Identification of the Epigenetic Response to Trauma (TrauMeth)

November 8, 2021 updated by: Trine Grodum Eskesen, Rigshospitalet, Denmark

Identification of the Epigenetic Response to Trauma - a Prospective, Observational Study

The objective of this study is to investigate potential early alterations in the DNA methylation profile after severe trauma and to investigate if the early marks persist.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background: Severe trauma is an extreme physical exposure, which may have significant consequences for the patient. In addition to anatomical injury and hemodynamic compromise, severe trauma causes an immense and rapid systemic immune reaction. At the genomic level, trauma has been found to significantly increase gene expression in circulating leukocytes, and preliminary data is also emerging that trauma may even cause epigenetic (DNA methylation) alterations.

Epigenetics, including DNA methylation, have been suggested as a mediator of genetic risk and to play a significant role in subsequent non-traumatic disease. Within the field of trauma DNA methylation has only been sparsely studied, but a few studies of traumatized animals have suggested that DNA methylation alterations may occur in relation to trauma. Even though DNA methylation is highly dynamic, some marks have been found to be stable over time, and thus may have long-term consequences.

An increasing understanding of the role of epigenetics in disease development and response may pave the way for new treatment targets and modalities for multiple diseases including trauma.

Research question: Does trauma induce immediate (<4 hours) and persistent (30 days post-trauma) changes in the epigenome of peripheral blood cells, and do epigenetic changes correlate with patient recovery?

Objectives: To identify potential early alterations in the DNA methylation profile after severe trauma AND to investigate if the early marks persist.

Study design: A prospective, observational, cohort study of trauma patients admitted to RH's trauma center. The trauma cohort will be compared to a cohort of patients admitted for elective orthopedic surgery in terms of DNA methylation profile in blood cells pre-trauma/surgery, immediately post-trauma/surgery, and 30-45 days post-trauma/surgery.

DNA methylation profiles will be assessed by array technique using Illumina's MethylationEPIC Bead-Chip.

Primary outcome: Immediate (<4 hours) post-trauma DNA methylation profile in blood cells.

Secondary outcomes: Pre-trauma/surgery DNA methylation profile, change in DNA methylation from pre-trauma/surgery to immediately and 30 days post-trauma/surgery, occurrence of organ dysfunction, sepsis, septic shock, 30-day mortality, ICU admission > 24 hours, ICU length of stay (LOS), hospital LOS.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
365

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study population consists of all trauma patients admitted to RH's trauma center generating a trauma team activation.

The control group will consist of patients admitted to RH's orthopedic department for elective surgery.

Description

Inclusion Criteria:

  • Age 18-65 years.
  • Trauma patients: Admitted to Rigshospitalet's trauma center generating a trauma team activation.

  • Surgical controls: Admitted for elective surgery (non-traumatic cause) at the orthopedics department AND

    • Only one surgical procedure planned from study day 0 to study day 45.
    • Expected procedure length of at least 60 minutes.

Exclusion Criteria:

  • Not able to obtain informed consent and not possible to obtain consent from a next-of-kin.

  • Trauma patients:

    • Secondary transfers.
    • Pre-hospital blood transfusion OR blood transfusion in the trauma center before the first blood sample is obtained.
    • First blood sample taken later than 4 hours after the trauma.
    • Patients in cardiac arrest before/after hospital admission.
    • Additional traumatic exposure requiring hospital admission between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).
    • Surgery not related to the trauma between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).

  • Surgical controls:

    • Surgical procedures due to cancer or fractures.
    • Traumatic exposure requiring hospital admission between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).
    • Additional, unplanned surgery between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).
    • First post-operative blood sample taken later than 4 hours after surgical end time.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Trauma patients
All trauma patients admitted to Rigshospitalet's trauma center will have a blood sample taken during the initial treatment and 30 days after the trauma.
Diagnostic test: Blood samples for DNA methylation analysis
DNA from blood samples will be isolated and analyzed for genome-wide DNA methylation patterns using the Infinium HumanMethylationEPIC BeadChip (Illumina, San Diego, CA, USA).
Patients admitted for elective orthopedic surgery
The patients will have a blood sample taken before and after surgery and again 30 days after the surgery.
Diagnostic test: Blood samples for DNA methylation analysis
DNA from blood samples will be isolated and analyzed for genome-wide DNA methylation patterns using the Infinium HumanMethylationEPIC BeadChip (Illumina, San Diego, CA, USA).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Immediate DNA methylation profile
Time Frame: Day of trauma/surgery
Immediate (< 4 hours) post-trauma DNA methylation profile in blood cells compared to the pre-surgery (baseline) and immediate post-surgery (< 4 hours) DNA methylation profile in blood cells.
Day of trauma/surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pre-trauma/-surgery DNA methylation profile
Time Frame: Pre-trauma/surgery
Pre-trauma (if possible to obtain from an existing biobank) DNA methylation profile in blood cells compared to pre-surgery.
Pre-trauma/surgery
Stability of DNA methylation profile
Time Frame: 30-45 days after trauma/surgery
Persistence of the DNA methylation profile in blood cells 30-45 days after the trauma compared to surgical patients.
30-45 days after trauma/surgery
Change in DNA methylation profile; pre-trauma/-surgery to post-trauma/-surgery
Time Frame: Day of trauma/surgery
Change in DNA methylation profile in blood cells from pre-trauma (if possible to obtain) to immediately post-trauma compared to surgical patients.
Day of trauma/surgery
Change in DNA methylation profile; immediately post-trauma/-surgery to one month post-trauma/-surgery
Time Frame: 0 to 30-45 days after trauma/surgery
Change in DNA methylation profile in blood cells from immediately post-trauma to 30-45 days post-trauma compared to surgical patients.
0 to 30-45 days after trauma/surgery
DNA methylation changes in relation to injury severity
Time Frame: Day 0-45 after trauma/surgery
Association of DNA methylation changes with injury severity. This will be done by comparing the DNA methylation profiles among patient with an injury severity score (ISS) < 15 and patients with an ISS > 15.
Day 0-45 after trauma/surgery
Organ dysfunction
Time Frame: Day 30 after trauma/surgery
Occurrence of organ dysfunction (increase of ≥ 2 in SOFA-score)
Day 30 after trauma/surgery
Sepsis/septic shock
Time Frame: Day 30 after trauma/surgery
Occurrence of sepsis or septic shock
Day 30 after trauma/surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Rigshospitalet, Denmark

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Jacob Steinmetz, MD, Ph.D., Rigshospitalet, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 3, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 15, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 29, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 3, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 4, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VD-2019-161

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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