Trauma PatientsNCT04233723
Effect of Severe Trauma on PD1 and Its Legend (PD1/L1) on T Lymphocytes and Correlation With Mortality
An observational study of Trauma Patients, run by Assiut University.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Trauma Patients
- What is being tested?
- peripheral blood samples
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2020to 1 Feb 2021
- How long will I take part?
- 2 Days
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: trauma emergency department and Trauma ICU of Assiut university hospital.
Who may be able to join
- Adult trauma patients with blunt or penetrating injury.
- 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
- Mean arterial blood pressure ≤ 60 mmHg and/or systolic arterial blood pressure ≤ 90 mmHg.
- Patients admitted to the ED within 6 hours after the onset of trauma
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effect of Severe Trauma on Programmed Death Molecule (PD1) and Its Legend (PD1/L1) on T Lymphocytes and Correlation With Mortality
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.
Read the detailed 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.
- Conditions
- Trauma Patients
- Being tested
- peripheral blood samples
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
peripheral blood samplesOther
venous puncture
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start1 Apr 2020 (estimated)
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Feb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Trauma PatientsStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 2 Days
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, RRHennis, Assiut University
- Investigators
- Ramy R Hennis, Principal investigator, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04233723
- Sponsor's protocol ID
- IRB171000017
- Status last verified
- Feb 2019
- First submitted
- 15 Mar 2019
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. doi: 10.1371/journal.pgen.0020135.
PubMed 17069462Islam 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.
PubMed 24749651Murray 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.
PubMed 18316966Kaczmarek 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.
PubMed 23438821
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Severe Trauma on Programmed Death Molecule (PD1) and Its Legend (PD1/L1) on T Lymphocytes and Correlation With Mortality
- ClinicalTrials.gov ID
- NCT04233723
- Acronym / sponsor ID
- IRB171000017
- Conditions
- Trauma Patients
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Apr 2020 (estimated)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Feb 2021 (estimated)
- First posted
- 18 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Target follow-up
- 2 Days
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- trauma emergency department and Trauma ICU of Assiut university hospital.
Key inclusion criteria (8 listed)
- Adult trauma patients with blunt or penetrating injury.
- Major injury:
- Mean arterial blood pressure ≤ 60 mmHg and/or systolic arterial blood pressure ≤ 90 mmHg.
- Patients admitted to the ED within 6 hours after the onset of trauma
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| peripheral blood samplesvenous puncture | Other | – |
Primary outcome
Measuring standard deviations of biomarkers of severe injury by comparing T lymphocytes and programmed cell death molecules and its relation with mortality.
Time frame: 48 hours
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Background: PubMed 17069462Engelberg-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. doi: 10.1371/journal.pgen.0020135.
- Background: PubMed 24749651Islam 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.
- Background: PubMed 18316966Murray 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.
- Background: PubMed 23438821Kaczmarek 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramy R Hennis principal investigator
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of Trauma Patients, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ramy R Hennis, MD (01094703771, ramtragaie80@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measuring standard deviations of biomarkers of severe injury by comparing T lymphocytes and programmed cell death molecules and its relation with mortality. (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04233723, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.