Investigating gut microbiome changes in sepsis and trauma survivors

Microbiome Dysfunction in Surgical Intensive Care Unit Survivors Subtitle: The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma Pathological Myeloid Activation After Sepsis and Trauma

This study is trying to see how changes in gut bacteria affect recovery in people who survived sepsis or severe trauma, including those with traumatic brain injuries.

Quick facts

• Study type: Observational
• Enrollment: 468 (estimated)
• Ages: 18 Years to 110 Years
• Sex: All
• Sponsor: University of Florida (Academic / other)
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT05357170 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the relationship between gut microbiome dysfunction and persistent systemic inflammation in survivors of sepsis and severe trauma. Researchers will collect stool and blood samples from 216 participants, including 108 sepsis survivors and 108 trauma survivors, across different age groups. The samples will undergo 16S rRNA DNA sequencing to analyze microbiota alterations over time and compare these findings with a healthy control group. Additionally, a subgroup of trauma patients with traumatic brain injury will be included to assess the impact of inflammation on recovery outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older who have been diagnosed with sepsis and have remained in the ICU for at least 14 days.

Not a fit: Patients with severe traumatic brain injury or those expected to die within 12 hours are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of long-term complications in sepsis and trauma survivors.

How similar studies have performed: While the specific focus on gut microbiome in sepsis and trauma survivors is relatively novel, related studies have shown promising results in understanding microbiome impacts on health.

Eligibility criteria

Sepsis Population

Inclusion Criteria

1. Admission to the 46, 77, 87, 4 East, 4 West, or 24-5 ICUs where clinical care can be managed by the critical care organization guided by standard operating procedures.
2. Age ≥18 years
3. Meets Sepsis 3 criteria at time of sepsis diagnosis
4. Has remained in ICU for 14 days (+/- 7 days) following sepsis diagnosis.
5. Ability to obtain patient/LAR informed consent.
6. Is receiving adequate nutritional intake: oral or enteral nutrition.

Exclusion Criteria

1. Severe traumatic brain injury with unencumbered assessment of GCS equaling 3 on admission to intensive care unit
2. Refractory shock (i.e., patients who are expected to die within 12 hours).
3. Uncontrollable source of sepsis (e.g. irreversible disease state such as unresectable dead bowel).
4. Patient or patient's family are not committed to aggressive management of the patient's condition.
5. Known HIV infection with CD4 count \<200 cells/mm3.
6. Organ transplant recipient on immunosuppressive agents.
7. Known pregnancy.
8. Prisoners.
9. Institutionalized patients j Inability to obtain informed consent.

k) Burn injury greater than 20% TBSA (total body surface area)

Trauma Population

Inclusion Criteria

1\. All adults (age ≥18 to 54) require both:

a. Blunt and/or penetrating trauma patient with i. Hemorrhagic shock defined by:

1\. Systolic BP (SBP) ≤ 90 mmHg or 2. Mean arterial pressure ≤ 65 mmHg or 3. Base deficit (BD) ≥5 meq or 4. Lactate ≥ 2 or 5. Active red blood cell or whole blood transfusion within 6 hours of arrival

b. Injury Severity Score (ISS) greater than or equal to 15

2\. All adults (age 55 and older) require:

a. Either hemorrhagic shock defined by: i. Systolic BP (SBP) ≤ 90 mmHg or ii. Mean arterial pressure ≤ 65 mmHg or iii. Base deficit (BD) ≥5 meq or iv. Lactate ≥ 2 or v. Active red blood cell or whole blood transfusion within 6 hours of arrival

OR

b. Injury Severity Score (ISS) greater than or equal to 15. 3. Ability to obtain Informed Consent

Exclusion Criteria

1. Patients not expected to survive greater than 48 hours.
2. Prisoners.
3. Pregnancy.
4. Previous bone marrow transplantation.
5. Patients with End Stage Renal Disease.
6. Patients with any pre-existing hematological disease (e.g. hemochromatosis, myelodysplastic syndrome, hematologic cancers)
7. Burn injury greater than 20% TBSA
8. Severe traumatic brain injury with unencumbered assessment of GCS equaling 3 on admission to intensive care unit.

Trauma TBI subgroup (15 participants)

Inclusion criteria will be:

1\. Any adult age 18 or older with any traumatic bleed (intracerebral hemorrhage, subarachnoid hemorrhage, intraparenchymal hemorrhage, subdural hematoma, cerebral epidural hematoma) and any GCS (Glasgow Coma Score).

Exclusion criteria is the same used for the trauma cohort.

Cardiac-Surgery operation:

Inclusion Criteria:

1. Adult (\>18 years age) patients undergoing open cardiac surgery
2. Ability to obtain patient informed consent
3. was placed on cardiopulmonary bypass at their initial operation at UF Health

Exclusion Criteria:

1. Inability to obtain informed consent,
2. Pregnancy
3. Evidence of multi-organ failure on presentation
4. Patients with any pre-existing hematological disease (e.g. hemochromatosis, myelodysplastic syndrome, hematologic cancers
5. Prisoners
6. Previous bone marrow transplantation
7. Burn injury greater than 20% TBSA

Open abdominal vascular operation:

Inclusion Criteria:

1. Adult (\>18 years age) patients undergoing open abdominal vascular surgery
2. Ability to obtain patient informed consent,

Exclusion Criteria:

1. Inability to obtain informed consent,
2. Pregnancy
3. Evidence of multi-organ failure on presentation
4. Patients with any pre-existing hematological disease (e.g. hemochromatosis, myelodysplastic syndrome, hematologic cancers
5. Prisoners
6. Previous bone marrow transplantation.
7. Burn injury greater than 20% TBSA

Healthy Control

Inclusion criteria will be:

1. All adults (age ≥18)
2. Ability to obtain Informed Consent prior to blood collection.

Exclusion Criteria will be:

1. Current, chronic steroid use
2. Pregnancy
3. Current or recent (within 7 days) use of antibiotics.

Where this trial is running

Gainesville, Florida

• UF Health at Shands Hospital — Gainesville, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Philip Efron, MD — UF COM Department of Surgery
• Study coordinator: Ruth Davis, BSN

Conditions Sepsis, Trauma Injury; Sepsis; Trauma; Microbiome