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SepsisNCT07680816

Metabolic and Functional Study of γδ T Cells in Critically Ill Patients

An observational study of Sepsis and Critical Illness, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This prospective observational cohort study investigates the subset-specific metabolic adaptation and functional remodeling of cytotoxic γδ T cells in critically ill patients with and without sepsis. Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Sepsis, Critical Illness, Immunosuppression
How many people
105 participants
Where
1 siteChina
Study dates
21 Jun 2026to 15 Jul 2027
Phase
Observational
Are there results?
Not yet: the study is under way

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 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: The study population comprises three distinct groups: healthy volunteers, non-septic critically ill patients, and septic critically ill patients admitted to the intensive care unit. Sepsis is defined according to the Sepsis-3 criteria (infection with an acute increase in SOFA score ≥2 points), while critical illness is based on standard ICU admission criteria. All participants must be aged ≥18 years and provide written informed consent (from the participant or a legally authorized representative for those unable to consent). Key exclusion criteria include known immunodeficiency, recent use of T-cell-targeted immunosuppressants or immune checkpoint inhibitors, expected ICU stay <24 hours, pregnancy, active major bleeding, or inability to obtain consent. Consecutive enrollment will take place at the Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, with follow-up through 90 days after enrollment.

Who may be able to join

  • Healthy Control Group (NHC):
  • Age ≥ 18 years.
  • No acute or chronic major diseases.
  • Provide written informed consent.
  • Non-septic Critical Illness Group (CI-NS):
  • Age ≥ 18 years.
Show all 13Show fewer
  • Admitted to the ICU and meeting the definition of critical illness.
  • Excluded from sepsis according to the Sepsis-3 criteria (infection + ΔSOFA ≥ 2 points).
  • Written informed consent provided by the participant or legally authorized representative.
  • Septic Critical Illness Group (CI-Sep):
  • Age ≥ 18 years.
  • Admitted to the ICU and meeting the Sepsis-3 criteria (infection + ΔSOFA ≥ 2 points).
  • Written informed consent provided by the participant or legally authorized representative.

Who cannot join

  • Age < 18 years.
  • Known immunodeficiency, HIV infection, active hematologic malignancy, or history of hematopoietic stem cell or solid organ transplantation within the past 3 months.
  • Receipt of T-cell-targeted immunosuppressive therapy (e.g., antithymocyte globulin, calcineurin inhibitors, mycophenolate mofetil, methotrexate, or high-dose corticosteroids >1 mg/kg/day prednisone equivalent) before ICU admission or within 24 hours after ICU admission.
  • Use of immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1/CTLA-4 antibodies) within the past 6 weeks.
  • Expected ICU stay < 24 hours or imminent risk of death (moribund state).
  • Pregnancy or breastfeeding.
  • Active major bleeding.
  • Inability to obtain informed consent.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site, 1 recruiting
  • Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

    Wuhan, Outside of the US, 430022

    Jiancheng Zhang, Dr., 13554105815, zhjcheng1@126.com

    Recruiting

Other trials in China

About this study

Official title: Subset-specific Metabolic Adaptation and Functional Remodeling of Gamma Delta T (γδ T) Cells in Critically Ill ICU Patients: A Single-center, Prospective, Observational Cohort Study.

This prospective observational cohort study investigates the subset-specific metabolic adaptation and functional remodeling of cytotoxic γδ T cells in critically ill patients with and without sepsis. As a bridge between innate and adaptive immunity, γδ T cells contribute to early antimicrobial defense; however, their cytotoxic function and its metabolic regulation in sepsis remain incompletely understood. Our preliminary single-cell transcriptomic analysis revealed altered expression of cytotoxicity-associated genes (GZMB, PRF1, and GNLY) and mitochondrial oxidative phosphorylation (OXPHOS) pathway genes in cytotoxic γδ T cells from patients with sepsis. In particular, COX6C expression correlated with cytotoxic effector gene expression. Across healthy volunteers, critically ill non-septic patients, and critically ill septic patients, we will integrate flow cytometry, mitochondrial function assays, and functional validation experiments to characterize circulating cytotoxic γδ T-cell abundance and function and examine the contribution of COX6C to mitochondrial dysfunction and impaired cytotoxicity.

To investigate the relationship between systemic tryptophan metabolism and these cellular abnormalities, targeted tryptophan-pathway metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) will quantify kynurenic acid (KYNA), tryptophan, kynurenine, and related metabolites in paired peripheral blood and fecal samples. Patients with sepsis will be stratified into older (≥65 years) and non-older (<65 years) groups and compared with age-matched healthy volunteers, with critically ill non-septic patients providing an additional disease control group. Metabolite concentrations and pathway-related ratios will be analyzed in relation to cytotoxic γδ T-cell abundance, cytotoxic function, mitochondrial OXPHOS, and COX6C expression, accounting for renal function, disease severity, antibiotic exposure, and nutritional support. These analyses will assess whether age-associated alterations in tryptophan metabolism, particularly KYNA, are associated with cytotoxic γδ T-cell dysfunction and identify candidate metabolic mechanisms for subsequent validation.

Medical subject headings
Sepsis, Critical Illness, Multiple Organ Failure, Mitochondrial Diseases, Dysbiosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07680816
Study groupRoleWhat they receive
Healthy Controls (NHCs)Healthy volunteers without acute or chronic major diseases, aged ≥18 years, who have provided written informed consent. Participants undergo a single blood draw and rectal swab collection.
Critically Ill Non-Septic Patients (CI-NS)Patients admitted to the ICU meeting the criteria for critical illness but without sepsis, as determined by the Sepsis-3 criteria (infection with ΔSOFA ≥ 2 points excluded). Participants are aged ≥18 years, with informed consent obtained from the patient or legally authorized representative. Blood and rectal swab samples are collected at three time points: within 24 hours of ICU admission (D0), Day 2 (D2), and Day 7 (D7). Clinical follow-up extends to 90 days.
Critically Ill Septic Patients (CI-Sep)Patients admitted to the ICU meeting the Sepsis-3 criteria (infection with ΔSOFA ≥ 2 points). Participants are aged ≥18 years, with informed consent obtained from the patient or legally authorized representative. Blood and rectal swab samples are collected at three time points: within 24 hours of ICU admission (D0), Day 2 (D2), and Day 7 (D7). Clinical follow-up extends to 90 days.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in the Proportion of Cytotoxic γδT Cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) Among Total γδT Cells

    Flow cytometric quantification of the frequency of Cytotoxic γδT cells, defined as TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺ cells, as a percentage of total γδT cells (TCRγδ⁺) in peripheral blood. This subset represents the cytotoxic effector population critical for early anti-infection defense.

    Measured: Within day 2 post-ICU admission

Secondary outcomes (26)
  1. Change in COX6C Expression in Cytotoxic γδT Cells

    Measurement of COX6C (mitochondrial respiratory chain complex IV subunit) expression levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at the mRNA level (by single-cell RNA sequencing) and protein level (by flow cytometry).

    Measured: Within day 2 post-ICU admission

  2. Blood Kynurenic Acid Level

    Peripheral blood KYNA concentration will be quantified using targeted tryptophan-pathway metabolomics by LC-MS/MS and compared among older patients with sepsis (≥65 years), non-older adult patients with sepsis (<65 years), and healthy volunteers.

    Measured: Within day 2 post-ICU admission

  3. Fecal Kynurenic Acid Level

    Fecal KYNA concentration will be quantified using targeted tryptophan-pathway metabolomics by LC-MS/MS and compared among older patients with sepsis (≥65 years), non-older adult patients with sepsis (<65 years), and healthy volunteers.

    Measured: Within day 2 post-ICU admission

  4. Blood Kynurenic Acid Levels and Their Associations With Cytotoxic γδ T-Cell Function

    Associations between peripheral blood KYNA concentrations, quantified by targeted LC-MS/MS, and prespecified quantitative measures of cytotoxic γδ T-cell function will be assessed in older patients with sepsis (≥65 years), non-older adult patients with sepsis (<65 years), and healthy volunteers.

    Measured: Within day 2 post-ICU admission

  5. Fecal Kynurenic Acid Levels and Their Associations With Cytotoxic γδ T-Cell Function

    Associations between fecal KYNA concentrations, quantified by targeted LC-MS/MS, and prespecified quantitative measures of circulating cytotoxic γδ T-cell function will be assessed in older patients with sepsis (≥65 years), non-older adult patients with sepsis (<65 years), and healthy volunteers.

    Measured: Within day 2 post-ICU admission

  6. Change in Cytotoxic Molecule Expression in Cytotoxic γδT Cells

    Flow cytometric quantification of the mean fluorescence intensity (MFI) of cytotoxic effector molecules including Granzyme B (GZMB), Perforin (PRF1), and Granulysin (GNLY) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).

    Measured: Within day 2 post-ICU admission

  7. Change in Mitochondrial Mass in Cytotoxic γδT Cell

    Flow cytometric quantification of mitochondrial mass using MitoTracker Green FM staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).

    Measured: Within day 2 post-ICU admission

  8. Change in Mitochondrial Membrane Potential (TMRE) in Cytotoxic γδT Cells

    Flow cytometric quantification of mitochondrial membrane potential using tetramethylrhodamine ethyl ester (TMRE) staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).

    Measured: Within day 2 post-ICU admission

  9. Change in Mitochondrial Membrane Potential (JC-1) in Cytotoxic γδT Cells

    Flow cytometric quantification of mitochondrial membrane potential using JC-1 dye (red/green fluorescence ratio) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).

    Measured: Within day 2 post-ICU admission

  10. Change in Oxygen Consumption Rate (OCR) in Cytotoxic γδT Cells

    Measurement of basal oxygen consumption rate reflecting oxidative phosphorylation (OXPHOS) capacity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).

    Measured: Within day 2 post-ICU admission

  11. Change in Extracellular Acidification Rate (ECAR) in Cytotoxic γδT Cells

    Measurement of basal extracellular acidification rate reflecting glycolytic metabolic activity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺).

    Measured: Within day 2 post-ICU admission

  12. Change in Glycolytic Capacity of Cytotoxic γδT Cells at Serial Time Points

    Longitudinal flow cytometric puromycin-incorporation assay (SCENITH method) to measure glycolytic capacity in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at Day 0, Day 2, and Day 7 post-ICU admission, to track the temporal evolution of metabolic flexibility and stress-adaptive glycolytic reprogramming during the course of critical illness.

    Measured: Day 0, Day 2, and Day 7 post-ICU admission

  13. Change in Mitochondrial ROS Levels in Cytotoxic γδT Cells at Serial Time Points

    Longitudinal flow cytometric quantification of mitochondrial reactive oxygen species (mitochondrial ROS) levels using MitoSOX Green staining in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at Day 0, Day 2, and Day 7 post-ICU admission, reflecting oxidative stress dynamics.

    Measured: Day 0, Day 2, and Day 7 post-ICU admission

  14. Change in Cytotoxic γδT Cell Migratory Function

    Assessment of Cytotoxic γδT cell (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) chemotactic and migratory capacity using Transwell migration assay.

    Measured: Within day 2 post-ICU admission

  15. Change in Total γδT Cell Proportion at Serial Time Points

    Longitudinal flow cytometric quantification of the frequency of total γδT cells (TCRγδ⁺) as a percentage of total live CD3⁺ T cells in peripheral blood at Day 0, Day 2, and Day 7 post-ICU admission.

    Measured: Day 0, Day 2, and Day 7 post-ICU admission

  16. Change in Cytotoxic γδT Cell Proportion at Serial Time Points

    Longitudinal flow cytometric quantification of the frequency of Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) as a percentage of total γδT cells at Day 0, Day 2, and Day 7 post-ICU admission, to track the temporal evolution of this cell subset.

    Measured: Day 0, Day 2, and Day 7 post-ICU admission

  17. Change in COX6C Expression in Cytotoxic γδT Cells at Serial Time Points

    Longitudinal measurement of COX6C expression levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) at Day 0, Day 2, and Day 7 post-ICU admission, to assess the temporal dynamics of mitochondrial metabolic gene expression.

    Measured: Day 0, Day 2, and Day 7 post-ICU admission

  18. Correlation Between Cytotoxic γδT Cell Glycolytic Capacity and APACHE II Score

    Spearman rank correlation analysis between glycolytic capacity (measured by puromycin incorporation assay at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with APACHE II (Acute Physiology and Chronic Health Evaluation II) score measured within the first 48 hours of ICU admission.

    Measured: Within day 2 post-ICU admission

  19. Correlation Between Cytotoxic γδT Cell Glycolytic Capacity and SOFA Score

    Spearman rank correlation analysis between glycolytic capacity (measured by puromycin incorporation assay at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with SOFA (Sequential Organ Failure Assessment) score measured within the first 48 hours of ICU admission.

    Measured: Within day 2 post-ICU admission

  20. Correlation Between Cytotoxic γδT Cell Metabolic Parameters and vasopressor dose

    Correlation analysis between COX6C expression, glycolytic capacity, and mitochondrial ROS levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with vasopressor dose (reported as norepinephrine equivalent dose, NEE).

    Measured: Within day 2 post-ICU admission

  21. Correlation Between Cytotoxic γδT Cell Metabolic Parameters and plasma lactate levels

    Correlation analysis between COX6C expression, glycolytic capacity, and mitochondrial ROS levels in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) with plasma lactate levels.

    Measured: Within day 2 post-ICU admission

  22. Association Between Cytotoxic γδT Cell Glycolytic Capacity and 28-day all-cause mortality

    Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and 28-day all-cause mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.

    Measured: Up to 90 days post-discharge

  23. Association Between Cytotoxic γδT Cell Glycolytic Capacity and 90-day all-cause mortality

    Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and 90-day all-cause mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.

    Measured: Up to 90 days post-discharge

  24. Association Between Cytotoxic γδT Cell Glycolytic Capacity and in-hospital mortality

    Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and in-hospital mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.

    Measured: Up to 90 days post-discharge

  25. Association Between Cytotoxic γδT Cell Glycolytic Capacity and ICU mortality

    Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and ICU mortality. Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.

    Measured: Up to 90 days post-discharge

  26. Association Between Cytotoxic γδT Cell Glycolytic Capacity and hospital length of stay

    Analysis of association between glycolytic capacity (measured at Day 2) in Cytotoxic γδT cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) and hospital length of stay (days). Patients will be stratified by vital status (survivors vs. non-survivors) and by hospital length of stay (above vs. below median) for comparative analysis.

    Measured: Up to 90 days post-discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2026
  2. Study start21 Jun 2026
  3. Primary completion15 Apr 2027 (estimated)
  4. Study completion15 Jul 2027 (estimated)

Resources

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
Cohort
Time perspective
Prospective
Enrolment
105 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07680816
Sponsor's protocol ID
zjc202612
Status last verified
Oct 2026
First submitted
25 Jun 2026
Last updated
27 Oct 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

An observational study of Sepsis and Critical Illness, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.

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 13 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the Proportion of Cytotoxic γδT Cells (TCRγδ⁺GZMB⁺PRF1⁺GNLY⁺) Among Total γδT Cells (time frame: Within day 2 post-ICU admission). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Oct 2026.

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