HMGB1 Release From Hemorrhagic Shock Patients
Evidence for SIRT1 Mediated HMGB1 Release From Kidney Cells in the Early Stages of Hemorrhagic Shock
1 other identifier
observational
18
1 country
1
Brief Summary
It is reported that high mobility group box 1 (HMGB1), a non-histone nuclear protein, can serve as an alarmin with damage associated molecular patterns to activate immune responses in the early stages of hemorrhagic shock (HS). However, the origin of HMGB1 and how it is released following HS is poorly understood. In this study, we teased out this mechanism. We try to record the concentration of serum HMGB1 protein following HS in clinical patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started May 2017
Shorter than P25 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 17, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 11, 2018
CompletedFirst Submitted
Initial submission to the registry
May 11, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 11, 2018
CompletedFirst Posted
Study publicly available on registry
May 24, 2018
CompletedMay 24, 2018
May 1, 2018
11 months
May 11, 2018
May 14, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
serum HMGB1 concentration
the concentration of serum HMGB1 were progressively increased following Hemorrhagic shock
24 hours following hemorrhagic shock
Study Arms (2)
voluteer group
No treatment, only blood sample collection
hemorrhagic shock group
HS was defined as out-of-hospital systolic blood pressure (SBP) of 70 mmHg or less or SBP ranging 71 to 90 mmHg with a heart rate of 108 beats/min or more. Exclusion criteria were pregnancy, \<15 years old, more than 2,000 mL of intravenous fluids or blood before enrollment, hypothermia, drowning, asphyxia, burns, isolated penetrating head injury, time of call received by dispatch to study intervention longer than 4 h, known prisoners, and transfer from another hospital
Eligibility Criteria
Healthy volunteers OR Hemorrhagic shock (HS) patients enrolled in ICU
You may qualify if:
- Hemorrhagic shock (HS) was defined as out-of-hospital systolic blood pressure (SBP) of 70 mmHg or less or SBP ranging 71 to 90 mmHg with a heart rate of 108 beats/min or more.
You may not qualify if:
- pregnancy, \<18 years old, more than 2,000 mL of intravenous fluids or blood before enrollment, hypothermia, drowning, asphyxia, burns, isolated penetrating head injury, time of call received by dispatch to study intervention longer than 4 h, known prisoners, and transfer from another hospital
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Xingui Dailead
Study Sites (1)
The First Hospital of Chenzhou
Chenzhou, Hunan, 450003, China
Related Publications (4)
Rickenbacher A, Jang JH, Limani P, Ungethum U, Lehmann K, Oberkofler CE, Weber A, Graf R, Humar B, Clavien PA. Fasting protects liver from ischemic injury through Sirt1-mediated downregulation of circulating HMGB1 in mice. J Hepatol. 2014 Aug;61(2):301-8. doi: 10.1016/j.jhep.2014.04.010. Epub 2014 Apr 18.
PMID: 24751831RESULTRabadi MM, Xavier S, Vasko R, Kaur K, Goligorksy MS, Ratliff BB. High-mobility group box 1 is a novel deacetylation target of Sirtuin1. Kidney Int. 2015 Jan;87(1):95-108. doi: 10.1038/ki.2014.217. Epub 2014 Jun 18.
PMID: 24940804RESULTHwang JS, Lee WJ, Kang ES, Ham SA, Yoo T, Paek KS, Lim DS, Do JT, Seo HG. Ligand-activated peroxisome proliferator-activated receptor-delta and -gamma inhibit lipopolysaccharide-primed release of high mobility group box 1 through upregulation of SIRT1. Cell Death Dis. 2014 Oct 2;5(10):e1432. doi: 10.1038/cddis.2014.406.
PMID: 25275593RESULTHwang JS, Choi HS, Ham SA, Yoo T, Lee WJ, Paek KS, Seo HG. Deacetylation-mediated interaction of SIRT1-HMGB1 improves survival in a mouse model of endotoxemia. Sci Rep. 2015 Nov 2;5:15971. doi: 10.1038/srep15971.
PMID: 26522327RESULT
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- serum HHMGB1 concentration of hemorrhagic shock patients
Study Record Dates
First Submitted
May 11, 2018
First Posted
May 24, 2018
Study Start
May 17, 2017
Primary Completion
April 11, 2018
Study Completion
May 11, 2018
Last Updated
May 24, 2018
Record last verified: 2018-05
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- 72 hours following hemorrhagic shock
- Access Criteria
- HS was defined as out-of-hospital systolic blood pressure (SBP) of 70 mmHg or less or SBP ranging 71 to 90 mmHg with a heart rate of 108 beats/min or more. Exclusion criteria were pregnancy, \<18 years old, more than 2,000 mL of intravenous fluids or blood before enrollment, hypothermia, drowning, asphyxia, burns, isolated penetrating head injury, time of call received by dispatch to study intervention longer than 4 h, known prisoners, and transfer from another hospital
Hemorrhagic shock (HS) is a pathologic process caused by insufficient perfusion in multiple organs, and usually initiates a systemic post-traumatic inflammation response. The resulting increased inflammation response may accelerate the multiple organ dysfunctions . Extracellular high-mobility group box 1 (HMGB1) was found to mediate inflammation during sterile and infectious injury and contributes significantly to disease pathogenesis. However, the exact role of HMGB1-mediated inflammation in HS is not fully understood. In this study, we first test the serum HMGB1 concentration in clinical HS patients and then we explored the underlying mechanism in HS animal model. An unexpected mechanism of HMGB1 released from multiple organs (especially in kidney) was found.