Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02379156 |
| Other study ID # |
HAN-14-045 |
| Secondary ID |
31569601589 |
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
April 2015 |
| Est. completion date |
December 2021 |
Study information
| Verified date |
June 2021 |
| Source |
James J. Peters Veterans Affairs Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
This study will investigate the mechanisms contributing to thermoregulatory fragility in
persons with tetraplegia when exposed to cool ambient temperatures that are routinely
encountered during their activities of daily living (ADL). Subnormal body core temperatures
and vulnerability to hypothermia (Tcore<95°F) have 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 and to attain the maximal degree of independence possible. The one-time
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.
Preparation for Study Visits:
The study visits will be at least 1 day apart but no more than 2 weeks apart. Subjects will
be provided a light, standard meal which they will be asked to eat 2 hours prior to their
scheduled visit time. The meal will be either a plain bagel or 2 pieces of toast. For each
visit, subjects will be asked to empty their bladders before their arrival and again upon
arrival, if needed. Subjects will be asked to avoid caffeinated and alcoholic beverages and
heavy exertion for 24-hours before testing. Subjects will wear minimal clothing (gym shorts,
sports bra) during the study to maximize bare skin exposure to the cool temperature.
Visit 1: Cold Ambient Challenge Instrumentation: During the subject's first visit, a thin
flexible rectal sensor will be placed 4 inches beyond the anal sphincter for Tcore
measurement, and skin thermal sensors will be taped at 15 sites above and below the level of
lesion for collection of skin temperature (Tsk). 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 laser doppler
probe on the skin in the area of the ulnar styloid processes and medial malleoli bilaterally
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 blood pressure (BP). An intravenous catheter
will be placed in the right antecubital or nearby vein and secured for sequential blood
collection for blood hormones (cortisol and norepinephrine).
Baseline Collection: At the end of the 30-minute acclimation period (81°F), a 15-minute
baseline (BL) collection of the following measures will be performed: Tcore, Tsk, and VO2
will be measured continuously; BP, HR, blood oxygenation, and thermal sensitivity will be
measured at 5-minute intervals; 5 minutes of LDF will be measured at 10-minute intervals; a
venous blood draw will be collected once for norepinephrine and cortisol concentrations. At
the end of the BL period, a cognitive performance battery will be given.
Cool Ambient Challenge: Following the completion of the baseline period, subjects will be
wheeled into a 64°F thermal room for 120 minutes or until Tcore ≤ 95°F. Tcore, Tsk, and VO2
will be continuously monitored for safety throughout the study, while BP, HR, blood
oxygenation, and thermal sensitivity will be measured every 10 minutes. LDF will be measured
for 5 minutes every 25 minutes, and Venous blood will be collected every 60 minutes. 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).
A decrease in Tcore to ≤ 95°F, or moderate subject discomfort, will result in termination of
the protocol. Subjects will be transferred to a warm room (81°F), covered with warming
blankets, and given warm fluids. If symptoms continue, Dr. William Bauman will assess the
subject and provide the appropriate care.
Visit 2: Cold Ambient Challenge with Midodrine Visit 2 will be completed in the subjects with
tetraplegia who participated in Visit 1 and demonstrated an impaired ability to maintain
Tcore. All procedures will be conducted in the seated position and will be the same as in
Visit 1, with the exception of the oral administration of a 10 mg tablet of midodrine
hydrochloride following the completion of the baseline period. Forty minutes after midodrine
administration (in order for the medicine's effects to start), a second baseline collection
will be performed and subjects will then be placed inside the 64°F thermal room for up to 2
hours or until Tcore ≤ 95°F. Data collection will follow the same schedule and be conducted
in the same seated position as in Visit 1. During Visit 2, BP will be continuously monitored
after midodrine administration for safety purposes. If subjects' BP increases to 160/90 mmHg,
subjects will be seen by Dr. William Bauman, who may consider the administration of
labetalol, if necessary.
