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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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The purpose of this project is to test how ketamine, an analgesics currently employed in the pre-hospital setting by the US Army, alters the capacity to tolerate a hemorrhagic insult in humans.
Pain management on the battlefield is critical for the wellbeing of the soldier. Given that a hemorrhagic injury on the battlefield is virtually always associated with pain, it is paramount that the selected pain medication does not disrupt appropriate physiological mechanisms that are beneficial towards the maintenance of blood pressure and vital organ blood flow during that hemorrhagic insult. Current guidelines for the selection of pain medications of a hemorrhaging soldier are based upon limited scientific evidence, with the vast majority of supporting studies being conducted on anesthetized animals. Thus, the interaction between hemorrhagic shock and pain medications commonly employed on the battlefield is yet to be determined in the conscious humans.
With this background, we will test the hypothesis that ketamine will impair the capacity for a conscious human to tolerate a hemorrhagic insult.
The obtained data will provide the necessary scientific evidence in humans to support the Committee on Tactical Combat Casualty Care (CoTCCC) guidelines on the analgesic of choice for moderate to severe injuries where the casualty is in hemorrhagic shock. Notably, such data will identify the analgesic that least compromises a human's ability to tolerate a hemorrhagic insult, ultimately providing critical information to the combat medic on which analgesic should be employed for such an injury.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine | Experimental | Subjects will receive up to 20 mg Ketamine Hydrochloride while the effects of this drug on tolerance to a hemorrhagic insult will be assessed. |
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| Placebo | Placebo Comparator | Subjects will receive placebo while the effects of this drug on tolerance to a hemorrhagic insult will be assessed. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine Hydrochloride | Drug | A total of 20 mg of Ketamine Hydrochloride will be administered intravenously |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Stress Index | Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and ketamine limbs, by causing progressive central hypovolemia via lower-body negative pressure (LBNP). This progressive lower-body negative pressure challenge will be performed until the onset of syncopal symptoms (defined as: profound bradycardia, a precipitous drop in arterial blood pressure and accompanying narrowing of pulse pressure, a sustained systolic blood pressure less than 80 mmHg, and/or subjective symptoms such as light-headedness, sweating, nausea, or dizziness). The primary variable will be the quantification of lower-body negative pressure that is required to cause these symptoms. This quantification will be objectively measured via a cumulative stress index which is calculated as the sum of the product of the LBNP level and the duration of each level, until test termination (i.e., 40 mmHg x 3 min + 50 mmHg x 3 min, etc). | 12 month |
| Measure | Description | Time Frame |
|---|---|---|
| Pressure Pain Tolerance | Pain assessments will be conducted using a digital algometer to obtain maximum pain thresholds caused by pressure. This pain assessment technique is conducted by applying the tip of a hand-held digital algometer on the subject's digit. Force is gradually increased and the peak force is recorded when the subject first reports a painful sensation. Removal of the pressure from the algometer immediately relieves the painful sensation and the subject can voluntarily stop the test at any time. This assessment will be performed after the subject has received placebo and ketamine. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| craig G Crandall, Ph.D. | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Texas Health Presbyterian Hospital Dallas | Dallas | Texas | 75231 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33017047 | Background | Watso JC, Huang M, Moralez G, Cramer MN, Hendrix JM, Cimino FA 3rd, Belval LN, Hinojosa-Laborde C, Crandall CG. Low dose ketamine reduces pain perception and blood pressure, but not muscle sympathetic nerve activity, responses during a cold pressor test. J Physiol. 2021 Jan;599(1):67-81. doi: 10.1113/JP280706. Epub 2020 Oct 20. | |
| 33084081 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine First, Then Placebo | Ketamine visit (20 mg) first, then Placebo visit (saline) |
| FG001 | Placebo First, Then Ketamine | Placebo visit (saline) first, then Ketamine visit (20 mg) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Enrollment |
| |||||||||||||
| First Visit |
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| Washout (at Least 48 Hours) |
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| Second Visit |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative Stress Index | Tolerance to a simulated hemorrhagic challenge will be assessed, for both the placebo and ketamine limbs, by causing progressive central hypovolemia via lower-body negative pressure (LBNP). This progressive lower-body negative pressure challenge will be performed until the onset of syncopal symptoms (defined as: profound bradycardia, a precipitous drop in arterial blood pressure and accompanying narrowing of pulse pressure, a sustained systolic blood pressure less than 80 mmHg, and/or subjective symptoms such as light-headedness, sweating, nausea, or dizziness). The primary variable will be the quantification of lower-body negative pressure that is required to cause these symptoms. This quantification will be objectively measured via a cumulative stress index which is calculated as the sum of the product of the LBNP level and the duration of each level, until test termination (i.e., 40 mmHg x 3 min + 50 mmHg x 3 min, etc). | Posted | Mean | Standard Deviation | mmHg x minutes | 12 month |
|
Adverse event data were collected from until discharge from the final data collection visit, which typically occurred 6 to 12 months after consent/screening.
Each participant completed both drug and placebo conditions, therefore, groups are combined for adverse event reporting.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ketamine | Ketamine trials | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Craig Crandall | University of Texas Southwestern Medical Center | 2143454623 | craigcrandall@texashealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 23, 2019 | Oct 27, 2021 | Prot_003.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2021 | Oct 15, 2021 | SAP_004.pdf |
| ICF | No | No | Yes | Informed Consent Form | Sep 23, 2019 | Oct 27, 2021 | ICF_005.pdf |
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| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo | Other | Subjects will receive placebo |
|
| 12 months |
| Huang M, Watso JC, Moralez G, Cramer MN, Hendrix JM, Yoo JK, Badrov MB, Fu Q, Hinojosa-Laborde C, Crandall CG. Low-dose ketamine affects blood pressure, but not muscle sympathetic nerve activity, during progressive central hypovolemia without altering tolerance. J Physiol. 2020 Dec;598(24):5661-5672. doi: 10.1113/JP280491. Epub 2020 Oct 20. |
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| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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Subjects will receive up to 20 mg Ketamine Hydrochloride while the effects of this drug on tolerance to a hemorrhagic insult will be assessed. Ketamine Hydrochloride: A total of 20 mg of Ketamine Hydrochloride will be administered intravenously |
| OG001 | Placebo | Subjects will receive placebo while the effects of this drug on tolerance to a hemorrhagic insult will be assessed. Placebo: Subjects will receive placebo |
|
|
| Secondary | Pressure Pain Tolerance | Pain assessments will be conducted using a digital algometer to obtain maximum pain thresholds caused by pressure. This pain assessment technique is conducted by applying the tip of a hand-held digital algometer on the subject's digit. Force is gradually increased and the peak force is recorded when the subject first reports a painful sensation. Removal of the pressure from the algometer immediately relieves the painful sensation and the subject can voluntarily stop the test at any time. This assessment will be performed after the subject has received placebo and ketamine. | Pressure pain tolerance was evaluated in a subset of individuals | Posted | Mean | Standard Deviation | Kilograms | 12 months |
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| 30 |
| 0 |
| 30 |
| 0 |
| 30 |
| EG001 | Placebo | Placebo trials | 0 | 30 | 0 | 30 | 0 | 30 |
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| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |