutes, on the ability to maintain a constant Tcore (i.e., Tcore of 98.6°F) in all intervention arms.

  120 minutes

Secondary Outcomes (4)

• Percent Change in Cognitive Performance - Wechsler Adult Intelligence Scale 4th Edition (WAIS IV)

  120 minutes

• Change in Distal Skin Temperature (Tsk)

  120 minutes

• Percent Change in Microvascular Perfusion

  Up to 120 minutes

• Percent Change in Oxygen Consumption (VO2)

  Up to 120 minutes.

Study Arms (3)

Able-bodied Control Cool Temperature Exposure / No Drug

OTHER

Subjects are able-bodied (AB) persons, ages 18-65. AB participants were matched to the SCI group by age and gender. Procedure is exposure to cool temperature (64° F) for up to 2 hours in a temperature-controlled room in order to assess the body's temperature-regulating mechanisms and any associated change in cognitive performance (Visit 1).

Other: Cool Temperature

SCI Cool Temperature Exposure / No Drug

EXPERIMENTAL

Subjects are persons with tetraplegia: spinal cord lesion level C3 to T1, American Spinal Injury Association Impairment Scale (AIS) levels A and B, ages 18-65 years. Procedure is exposure to cool temperature (64° F) for up to 2 hours in a temperature-controlled room in order to assess the body's temperature-regulating mechanisms and any associated change in cognitive performance (Visit 1).

Other: Cool Temperature

SCI Cool Temperature Exposure with Drug

EXPERIMENTAL

Subjects are persons with tetraplegia who completed Visit 1 (no drug). Subjects are administered a 10 mg tablet of midodrine hydrochloride by a physician before being exposed to cool temperature (64° F) for up to 2 hours in a temperature-controlled room in order to assess the body's temperature-regulating mechanisms and any associated change in cognitive performance (Visit 2).

Drug: Midodrine Hydrochloride; Other: Cool Temperature

Interventions

Midodrine Hydrochloride DRUG

Midodrine hydrochloride is an approved medication used to treat low blood pressure. We are using a standard dose of 10 mg (tablet) only one time to determine if the vascular-constricting effects of this drug will help keep warm blood closer to the body's core and improve the ability to maintain Tcore in a cool environment (off-label use). A physician will administer the drug once before the cool thermal challenge in subjects with tetraplegia only (Visit 2).

Also known as: Gutron, ProAmatine, Amatine, Orvaten, Midodrine hydrochloride 10 mg tablet

SCI Cool Temperature Exposure with Drug

Cool Temperature OTHER

Subjects will be exposed to a routinely encountered cool temperature (64° F) for up to to 2 hours depending on the vital signs (BP, HR, Tcore) and tolerance (comfort).

Also known as: 64° F

Able-bodied Control Cool Temperature Exposure / No Drug; SCI Cool Temperature Exposure / No Drug; SCI Cool Temperature Exposure with Drug

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Duration of SCI ≥1 year;
• Level of SCI C3-T1, AIS A \& B;
• Age between 18 and 68 years.

You may not qualify if:

• Evidence of sympathetic integrity below the lesion level by the skin axon-reflex vasodilatation (SkARV) test;
• Known allergies to midodrine hydrochloride;
• Past Medical History (PMH) of diagnosed heart, kidney, peripheral vascular, or cerebral vascular disease, or diabetes mellitus;
• Hypertension (BP\>140/90 mmHg);
• Untreated thyroid disease;
• Acute illness or infection;
• Current smoker;
• Pregnancy.

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center: lead
• The Craig H. Neilsen Foundation: collaborator

Study Sites (1)

Center of Excellence for the Medical Consequences of SCI, James J Peters VAMC

The Bronx, New York, 10468, United States

Location

Related Links

• Link to Research Center website. Look under Research tab to find Thermoregulation program.

MeSH Terms

Conditions

Quadriplegia; Hypothermia; Cognitive Dysfunction; Spinal Cord Injuries

Interventions

Midodrine; Tablets

Condition Hierarchy (Ancestors)

Paralysis; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Temperature Changes; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Spinal Cord Diseases; Central Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: John P. Handrakis
• Organization: James J. Peters VA Medical Center

John.Handrakis@va.gov

718-584-9000

Study Officials

• John P Handrakis, PT, DPT, EdD

  James J. Peters VAMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Health Science Specialist

Study Record Dates

• First Submitted: February 26, 2015
• First Posted: March 4, 2015
• Study Start: April 1, 2015
• Primary Completion: July 1, 2021
• Study Completion: December 1, 2022
• Last Updated: March 21, 2025
• Results First Posted: March 21, 2025

Record last verified: 2025-03

Locations

US (1)