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Remote Ischemic Conditioning in Traumatic Brain Injury (MOTION)

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ClinicalTrials.gov Identifier: NCT03899532
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
University of Arizona

Brief Summary:

Traumatic brain injury (TBI) is a leading cause of death among trauma patients accounting for one-third of all trauma mortalities. Patients who survive the initial trauma are liable to secondary insults from the ensuing inflammatory state in the brain. Treatment goals are aimed at reducing secondary injury. Maintaining adequate brain perfusion, limiting cerebral edema, and optimizing oxygen delivery are part of established treatment protocols. Numerous therapeutics have been evaluated as potential treatment for TBI with very limited success and there is no medication that alters survival.

Various novel therapeutic options have been investigated to prevent the secondary brain injury. Remote Ischemic Conditioning (RIC) is one of these therapies. RIC involves decreasing blood flow to a normal tissue usually the arm by inflating the blood pressure cuff 30mmHg over the systolic blood pressure. The decreased blood flow or ischemia is maintained for 5 minutes followed by releasing the pressure and re-perfusion of the arm. This cycle is usually repeated 4 times. RIC has been shown to improve outcomes in patients with heart attacks, strokes, elective neurosurgeries.

A prospective observational study and a randomized clinical trial has shown the protective effect of RIC in TBI patients. Additionally, multiple studies in animals have shown that RIC is neuroprotective after TBI. RIC is non-invasive and harmless except for a little discomfort in the arm. The aim of the study is to evaluate the impact of RIC on long term outcomes in patients with TBI.


Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Brain Injuries Brain Trauma Brain Injuries, Traumatic Device: Remote Ischemic Conditioning Other: No-Remote Ischemic Conditioning Not Applicable

Detailed Description:

Traumatic brain injury (TBI) remains one of the leading causes of death and disability in the United States. Secondary brain injury caused by the complex interplay of inflammatory mediators induced by a primary insult is the major contributing factor for morbidity and mortality after TBI. While the primary injury is irreversible, the inflammatory cascade leading to the development of the secondary injury may be preventable. As a result, all the current research in TBI is focused on preventing initiation of this secondary insult.

Remote ischemic conditioning (RIC) is a process where normal tissues are subjected to short cycles of ischemia and reperfusion, which have been shown to reduce the sequelae of an ischemic injury at a remotely injured site. RIC has been shown to improve the outcomes after myocardial infarction, sepsis, transplantation, reimplantation, and elective neurologic surgery.It is thought to work by releasing endogenous systemic anti-inflammatory mediators and humoral factors and by using neural pathways, rendering global protection to the body against subsequent ischemic insults in a remote are. This protection provided by RIC has two phases, an early (short) phase and a late (prolonged) phase, both of which have proven to be effective in reducing ischemic size and improving survival. Multiple animal studies and a small randomized clinical trial have shown the protective effect of RIC in patients with TBI. The effectiveness of RIC in patients with traumatic brain injury is still under investigation not yet established.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Remote Ischemic Conditioning (RIC) on Inflammatory Biomarkers and Outcomes in Patients With TBI
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : May 30, 2021
Estimated Study Completion Date : May 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Remote Ischemic Conditioning

Remote ischemic conditioning will be performed using a standard manual blood pressure cuff. The pressure in the blood pressure cuff will be maintained at 30 mm of Hg higher than the patient's systolic blood pressure. 4 cycles of ischemic conditioning will be performed each day for a period of 7 days. Each cycle consists of 5 min of controlled upper limb ischemia (cuff up) followed by 5 min of reperfusion (cuff down). The total duration of the treatment cycle will be 40 min. The study protocol is based on our published literature in traumatic brain injury.

Blood samples will be collected at 0 hours (before randomization). Then the first 4 cycles of RIC (done consecutively) will be performed, blood samples will be taken at 6 hours post randomization and then at 24 hours post randomization. RIC cycles will then be performed on a daily basis followed by taking a blood sample once daily during the patients' length of stay up to a maximum of 7 days

Device: Remote Ischemic Conditioning
Standard manual blood pressure cuff

Placebo Comparator: No Remote Ischemic Conditioning
Blood samples will be collected at 0 hours (before randomization). Blood samples will then be collected at 6 hours post randomization and 24 hours post randomization. These patients will not receive daily RIC therapy but will only have their blood drawn once daily during the patients' length of stay up to a maximum of 7 days.
Other: No-Remote Ischemic Conditioning
No-Remote Ischemic Conditioning




Primary Outcome Measures :
  1. Change in the level of Inflammatory Biomarkers (pg/ml) [ Time Frame: Before randomization, 6 hours post randomization, 24 hours post randomization, once daily during the patients' length of stay up to a maximum of 7 days afterwards ]
    Level of tumor necrosis factor alpha (TNF-alpha), Level of interleukin 1 (IL-1),Level of interleukin 6 (IL-6), Level of interleukin 8 (IL-8), and Level of interleukin 10 (IL-10).

  2. Change in the level of C-reactive protein C-RP mg/dl [ Time Frame: Before randomization, 6 hours post randomization, 24 hours post randomization, once daily during the patients' length of stay up to a maximum of 7 days afterwards ]
    C-reactive protein

  3. Change in the Level of pro-calcitonin (ng/ml) [ Time Frame: Before randomization, 6 hours post randomization, 24 hours post randomization, once daily during the patients' length of stay up to a maximum of 7 days afterwards ]
    Level of pro-calcitonin

  4. Change in the Level of cardiac biomarker: Troponin c (ng/ml) [ Time Frame: Before randomization, 6 hours post randomization, 24 hours post randomization, once daily during the patients' length of stay up to a maximum of 7 days afterwards ]
    Troponin c

  5. Change in the Level of cardiac biomarker: CPK Creatinine Phosphokinase (ug/ml) [ Time Frame: Before randomization, 6 hours post randomization, 24 hours post randomization, once daily during the patients' length of stay up to a maximum of 7 days afterwards ]
    Creatinine Phosphokinase

  6. Change in the Level of cardiac biomarker: Creatine Kinase MB CKMB (ug/ml) [ Time Frame: Before randomization, 6 hours post randomization, 24 hours post randomization, once daily during the patients' length of stay up to a maximum of 7 days afterwards ]
    Creatine Kinase MB


Secondary Outcome Measures :
  1. Discharge Disposition/Destination [ Time Frame: Last hospitalization day ]
  2. Mortality [ Time Frame: Last hospitalization day, 30 days post-discharge ]
  3. Glasgow Outcome Scale-Extended (points) [ Time Frame: Last hospitilzation day, 30 days ]
    Functional independence level assessment: The Extended Glasgow Outcome Scale (GOSE) is a global scale for functional outcome that rates patients into eight categories. The categories of severe disability, moderate disability and good recovery are subdivided into a lower and upper category. The scale will be used to evaluate the patient's functional status

  4. Glasgow Coma Scale (points) [ Time Frame: Last hospitalization day, 30 days ]

    Neurological status assessment The Glasgow Coma Scale is divided into three components which are scored separately: ocular response (assessment 1-4 points), motor response (assessment 1-6 points) verbal response (evaluation of 1-5 points).

    Scores for each component are added together to get the total that will range between a minimum of 3 points (which corresponds to a patient who does not open his eyes and no motor response to stimulation or verbal response) and a maximum value of 15 points (corresponding to a patient with open eyes, obeying orders and maintaining a consistent language).

    It has been considered that the GCS score between 15 and 13 points corresponds to a slight alteration of consciousness, a score of 12-9 points with moderate impairment and 8 points or less with a serious deterioration in level of consciousness.




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Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 17years.
  2. Diagnosis of traumatic brain injury.
  3. Glasgow Coma Scale (GCS) ≤13
  4. Intra-cranial hemorrhage (ICH) on initial brain CT scan

Exclusion Criteria:

  1. Patients with traumatic brain injury >24 hours
  2. Transferred from other centers
  3. Declined to participate in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03899532


Contacts
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Contact: Bellal Joseph, MD (520) 626-5056 bjoseph@surgery.arizona.edu
Contact: Kamil Hanna, MD (520) 626-5056 kamilhanna@surgery.arizona.edu

Locations
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United States, Arizona
Banner University Medical Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Kamil Hanna, MD    520-369-0706    kamilhanna@surgery.arizona.edu   
Sponsors and Collaborators
University of Arizona
Investigators
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Principal Investigator: Bellal Joseph, MD University of Arizona

Publications:
CDCVTBI in the US ReportVTraumatic Brain Injury. Injury Center 2014. Available at: http://www.cdc.gov/traumaticbraininjury/tbi_ed.html#3. Accessed July 22, 2014

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Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT03899532     History of Changes
Other Study ID Numbers: 1901298756
First Posted: April 2, 2019    Key Record Dates
Last Update Posted: April 2, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by University of Arizona:
Remote Ischemic Conditioning
Traumatic Brain Injury

Additional relevant MeSH terms:
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Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System