Effect of Severe Trauma on PD1 and Its Legend (PD1/L1) on T Lymphocytes and Correlation With Mortality

Trauma Patients Clinical Trial

Official title:

Effect of Severe Trauma on Programmed Death Molecule (PD1) and Its Legend (PD1/L1) on T Lymphocytes and Correlation With Mortality

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04233723
• Other study ID #: IRB171000017
• Status: Not yet recruiting
• Start date: April 1, 2020
• Est. completion date: February 1, 2021

Study information

• Verified date: February 2019
• Source: Assiut University
• Contact: Ramy R Hennis, MD
• Phone: 01094703771
• Email: ramtragaie80[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Unlike neuro-endocrine response to trauma; posttraumatic immune alterations are not easily carried out at bedside. The majority of trials were conducted in the intensive care usually hours to days post injury.

In this trial the investigators sought assess the immune responses during emergency department trauma resuscitation by looking at the biomarkers of severe injury by comparing T lymphocytes and programmed cell death molecules and its relation with mortality.

Description:

Trauma is a major healthcare problem with a high mortality rate that might be caused by immune-suppression.

Trauma initiates an immunosuppressive response which is contributor tocell damage and could be a marker of multi organ failure and mortality.

Programmed cell death receptor-1 (PD-1) and programmed cell death receptor ligand-1 (PD-L1), which are co-inhibitory receptor molecules, may participate in trauma-induced immune-suppression.

Both sterile and infected trauma induce the systemic inflammatory response syndrome (SIRS), originally defined by pyrexia, tachycardia, hyperventilation and neutrophilia, the latter responding poorly to pathogens. (10) Accompanying these changes is a decrease in circulating basophil, eosinophil and natural killer precursors, which further weakens systemic immunity.

Apoptosis (Programmed Cell Death):

Programmed cell-death (PCD) is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. Apoptosis and autophagy are both forms of PCD, but necrosis is a non-physiological process that occurs as a result of infection or injury.

Programmed cell death protein 1 Programmed cell death protein 1, also known as PD-1 and CD 279 (cluster of differentiation 279), is a protein that in humans is encoded by the PDCD1 gene. PD-1 is a cell surface receptor that belongs to the immunoglobulin super family and is expressed on T cells and pro-B cells. PD-1 binds two ligands, PD-L1 and PD-L2. PD-1, functioning as an immune checkpoint, plays an important role in down regulating the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance.

Ligands PD-1 has two ligands, PD-L1 and PD-L2, which are members of the B7 family. Several lines of evidence suggest that PD-1 and its ligands negatively regulate immune responses PD-1 knockout mice have been shown to develop lupus-like glomerulo-nephritis and dilated cardiomyopathy Triggering PD-1, expressed on monocytes and up-regulated upon monocytes activation, by its ligand PD-L1 induces IL-10 production which inhibits CD4 T-cell function.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: February 1, 2021
• Est. primary completion date: January 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult trauma patients with blunt or penetrating injury.

2. Major injury:

• Injury severity score > 15

• Drop in hematocrit > 10 points

• Transfusion of more than 6-10 units of packed RBCs

• Serum lactate > 3 mmol/L

3. Mean arterial blood pressure = 60 mmHg and/or systolic arterial blood pressure = 90 mmHg.

4. Patients admitted to the ED within 6 hours after the onset of trauma

Exclusion Criteria:

• 1. age less than 18 years; 2. patients who died within 2 days of the onset of trauma; 3. patients who declined to consent; 4. Known pregnancy. 5. Patients with limb ischemia or peripheral vascular occlusion. 6. Patients admitted to the emergency trauma department after 6 hours of the trauma event.

7. Preexisting conditions as severe cardiovascular disease, uncontrolled hemorrhage.

Related Conditions & MeSH terms

• Trauma Patients
• Wounds and Injuries

Intervention

Other:
• peripheral blood samples
venous puncture

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (4)

Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R. Bacterial programmed cell death and multicellular behavior in bacteria. PLoS Genet. 2006 Oct;2(10):e135. Review. — View Citation

Islam N, Whitehouse M, Mehendale S, Hall M, Tierney J, O'Connell E, Blom A, Bannister G, Hinde J, Ceredig R, Bradley BA. Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty. Clin Exp Immunol. 2014 Aug;177(2):509-20. doi: 10.1111/cei.12351. — View Citation

Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity. 2013 Feb 21;38(2):209-23. doi: 10.1016/j.immuni.2013.02.003. Review. — View Citation

Murray CK, Hinkle MK, Yun HC. History of infections associated with combat-related injuries. J Trauma. 2008 Mar;64(3 Suppl):S221-31. doi: 10.1097/TA.0b013e318163c40b. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measuring standard deviations of biomarkers of severe injury by comparing T lymphocytes and programmed cell death molecules and its relation with mortality.	Results for normally distributed continuous variables will be expressed as mean value, standard deviation and inter-quartile range. Categorical data and dichotomous variables will be shown as number and percentage.; Comparisons of continuous variables will be performed using independent t-test. Proportions will be compared with chi-square test.	48 hours