Clinical trial NCT03899532: Remote Ischemic Conditioning in Traumatic Brain Injury
Official title: The Effect of Remote Ischemic Conditioning (RIC) on Inflammatory Biomarkers and Outcomes in Patients With TBI
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Traumatic Brain Injury
Brain Injuries
Brain Trauma
Brain Injuries, Traumatic
Keywords: Remote Ischemic Conditioning
Traumatic Brain Injury
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2019-04-02
Enrollment: 0
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in the level of Inflammatory Biomarkers (pg/ml)
timeFrame: 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
measure: Change in the level of C-reactive protein C-reactive Protein mg/dl
timeFrame: 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
measure: Change in the Level of pro-calcitonin (ng/ml)
timeFrame: 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
measure: Change in the Level of cardiac biomarker: Troponin c (ng/ml)
timeFrame: 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
measure: Change in the Level of cardiac biomarker: Creatinine Phosphokinase (ug/ml)
timeFrame: 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
measure: Change in the Level of cardiac biomarker: Creatine Kinase MB CKMB (ug/ml)
timeFrame: 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
Secondary outcomes:
measure: Discharge Disposition/Destination
timeFrame: Last hospitalization day
measure: Mortality
timeFrame: Last hospitalization day, 30 days post-discharge
measure: Glasgow Outcome Scale-Extended (points)
timeFrame: Last hospitalization day, 30 days
measure: Glasgow Coma Scale (points)
timeFrame: Last hospitalization day, 30 days
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner University Medical Center
state: Arizona
Study officials:
affiliation: University of Arizona
name: Bellal Joseph, MD
role: PRINCIPAL_INVESTIGATOR
References:
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