Remote Ischemic Conditioning in Traumatic Brain Injury

NCT03899532 | Withdrawn FDA Device

• 1 other identifier: 1901298756
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury; Brain Injuries; Brain Trauma; Brain Injuries, Traumatic

Keywords

Remote Ischemic Conditioning; Traumatic Brain Injury

Outcome Measures

Primary Outcomes (6)

• 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).

  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

• Change in the level of C-reactive protein C-reactive Protein mg/dl

  C-reactive protein

  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

• Change in the Level of pro-calcitonin (ng/ml)

  Level of pro-calcitonin

  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

• Change in the Level of cardiac biomarker: Troponin c (ng/ml)

  Troponin c

  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

• Change in the Level of cardiac biomarker: Creatinine Phosphokinase (ug/ml)

  Creatinine Phosphokinase

  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

• Change in the Level of cardiac biomarker: Creatine Kinase MB CKMB (ug/ml)

  Creatine Kinase MB

  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 (4)

• Discharge Disposition/Destination

  Last hospitalization day

• Mortality

  Last hospitalization day, 30 days post-discharge

• Glasgow Outcome Scale-Extended (points)

  Last hospitalization day, 30 days

• Glasgow Coma Scale (points)

  Last hospitalization day, 30 days

Study Arms (2)

Remote Ischemic Conditioning

EXPERIMENTAL

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

No Remote Ischemic Conditioning

PLACEBO COMPARATOR

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

Interventions

Remote Ischemic Conditioning DEVICE

Standard manual blood pressure cuff

Remote Ischemic Conditioning

No-Remote Ischemic Conditioning OTHER

No-Remote Ischemic Conditioning

No Remote Ischemic Conditioning

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients with traumatic brain injury \>24 hours
• Transferred from other centers
• Declined to participate in the study

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

Banner University Medical Center

Tucson, Arizona, 85724, United States

Location

Related Publications (15)

• 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

  BACKGROUND

• Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007 Jul;99(1):4-9. doi: 10.1093/bja/aem131.

  PMID: 17573392 BACKGROUND

• Stein DM, Kufera JA, Lindell A, Murdock KR, Menaker J, Bochicchio GV, Aarabi B, Scalea TM. Association of CSF biomarkers and secondary insults following severe traumatic brain injury. Neurocrit Care. 2011 Apr;14(2):200-7. doi: 10.1007/s12028-010-9496-1.

  PMID: 21210304 BACKGROUND

• Saxena P, Newman MA, Shehatha JS, Redington AN, Konstantinov IE. Remote ischemic conditioning: evolution of the concept, mechanisms, and clinical application. J Card Surg. 2010 Jan-Feb;25(1):127-34. doi: 10.1111/j.1540-8191.2009.00820.x. Epub 2009 Jun 22.

  PMID: 19549044 BACKGROUND

• Munk K, Andersen NH, Schmidt MR, Nielsen SS, Terkelsen CJ, Sloth E, Botker HE, Nielsen TT, Poulsen SH. Remote Ischemic Conditioning in Patients With Myocardial Infarction Treated With Primary Angioplasty: Impact on Left Ventricular Function Assessed by Comprehensive Echocardiography and Gated Single-Photon Emission CT. Circ Cardiovasc Imaging. 2010 Nov;3(6):656-62. doi: 10.1161/CIRCIMAGING.110.957340. Epub 2010 Sep 8.

  PMID: 20826592 BACKGROUND

• Lim SY, Hausenloy DJ. Remote ischemic conditioning: from bench to bedside. Front Physiol. 2012 Feb 20;3:27. doi: 10.3389/fphys.2012.00027. eCollection 2012.

  PMID: 22363297 BACKGROUND

• Konstantinov IE, Arab S, Kharbanda RK, Li J, Cheung MM, Cherepanov V, Downey GP, Liu PP, Cukerman E, Coles JG, Redington AN. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. 2004 Sep 16;19(1):143-50. doi: 10.1152/physiolgenomics.00046.2004. Epub 2004 Aug 10.

  PMID: 15304621 BACKGROUND

• Steiger HJ, Hanggi D. Ischaemic preconditioning of the brain, mechanisms and applications. Acta Neurochir (Wien). 2007 Jan;149(1):1-10. doi: 10.1007/s00701-006-1057-1. Epub 2006 Dec 14.

  PMID: 17151832 BACKGROUND

• Konstantinov IE, Li J, Cheung MM, Shimizu M, Stokoe J, Kharbanda RK, Redington AN. Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism. Transplantation. 2005 Jun 27;79(12):1691-5. doi: 10.1097/01.tp.0000159137.76400.5d.

  PMID: 15973170 BACKGROUND

• Hu S, Dong HL, Li YZ, Luo ZJ, Sun L, Yang QZ, Yang LF, Xiong L. Effects of remote ischemic preconditioning on biochemical markers and neurologic outcomes in patients undergoing elective cervical decompression surgery: a prospective randomized controlled trial. J Neurosurg Anesthesiol. 2010 Jan;22(1):46-52. doi: 10.1097/ANA.0b013e3181c572bd.

  PMID: 19996767 BACKGROUND

• Sahebally SM, Healy D, Coffey JC, Walsh SR. Should patients taking aspirin for secondary prevention continue or discontinue the medication prior to elective, abdominal surgery? Best evidence topic (BET). Int J Surg. 2014;12(5):16-21. doi: 10.1016/j.ijsu.2013.11.004. Epub 2013 Nov 15.

  PMID: 24246172 BACKGROUND

• Loukogeorgakis SP, Williams R, Panagiotidou AT, Kolvekar SK, Donald A, Cole TJ, Yellon DM, Deanfield JE, MacAllister RJ. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation. 2007 Sep 18;116(12):1386-95. doi: 10.1161/CIRCULATIONAHA.106.653782. Epub 2007 Aug 27.

  PMID: 17724264 BACKGROUND

• Wei M, Xin P, Li S, Tao J, Li Y, Li J, Liu M, Li J, Zhu W, Redington AN. Repeated remote ischemic postconditioning protects against adverse left ventricular remodeling and improves survival in a rat model of myocardial infarction. Circ Res. 2011 May 13;108(10):1220-5. doi: 10.1161/CIRCRESAHA.110.236190. Epub 2011 Apr 7.

  PMID: 21474817 BACKGROUND

• Andreka G, Vertesaljai M, Szantho G, Font G, Piroth Z, Fontos G, Juhasz ED, Szekely L, Szelid Z, Turner MS, Ashrafian H, Frenneaux MP, Andreka P. Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs. Heart. 2007 Jun;93(6):749-52. doi: 10.1136/hrt.2006.114504. Epub 2007 Apr 20.

  PMID: 17449499 BACKGROUND

• Loukogeorgakis SP, Panagiotidou AT, Broadhead MW, Donald A, Deanfield JE, MacAllister RJ. Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system. J Am Coll Cardiol. 2005 Aug 2;46(3):450-6. doi: 10.1016/j.jacc.2005.04.044.

  PMID: 16053957 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Injuries

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Bellal Joseph, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 2, 2019
• Study Start: September 24, 2019
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: April 4, 2025

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)