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Remote Ischemic Conditioning in Traumatic Brain Injury (MOTION)

Primary Purpose

Traumatic Brain Injury, Brain Injuries, Brain Trauma

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Remote Ischemic Conditioning
No-Remote Ischemic Conditioning
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Remote Ischemic Conditioning, Traumatic Brain Injury

Eligibility Criteria

17 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Banner University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Remote Ischemic Conditioning

No Remote Ischemic Conditioning

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Change in the level of Inflammatory Biomarkers (pg/ml)
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).
Change in the level of C-reactive protein C-reactive Protein mg/dl
C-reactive protein
Change in the Level of pro-calcitonin (ng/ml)
Level of pro-calcitonin
Change in the Level of cardiac biomarker: Troponin c (ng/ml)
Troponin c
Change in the Level of cardiac biomarker: Creatinine Phosphokinase (ug/ml)
Creatinine Phosphokinase
Change in the Level of cardiac biomarker: Creatine Kinase MB CKMB (ug/ml)
Creatine Kinase MB

Secondary Outcome Measures

Discharge Disposition/Destination
Mortality
Glasgow Outcome Scale-Extended (points)
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
Glasgow Coma Scale (points)
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.

Full Information

First Posted
March 27, 2019
Last Updated
May 23, 2022
Sponsor
University of Arizona
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1. Study Identification

Unique Protocol Identification Number
NCT03899532
Brief Title
Remote Ischemic Conditioning in Traumatic Brain Injury
Acronym
MOTION
Official Title
The Effect of Remote Ischemic Conditioning (RIC) on Inflammatory Biomarkers and Outcomes in Patients With TBI
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 24, 2019 (Actual)
Primary Completion Date
May 30, 2023 (Anticipated)
Study Completion Date
May 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury, Brain Injuries, Brain Trauma, Brain Injuries, Traumatic
Keywords
Remote Ischemic Conditioning, Traumatic Brain Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Remote Ischemic Conditioning
Arm Type
Experimental
Arm Description
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
Arm Title
No Remote Ischemic Conditioning
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Remote Ischemic Conditioning
Intervention Description
Standard manual blood pressure cuff
Intervention Type
Other
Intervention Name(s)
No-Remote Ischemic Conditioning
Intervention Description
No-Remote Ischemic Conditioning
Primary Outcome Measure Information:
Title
Change in the level of Inflammatory Biomarkers (pg/ml)
Description
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).
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
Title
Change in the level of C-reactive protein C-reactive Protein mg/dl
Description
C-reactive protein
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
Title
Change in the Level of pro-calcitonin (ng/ml)
Description
Level of pro-calcitonin
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
Title
Change in the Level of cardiac biomarker: Troponin c (ng/ml)
Description
Troponin c
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
Title
Change in the Level of cardiac biomarker: Creatinine Phosphokinase (ug/ml)
Description
Creatinine Phosphokinase
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
Title
Change in the Level of cardiac biomarker: Creatine Kinase MB CKMB (ug/ml)
Description
Creatine Kinase MB
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
Secondary Outcome Measure Information:
Title
Discharge Disposition/Destination
Time Frame
Last hospitalization day
Title
Mortality
Time Frame
Last hospitalization day, 30 days post-discharge
Title
Glasgow Outcome Scale-Extended (points)
Description
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
Time Frame
Last hospitalization day, 30 days
Title
Glasgow Coma Scale (points)
Description
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.
Time Frame
Last hospitalization day, 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 17years. Diagnosis of traumatic brain injury. Glasgow Coma Scale (GCS) ≤13 Intra-cranial hemorrhage (ICH) on initial brain CT scan Exclusion Criteria: Patients with traumatic brain injury >24 hours Transferred from other centers Declined to participate in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bellal Joseph, MD
Phone
(520) 626-5056
Email
bjoseph@surgery.arizona.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tawab Saljuqi, MD
Email
tsaljuqi@surgery.arizona.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bellal Joseph, MD
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner University Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tawab Saljuqi, MD
Phone
520-275-5306
Email
tsaljuqi@surgery.arizona.edu
First Name & Middle Initial & Last Name & Degree
Hamidreza Hosseinpour, MD
Email
Hosseinpourh@arizona.edu
First Name & Middle Initial & Last Name & Degree
Bellal Joseph, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
Citation
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Results Reference
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Remote Ischemic Conditioning in Traumatic Brain Injury

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