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Identification of the Epigenetic Response to Trauma (TrauMeth)

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ClinicalTrials.gov Identifier: NCT03974048
Recruitment Status : Recruiting
First Posted : June 4, 2019
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Trine Grodum Eskesen, Rigshospitalet, Denmark

Brief Summary:
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.

Condition or disease Intervention/treatment
Trauma Injuries Diagnostic Test: Blood samples for DNA methylation analysis

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.


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Study Type : Observational
Estimated Enrollment : 360 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Identification of the Epigenetic Response to Trauma - a Prospective, Observational Study
Actual Study Start Date : June 3, 2019
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : October 1, 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Organ dysfunction [ Time Frame: Day 30 after trauma/surgery ]
    Occurrence of organ dysfunction (increase of ≥ 2 in SOFA-score)

  7. Sepsis/septic shock [ Time Frame: Day 30 after trauma/surgery ]
    Occurrence of sepsis or septic shock


Biospecimen Retention:   Samples With DNA
Blood samples are obtained from patients to investigate DNA methylation profiles


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03974048


Contacts
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Contact: Trine G Eskesen, MD 004535458211 trine.grodum.eskesen.01@regionh.dk
Contact: Jacob Steinmetz, MD, Ph.D. 004535458434 jacob.steinmetz@regionh.dk

Locations
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Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Trine G Eskesen, MD    004535458211    trine.grodum.eskesen.01@regionh.dk   
Contact: Jacob Steinmetz, MD, Ph.D.    004535458434    jacob.steinmetz@regionh.dk   
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
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Study Director: Jacob Steinmetz, MD, Ph.D. Rigshospitalet, Denmark

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Responsible Party: Trine Grodum Eskesen, Medical Doctor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT03974048     History of Changes
Other Study ID Numbers: VD-2019-161
First Posted: June 4, 2019    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Trine Grodum Eskesen, Rigshospitalet, Denmark:
Epigenetics
DNA methylation
Trauma

Additional relevant MeSH terms:
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Wounds and Injuries