DengueDEN-SEPNCT07040202
Immune Responses to Dengue and Sepsis
An observational study of Dengue and Sepsis, run by Institut Pasteur du Cambodge at 4 sites in Cambodia.
Trial summary
The goal of this research study is to help the investigators better understand serious dengue disease. The investigators will collect clinical information and up to four blood samples from participants with dengue, influenza, sepsis, or healthy people. Read more about this study
- Who is it for?
- Ages 2 years and olderHealthy volunteers can take part
- Type of treatment
- Pill or oral medicine
- How many people
- 240 participants
- Where
- 4 sitesCambodia
- Study dates
- 2 Jun 2025to Jul 2027
- How long will I take part?
- 21 Days
- Phase
- Observational
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 2 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients will be enrolled from Kampong Speu District Referral Hospital (Kampong Speu), Preah Kossamak Hospital (Phnom Penh), National Pediatric Hospital (Phnom Penh), and the International Center of Excellence in Research Cambodia.
Who may be able to join
- Patients with dengue-like illness:
- Patients presenting with dengue-like symptoms for a duration of maximum 72h before inclusion. Dengue-like symptoms include: presentation with oral temperature >38°C AND at least two of the following symptoms suggestive of dengue-like illness: headache, retro-orbital pain, myalgia, joint pain, rash, any bleeding symptoms, nausea or vomiting, lethargy or restlessness , abdominal pain, liver enlargement
- Influenza patients: Patients presenting with with oral temperature >38°C and cough that started within the last 4 days AND rapid test or PCR positive for influenza infection AND no COVID-19 or positive bacterial cultures at the time of enrollment.
- Sepsis patients:
- Patients admitted for less than 48 hours with a primary diagnosis of sepsis as per treating team AND have blood cultures ordered AND on empiric antibiotics due to concern for bacterial infection.
- Healthy controls:
- Participants with no chronic illness, no regular medications, no febrile illness in 28 days, no diagnosis of or treatment for dengue or bacterial infection in the past 6 months.
Who cannot join
- For biobanking purposes, children less than 2 years of age, and individuals who are pregnant, pregnant within the last 90 days, and/or breastfeeding are excluded due to restrictions on the blood volumes and the repeated sampling times.
- Individuals that do not provide informed consent will not be included for the study.
- Severe/chronic/recurrent pathological conditions: clinically significant autoimmune disease or immunodeficiency (including history of organ transplant), haematologic disorders, cardiac diseases, diabetes, cancer, HIV, chronic hepatic or renal insufficiency.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to the inclusion. For corticosteroids, this will mean a dose equivalent to 20 mg/day of prednisone or equivalent for > 2 weeks (inhaled and topical steroids allowed)
- Chronic administration of NSAIDs, including aspirin: prolonged intake (>2 weeks) within 6 months before study or any intake within the 7 days preceding sampling [exception for low dose aspirin: maximum 250mg/daily]
- Any underlying, chronic, or current condition that, in the opinion of the investigator, may interfere with their participation in the study.
- Expected death in the next 48-hours
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Camila D Odio, MD contact
Cambodia4 sites, 4 recruiting
- Recruiting
Kampong Speu District Referral Hospital
Kampong Speu
Chanthap Lon, MD, 855 12976 799, lonc@icercambodia.org
- Recruiting
International Center of Excellence in Research Cambodia
Phnom Penh
Chanthap Lon, MD, 85512976799, lonc@icercambodia.org
- Recruiting
National Pediatric Hospital
Phnom Penh
Chanthap Lon, MD, +855 12976 799, lonc@icercambodia.org
- Recruiting
Preah Kossamak Hospital
Phnom Penh
Chanthap Lon, MD, 85512976799, lonc@icercambodia.org
About this study
Official title: Evaluating Immune Responses to Dengue and Sepsis in Hospitalized Patients in Cambodia
The goal of this research study is to help the investigators better understand serious dengue disease. The investigators will collect clinical information and up to four blood samples from participants with dengue, influenza, sepsis, or healthy people. The investigators will perform multiple analyses on the blood samples and compare results between dengue patients and those with influenza or sepsis and healthy people.
Read the detailed description
This is an observational study enrolling n=200 hospitalized individuals with dengue-like illness, n=50 individuals with influenza, n=30 individuals with sepsis, and n<=50 healthy controls to evaluate immune responses in syndromes that cause plasma leak and organ damage. Sepsis and dengue patients will have blood collected at enrollment, day 1, and day 3, and dengue patients will have an additional blood draw at day 21. Influenza patients will have a nasopharyngeal swab and blood collected at enrollment, and blood collected at days 3 and 21. Healthy participants will have a single blood draw at enrollment. The blood collected will enable the evaluation of immune kinetics, including changes in neutrophils, cytokines, and adaptive responses, as dengue progresses or improves. Overall, this study will facilitate the evaluation of an understudied cell type and will provide unique data for understanding the temporal changes in the immune response to dengue virus. A better understanding of dengue pathophysiology will help identify potential therapeutic targets to improve outcomes in this disease.
- Keywords
- dengue, sepsis, observational, infection, influenza
- Medical subject headings
- Dengue, Sepsis, Influenza, Human, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Participants with no chronic illness, no regular medications, no febrile illness in 28 days, no diagnosis of or treatment for dengue or bacterial infection in the past 6 months. | |
| Patients with dengue-like illness | Patients presenting with dengue-like symptoms for a duration of maximum 72h before inclusion. Dengue-like symptoms include: presentation with oral temperature >38°C AND at least two of the following symptoms suggestive of dengue-like illness: headache, retro-orbital pain, myalgia, joint pain, rash, any bleeding symptoms, nausea or vomiting, lethargy or restlessness, abdominal pain, liver enlargement. | |
| Sepsis patients | Patients admitted for less than 48 hours with a primary diagnosis of sepsis as per treating team AND have blood cultures ordered AND on empiric antibiotics due to concern for bacterial infection. | |
| Influenza patients | Patients with with oral temperature >38°C and cough that started within the last 4 days AND rapid test or PCR positive for influenza infection AND no COVID-19 or positive bacterial cultures at the time of enrollment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of low density neutrophils in mild/moderate vs severe dengue
Low density neutrophils will be isolated from the PBMC layer of centrifuged blood and characterized via flow cytometry. The percentages of low density neutrophils will be compared between dengue groups.
Measured: From enrollment to study day 3
Mean florescence intensity of neutrophils expressing spleen tyrosine kinase
The mean florescence intensity (MFI) of neutrophils expressing spleen tyrosine kinase will be measured via flow cytometry and compared between mild/moderate vs severe dengue.
Measured: From enrollment to study day 3.
Serum level of myeloperoxidase in mild/moderate versus severe dengue.
The serum level of myeloperoxidase will be measured in pg/mL and compared between participants with mild/moderate versus severe dengue.
Measured: Enrollment to study day 3
Secondary outcomes (9)
Percentage of low density neutrophils in dengue versus sepsis versus influenza.
Low density neutrophils will be isolated from the PBMC layer of centrifuged blood and characterized via flow cytometry. The percentage of low density neutrophils will be compared in dengue versus sepsis versus influenza.
Measured: From enrollment to study day 3
Mean florescence intensity of neutrophils expressing spleen tyrosine kinase in dengue versus sepsis versus influenza.
Mean florescence intensity (MFI) of neutrophils expressing spleen tyrosine kinase will be measured via flow cytometry and compared between those with dengue versus sepsis versus influenza. Other markers of neutrophil maturation, activation, and degranulation will be measured by flow cytometry and compared among dengue groups and between dengue and sepsis and influenza.
Measured: From enrollment to study day 3.
Serum level of myeloperoxidase in dengue versus sepsis versus influenza
Serum level of myeloperoxidase will be measured in pg/mL and compared between participants with dengue versus sepsis versus influenza. Other biomarkers of neutrophil activation such as calprotectin, resistin, and lactoferrin will be measured and compared among groups.
Measured: Enrollment to study day 3
Serum levels of interferon-gamma and interleukin-10 (pg/mL)
Serum levels of interferon-gamma and interleukin-10 (pg/mL) will be measured and compared between dengue groups, influenza, and sepsis overtime. Other cytokines may also be measured and compared among groups.
Measured: Enrollment through day 3.
Percentage of DENV-specific activated T cells
Activation induced marker assays will be used to compare dengue virus (DENV)-specific T cell activation over time in mild/moderate versus severe dengue.
Measured: Enrollment through day 21.
DENV1-4 geometric mean titer (GMT)
DENV1-4 GMT overtime will be compared between mild/moderate and severe dengue groups. These will also be correlated with disease outcome and GMT at convalescence.
Measured: Enrollment to day 21
Peak dengue virus enhancing titer
Peak dengue virus enhancing titer overtime will be compared between mild/moderate and severe dengue groups. These will also be correlated with disease outcome and GMT at convalescence.
Measured: Enrollment to day 21
Mean fluorescence intensity of specific lymphocyte populations among groups
Mean fluorescence intensity of specific lymphocyte populations will be compared mild/moderate versus severe dengue and dengue versus sepsis.
Measured: Enrollment to day 3
Number of differentially expressed genes among groups
The number of differentially expressed genes will be compared between mild/moderate and severe dengue and dengue versus sepsis versus influenza based on thresholds for statistical significance (e.g., adjusted p-value < 0.05) and magnitude of change (e.g., absolute log2 fold change > 1).
Measured: Enrollment to day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2025
- Study start2 Jun 2025
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DengueStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 240 participants (estimated)
- Target duration
- 21 Days
Sponsor and investigators
- Lead sponsor
- Institut Pasteur du Cambodge
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tineke Cantaert, PhD, Principal investigator, Institut Pasteur du Cambodge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07040202
- Sponsor's protocol ID
- 092 NECHR
- Other IDs
- Approval number
- Acronym
- DEN-SEP
- Status last verified
- Jul 2026
- First submitted
- 25 May 2025
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No