Body Temperature in Persons With Tetraplegia When Exposed to Cold
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|ClinicalTrials.gov Identifier: NCT01822535|
Recruitment Status : Completed
First Posted : April 2, 2013
Results First Posted : March 4, 2016
Last Update Posted : March 4, 2016
|First Submitted Date ICMJE||March 21, 2013|
|First Posted Date ICMJE||April 2, 2013|
|Results First Submitted Date||November 23, 2015|
|Results First Posted Date||March 4, 2016|
|Last Update Posted Date||March 4, 2016|
|Study Start Date ICMJE||July 2011|
|Actual Primary Completion Date||October 2015 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||Core body temperature [ Time Frame: 2 hours ]
We will test the effects of cool temperature (64°F) exposure, of up to 120 minutes, on the ability to maintain a constant body temperature (e.g., core temperature of 98.6°F) in persons with tetraplegia.
|Change History||Complete list of historical versions of study NCT01822535 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
||Cognitive performance [ Time Frame: 2 hours ]
Cognitive performance will be evaluated as a composite measure consisting of assessments of attention, working memory, processing speed and executive function. We will measure the change in cognitive performance in persons with tetraplegia after exposure to a cool environment (64°F) of up to 120 min in the seated position.
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Body Temperature in Persons With Tetraplegia When Exposed to Cold|
|Official Title ICMJE||Core Temperature During Cold Exposure in Persons With Tetraplegia|
The ability to maintain normal body core temperature (Tcore = 98.6°F) is impaired in persons with tetraplegia. Despite the known challenges to 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.
The aim of this study is to determine if exposure of up to 2 hrs to cool temperatures (64°F) causes body core temperature to decrease in persons with tetraplegia and if that decrease is related to a decrease in mental performance.
After sitting in a cool (64°F) room for up to 2 hours the investigators hypotheses are:
Hypotheses (1): Tcore of most of the persons with tetraplegia will decline approximately 1.8°F (e.g., 98.6 to 96.8°F) while Tcore of controls will not decline at all; (2) Most of the persons with tetraplegia will show a decline in mental performance (memory or clear-headedness) while only some of AB controls will show a decline.
The second aim of this study is to determine if a 10 mg dose of an approved blood pressure raising medicine (midodrine hydrochloride) will (1) reduce the decrease in body core temperature and (2) prevent or delay the decline in mental performance in the group with tetraplegia compared to the exact same procedures performed on the day with no medicine (Visit 1) in the same group.
Hypotheses (3 & 4): The changes in blood flow to the skin caused by taking a one-time dose of midodrine will lessen the decline in Tcore and prevent or delay the decline in mental performance compared to the changes in Tcore and mental performance during cool temperature exposure without midodrine in the group with tetraplegia.
This study will investigate the mechanisms contributing to the thermoregulatory fragility in persons with tetraplegia when exposed to cool ambient temperatures that are routinely encountered during activities of daily living (ADL). Subnormal body core temperatures and vulnerability to hypothermia (Tcore<95°F) has been reported in veterans with tetraplegia upon exposure to relatively mild environmental temperatures. The impact that a drift in Tcore will be expected to have on cognitive performance, specifically working memory and executive function, will be demonstrated. These 2 areas of cognitive performance are vital for the ability to optimally care for one's self, which persons with higher cord lesions must excel at to ensure health, as well as to be able to attain the maximal degree of independence possible. Administration of an alpha agonist, midodrine hydrochloride, in an attempt to attenuate the drift in Tcore and prevent or delay the expected decline in cognitive performance to exposure to cool on cognitive function will be investigated as well.
Primary Specific Aim: To determine the change in: (1) Tcore and (2) cognitive performance (attention, working memory, processing speed, and executive function) in persons with tetraplegia after exposure to a cool environment (64°F) for up to 120 min in the seated position.
Primary Hypotheses:(1) 66% of persons with tetraplegia will demonstrate a decline of 1.8°F in Tcore while 0% of controls will demonstrate that same thermal decline; (2) 80% of persons with tetraplegia will have a decline of at least 1 T-score in Stroop Interference scores (executive functioning) while 30% of controls will demonstrate that same magnitude of decline.
Secondary Specific Aims: To determine the change in: (1) the average of distal skin temperatures, (2) metabolic rate, and (3) subjective rating of thermal sensitivity after exposure to 64°F in the seated position.
Secondary Hypotheses: 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.
Tertiary Specific Aim: To determine if a single, 10 mg dose of midodrine will (1) reduce the decrease in Tcore and (2) prevent or delay the decline in cognitive performance in the group with tetraplegia.
Tertiary Hypotheses: Because administration of a peripheral alpha-agonist will address the primary thermoregulatory impairment to cool temperature exposure in persons with tetraplegia—that is, lack of vasoconstriction, the midodrine-induced peripheral vasoconstriction will be anticipated to blunt the decrease in Tcore and prevent or delay the decline in cognitive performance compared to cool exposure without drug administration.
Preparation for Study Visits: The study visits will be separated by a minimum of 1 day and no more than 14 days. Subjects will wear minimal clothing (gym shorts, sports bra) during the study to maximize bare skin exposure to the cool temperature. Each subject will be asked to eat a light, standard meal 2 hours prior to their scheduled visit consisting of either a plain bagel or 2 pieces of toast. For each visit they will be asked to empty their bladders prior to arrival and again upon arrival, if needed.
Visit 1: Cold Ambient Challenge: Instrumentation: During Visit 1, all subjects will be transferred to a padded table for instrumentation, after which they will be transferred back to their own wheelchair or, for controls, to a provided wheelchair. All subjects will use a Roho seat cushion for air circulation consistency and decubiti prevention. A rectal probe will be placed 4 inches beyond the anal sphincter for core temperature measurement, and skin thermal sensors will be taped at 15 sites above and below the level of lesion for collection of skin temperatures. A mask will be placed over the subject's nose and mouth for measurement of exhaled gases from which resting metabolic rate will be calculated from analysis of expired gases (VO2) by a metabolic cart. Laser Doppler flowmetry (LDF) will be used to measure changes in microvascular perfusion by taping a doppler probe on the skin in the area of the ulnar styloid processes and medial malleoli bilaterally (wrists and ankles) to confirm vasoconstriction. A pulse oximeter will be placed on the left second digit to obtain blood oxygen saturation and heart rate (HR). An automated blood pressure cuff will be placed above the right elbow to measure brachial BP. An intravenous catheter will be placed in the right antecubital or nearby vein and secured for sequential blood collection for cortisol and norepinephrine.
Baseline Collection: At the end of the 30 minute acclimation period (81°F), a baseline (BL) collection of the following parameters will be performed for 15 minutes with Tcore, skin temperatures, and VO2 measured continuously; HR, BP, blood oxygen saturation, subjective measures of thermal sensitivity, and 5 minutes of LDF will be measured at 10 minute intervals. A venous blood draw will be collected once at baseline for norepinephrine and cortisol concentrations. At the end of the BL period, a cognitive performance battery will be administered.
Thermal Challenge: Following completion of the baseline period, subjects will be wheeled into an 18°C thermal chamber for 120 minutes or until Tcore ≤ 95°F. Tcore, skin temperatures, and VO2 will be continuously monitored to ensure subject safety throughout the protocol; brachial BP, HR, blood oxygen saturation, thermal sensitivity, and symptoms of hypothermia and autonomic dysreflexia will be assessed at 10 min intervals while LDF will be measured for 5 minutes every 20 minutes. Venous blood will be collected at 50 minute intervals. A decrease in Tcore to ≤ 95°F, or moderate subject discomfort, will result in termination of the protocol. The cognitive performance battery will be administered when Tcore has declined 1.8°F or is ≤ 95.9°F (in subjects with tetraplegia) or after 120 minutes of cold exposure (in both groups) on Visits 1 & 2.
Visit 2: Cold Ambient Challenge with Midodrine: Visit 2 will be completed in subjects with tetraplegia who participated in Visit 1 and who had an impaired ability to maintain Tcore. Following completion of the BL period, subjects will be orally administered midodrine hydrochloride (10 mg tablet). Forty minutes after midodrine administration (for onset of drug effect), a second BL collection will be obtained, and subjects will be wheeled into the 64°F thermal chamber for 120 minutes or until Tcore ≤ 95°F. Data collection will follow the same schedule and be conducted in the seated position as in Visit 1. If brachial BP increases to 160/90 mmHg, the subject will be removed from the cool room and evaluated by Dr. William A. Bauman, who may consider the administration of labetalol (to lower BP), if deemed necessary.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
|Intervention ICMJE||Drug: Midodrine hydrochloride
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 effects of this drug improve the ability to maintain body core temperature 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)
|Publications *||Handrakis JP, Liu SA, Rosado-Rivera D, Krajewski M, Spungen AM, Bang C, Swonger K, Bauman WA. Effect of Mild Cold Exposure on Cognition in Persons with Tetraplegia. J Neurotrauma. 2015 Aug 1;32(15):1168-75. doi: 10.1089/neu.2014.3719. Epub 2015 Mar 31.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Actual Study Completion Date||October 2015|
|Actual Primary Completion Date||October 2015 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 68 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01822535|
|Other Study ID Numbers ICMJE||01374|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||John Handrakis, PT, DPT, EdD, James J. Peters Veterans Affairs Medical Center|
|Study Sponsor ICMJE||James J. Peters Veterans Affairs Medical Center|
|Collaborators ICMJE||Not Provided|
|PRS Account||James J. Peters Veterans Affairs Medical Center|
|Verification Date||February 2016|
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