DENV Without Warning SignsCOMBATNCT06751836
Innovative Multidisciplinary Strategies for Combating Severe Dengue
An observational study of DENV Without Warning Signs and DENV with Warning Signs, run by Karolinska Institutet at 2 sites in 2 countries.
Trial summary
The goal of this observational study is to identify biomarkers and host factors associated with dengue severity in patients from dengue-endemic regions. The main question it aims to answer is: Can multi-omics approaches predict disease severity and identify key factors contributing to severe dengue infections?… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- DENV Without Warning Signs, DENV with Warning Signs, Severe Dengue
- What is being tested?
- Infection and no infection
- How many people
- 1,400 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 3 Jan 2025to 31 Oct 2029
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: * Patients who are pregnant, immunocompromised, or undergoing chemotherapy, on steroids or immunosuppressive drugs in the last year, liver cirrhosis, or coinfection with a non-dengue pathogen. * Cases with a lab-confirmed dengue infection within the past three months will excluded from the case cohort.
Who may be able to join
- Group 1: Dengue without warning signs Patients presenting with the following symptoms confirmed positive for dengue infection by lab diagnosis by anti-dengue IgM or NS1 ELISA will be recruited for the study under this cohort.
- Symptoms will be fever along with at least two of the following -
- Myalgia, arthralgia
- Nausea and/or vomiting
- Rashes
- Leukopenia Group 2: DENV with warning signs This cohort will include patients with the above symptoms and any of the following clinical signs.
Show all 19Show fewer
- Abdominal pain with tenderness
- Persistent vomiting
- Fluid accumulation
- Mucosal bleeding
- Restlessness, lethargy
- Liver enlargement >2cm
- Laboratory findings: An increase in hematocrit levels and a rapid decrease in platelet count Group 3: Severe dengue
- Severe plasma leakage leads to hypovolemic shock (dengue shock syndrome) and fluid accumulation with respiratory distress.
- Severe bleeding, such as epistaxis, internal bleeding, etc., is evaluated by a clinician.
- Severe organ involvement with any of the following symptoms
- Liver AST or ALT ≥ 1000
- CNS: impaired consciousness
- Heart and other organs failure
Who cannot join
- -
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Guatemala1 site, 1 recruiting
- Recruiting
Bio Box Guatemala Ong de Investigación, Servicios Y de Medio Ambiente
Guatemala City
Edson Jose Adrian Bolanos Lima, MD, + (502) 5414 7634, guatemala.projects@bioboxgt.org
India1 site, 1 recruiting
- Recruiting
Manipal Academy of Higher Education (MAHE)
Mangalore, Karnataka, 576104
Piya Paul Mudgal, +91 81971 71682, piya.mudgal@manipal.edu
About this study
Official title: Advancing Pandemic Preparedness: Innovative Multidisciplinary Strategies for COMBATing Severe Dengue
The goal of this observational study is to identify biomarkers and host factors associated with dengue severity in patients from dengue-endemic regions. The main question it aims to answer is:
Can multi-omics approaches predict disease severity and identify key factors contributing to severe dengue infections?
Participants will include individuals with dengue infection, and the study will analyze their blood samples using multi-omics techniques to uncover host immune responses, disease pathogenesis, and cellular pathway interactions. The study will also assess the role of primary and secondary infections, virus serotypes, and immunological factors in disease progression. Findings aim to support disease management, improve severity prediction, and identify potential therapeutic targets to prevent severe outcomes.
Read the detailed description
Background: Many ongoing dengue clinical trials aim to evaluate both therapeutic compounds and potential vaccine candidates. The therapeutic compounds aim to target various stages of dengue virus replication, such as viral entry, by inhibiting virus fusion, NS5 polymerase inhibitor, and NS1 antigenemia reduction, to mention a few. However, an omics-based approach to identifying the metabolic pathways that dengue utilizes to subvert the host system to derive energy from and subsequently deploy viral immune evasion strategies has yet to be established. This study will focus on exploring and understanding the pathways that the dengue virus exploits and investigate if blocking the identified pathway can cause the virus to 'starve.'
- The study will offer insight into the diverse system-level range of dengue infection markers and the dysregulated molecules involved in cellular and metabolic pathways during dengue infection.
- The identification of novel pathways affected by molecule dysregulation will unveil the association of the biomarkers with immune response and disease severity, thereby helping to improve patient triage and treatment.
- The identified biomarkers will be significant in monitoring patients, creating a platform for early intervention to mitigate severe dengue through novel therapeutic targets and management strategies.
The primary objectives of the proposed study are:
- Case-wise viral serotyping and investigation of host cytokine profile.
- System-wide blood-transcriptomics and proteomics during dengue infection and its relationship with disease severity.
- Identification of pathways influencing severity by in vitro mechanistic studies.
Study Cohorts:
Clinical material from two endemic regions, one from Central America (Guatemala) and Southeast Asia (India) will be used. Guatemala is an exemplary location for studying the DENV infection, owing to its distinctive combination of climatic diversity and endemic and dengue presence. Two blood samples (on the day of hospitalization and the day of discharge) from the patients will be collected as per the WHO revised 2009 case classification: 1) dengue without warning signs (DwoWS, n=200), 2) dengue with warning signs (DWS, n=200), 3) severe dengue (SD, n=200). Additionally, non-dengue samples will be collected from healthy controls (n=200). This cohort will act as the DISCOVERY cohort. We will collect whole blood in a TempusTM tube (for RNA sequencing) and serum (for proteomics and metabolomics).
Under the India-EU cooperation on research \& innovation (R\&I) and co-funding partnership under the EU framework program on R\&I 'Horizon Europe, samples will be collected from India, from Artemis Hospital, New Delhi, Max Health Care, New Delhi (a unit of Devki Devi Foundation) and Kasturba Medical College Hospital, Mangalore. Those are the two epicentres of the dengue endemic in India. 50 samples from each dengue severity classification (total samples 150 in each category) and DENV-negative healthy control (total 150: 50 in each site) will be collected. The Indian cohorts will act as the VALIDATION cohorts.
Recruitment of controls Healthy participants who have tested negative for dengue infection in the past three months will not be recruited to the study, which will be further age-and gender-matched with the cases. These samples will be tested for anti-dengue IgM and NS1 ELISA to rule out ongoing asymptomatic infection. They will also be subjected to anti-dengue IgG ELISA to check for past dengue infection. Each of the control participants will also be asked to provide a detailed medical history
- Conditions
- DENV Without Warning Signs, DENV with Warning Signs, Severe Dengue, Healthy Controls Group - Age and Sex-matched
- Being tested
- Infection and no infection
- Keywords
- Severe Dengue, Multi-omics, Predictive biomarker
- Medical subject headings
- Severe Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infection and no infectionOther
No intervention apart from the dengue infection
| Study group | Role | What they receive |
|---|---|---|
| Dengue without warning signs (DwoWS) | Laboratory confirmed Dengue without plasma leakage Receives: Other: Infection and no infection | |
| Dengue with warning signs (DWS) | Laboratory confirmed Dengue without plasma leakage plus abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing haematocrit with decreasing platelets Receives: Other: Infection and no infection | |
| Severe Dengue (SD) | Dengue with severe plasma leakage, severe bleeding, or organ failure Receives: Other: Infection and no infection | |
| Healthy Control | Healthy participants who have tested negative for dengue infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
DISCOVER predictive biomarkers and AI tool for Dengue Severity
This project aims to identify prognostic plasma protein biomarkers for disease severity in dengue virus (DENV) using data from a clinical cohort in an endemic region experiencing a surge in DENV morbidity and mortality.
It involves developing a novel consensus association-based gene/protein cooperation network to uncover key host factors driving severe disease. Additionally, the project seeks to create AI-driven prognostic tools for predicting DENV severity by integrating patient demographic and clinical data with gene and protein biomarkers, DENV serotyping, and climate information.
Measured: From enrollment to the end of hospitalisation at 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2024
- Study start3 Jan 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DENV Without Warning SignsStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- 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
- 1,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- BIO BOX GUATEMALA ONG DE INVESTIGACIÓN, SERVICIOS Y DE MEDIO AMBIENTE, DEVKI DEVI FOUNDATION SOCIETY, India, MANIPAL ACADEMY OF HIGHER EDUCATION, India, Artemis Medicare Services Ltd., India
- Responsible party
- Principal investigator, Ujjwal Neogi, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06751836
- Sponsor's protocol ID
- COMBAT (2024-05758-01)
- Other IDs
- 101191315
- Acronym
- COMBAT
- Status last verified
- Dec 2024
- First submitted
- 13 Dec 2024
- Last updated
- 10 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Annonymised and delinked IPD can be shared after the completion of the study after getting approval from the steering board and obtaining the ethical clearance of the requesting party.
Publications
Bhatt P, Varma M, Sood V, Ambikan A, Jayaram A, Babu N, Gupta S, Mukhopadhyay C, Neogi U. Temporal cytokine storm dynamics in dengue infection predicts severity. Virus Res. 2024 Mar;341:199306. doi: 10.1016/j.virusres.2023.199306. Epub 2024 Jan 6.
PubMed 38176525Mudgal PP, Veliz SPZ, Lourda M, Kadni TS, Varma M, Mazumder A, Budhiraja S, Jaggi N, Mukhopadhyay C, Sengupta S, Maitra A, Hug K, Sinha I, Ambikan AT, Filipovic I, Neogi U; COMBAT consortium. A multicenter prospective observational multi-omics study protocol to identify biomarkers for severe dengue: COMBAT study clinical protocol. BMC Infect Dis. 2026 Jul 31;26(1):1414. doi: 10.1186/s12879-026-14111-x.
PubMed 42538555
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Advancing Pandemic Preparedness: Innovative Multidisciplinary Strategies for COMBATing Severe Dengue
- ClinicalTrials.gov ID
- NCT06751836
- Acronym / sponsor ID
- COMBAT / COMBAT (2024-05758-01)
- Conditions
- DENV Without Warning Signs, DENV with Warning Signs, Severe Dengue, Healthy Controls Group - Age and Sex-matched
- Keywords
- Severe Dengue, Multi-omics, Predictive biomarker
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,400 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- BIO BOX GUATEMALA ONG DE INVESTIGACIÓN, SERVICIOS Y DE MEDIO AMBIENTE, DEVKI DEVI FOUNDATION SOCIETY, India, MANIPAL ACADEMY OF HIGHER EDUCATION, India, Artemis Medicare Services Ltd., India
- Study start
- 3 Jan 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Oct 2029 (estimated)
- First posted
- 30 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational study is to identify biomarkers and host factors associated with dengue severity in patients from dengue-endemic regions. The main question it aims to answer is:
Can multi-omics approaches predict disease severity and identify key factors contributing to severe dengue infections?
Participants will include individuals with dengue infection, and the study will analyze their blood samples using multi-omics techniques to uncover host immune responses, disease pathogenesis, and cellular pathway interactions. The study will also assess the role of primary and secondary infections, virus serotypes, and immunological factors in disease progression. Findings aim to support disease management, improve severity prediction, and identify potential therapeutic targets to prevent severe outcomes.
Detailed description
Background: Many ongoing dengue clinical trials aim to evaluate both therapeutic compounds and potential vaccine candidates. The therapeutic compounds aim to target various stages of dengue virus replication, such as viral entry, by inhibiting virus fusion, NS5 polymerase inhibitor, and NS1 antigenemia reduction, to mention a few. However, an omics-based approach to identifying the metabolic pathways that dengue utilizes to subvert the host system to derive energy from and subsequently deploy viral immune evasion strategies has yet to be established. This study will focus on exploring and understanding the pathways that the dengue virus exploits and investigate if blocking the identified pathway can cause the virus to 'starve.'
- The study will offer insight into the diverse system-level range of dengue infection markers and the dysregulated molecules involved in cellular and metabolic pathways during dengue infection.
- The identification of novel pathways affected by molecule dysregulation will unveil the association of the biomarkers with immune response and disease severity, thereby helping to improve patient triage and treatment.
- The identified biomarkers will be significant in monitoring patients, creating a platform for early intervention to mitigate severe dengue through novel therapeutic targets and management strategies.
The primary objectives of the proposed study are:
- Case-wise viral serotyping and investigation of host cytokine profile.
- System-wide blood-transcriptomics and proteomics during dengue infection and its relationship with disease severity.
- Identification of pathways influencing severity by in vitro mechanistic studies.
Study Cohorts:
Clinical material from two endemic regions, one from Central America (Guatemala) and Southeast Asia (India) will be used. Guatemala is an exemplary location for studying the DENV infection, owing to its distinctive combination of climatic diversity and endemic and dengue presence. Two blood samples (on the day of hospitalization and the day of discharge) from the patients will be collected as per the WHO revised 2009 case classification: 1) dengue without warning signs (DwoWS, n=200), 2) dengue with warning signs (DWS, n=200), 3) severe dengue (SD, n=200). Additionally, non-dengue samples will be collected from healthy controls (n=200). This cohort will act as the DISCOVERY cohort. We will collect whole blood in a TempusTM tube (for RNA sequencing) and serum (for proteomics and metabolomics).
Under the India-EU cooperation on research \& innovation (R\&I) and co-funding partnership under the EU framework program on R\&I 'Horizon Europe, samples will be collected from India, from Artemis Hospital, New Delhi, Max Health Care, New Delhi (a unit of Devki Devi Foundation) and Kasturba Medical College Hospital, Mangalore. Those are the two epicentres of the dengue endemic in India. 50 samples from each dengue severity classification (total samples 150 in each category) and DENV-negative healthy control (total 150: 50 in each site) will be collected. The Indian cohorts will act as the VALIDATION cohorts.
Recruitment of controls Healthy participants who have tested negative for dengue infection in the past three months will not be recruited to the study, which will be further age-and gender-matched with the cases. These samples will be tested for anti-dengue IgM and NS1 ELISA to rule out ongoing asymptomatic infection. They will also be subjected to anti-dengue IgG ELISA to check for past dengue infection. Each of the control participants will also be asked to provide a detailed medical history
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dengue without warning signs (DwoWS) | – | Other: Infection and no infectionLaboratory confirmed Dengue without plasma leakage |
| Dengue with warning signs (DWS) | – | Other: Infection and no infectionLaboratory confirmed Dengue without plasma leakage plus abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing haematocrit with decreasing platelets |
| Severe Dengue (SD) | – | Other: Infection and no infectionDengue with severe plasma leakage, severe bleeding, or organ failure |
| Healthy Control | – | –Healthy participants who have tested negative for dengue infection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- * Patients who are pregnant, immunocompromised, or undergoing chemotherapy, on steroids or immunosuppressive drugs in the last year, liver cirrhosis, or coinfection with a non-dengue pathogen. * Cases with a lab-confirmed dengue infection within the past three months will excluded from the case cohort.
Key inclusion criteria (19 listed)
- Group 1: Dengue without warning signs Patients presenting with the following symptoms confirmed positive for dengue infection by lab diagnosis by anti-dengue IgM or NS1 ELISA will be recruited for the study under this cohort.
- Symptoms will be fever along with at least two of the following -
- Myalgia, arthralgia
- Nausea and/or vomiting
- Rashes
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Infection and no infectionNo intervention apart from the dengue infection | Other | Dengue with warning signs (DWS), Dengue without warning signs (DwoWS), Severe Dengue (SD) |
Primary outcome
DISCOVER predictive biomarkers and AI tool for Dengue Severity
Time frame: From enrollment to the end of hospitalisation at 2 weeks
This project aims to identify prognostic plasma protein biomarkers for disease severity in dengue virus (DENV) using data from a clinical cohort in an endemic region experiencing a surge in DENV morbidity and mortality. It involves developing a novel consensus association-based gene/protein cooperation network to uncover key host factors driving severe disease. Additionally, the project seeks to create AI-driven prognostic tools for predicting DENV severity by integrating patient demographic and clinical data with gene and protein biomarkers, DENV serotyping, and climate information.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
- Background: PubMed 38176525Bhatt P, Varma M, Sood V, Ambikan A, Jayaram A, Babu N, Gupta S, Mukhopadhyay C, Neogi U. Temporal cytokine storm dynamics in dengue infection predicts severity. Virus Res. 2024 Mar;341:199306. doi: 10.1016/j.virusres.2023.199306. Epub 2024 Jan 6.
- Derived from this study: PubMed 42538555Mudgal PP, Veliz SPZ, Lourda M, Kadni TS, Varma M, Mazumder A, Budhiraja S, Jaggi N, Mukhopadhyay C, Sengupta S, Maitra A, Hug K, Sinha I, Ambikan AT, Filipovic I, Neogi U; COMBAT consortium. A multicenter prospective observational multi-omics study protocol to identify biomarkers for severe dengue: COMBAT study clinical protocol. BMC Infect Dis. 2026 Jul 31;26(1):1414. doi: 10.1186/s12879-026-14111-x.
- Individual participant dataSharing planned: Undecided. Annonymised and delinked IPD can be shared after the completion of the study after getting approval from the steering board and obtaining the ethical clearance of the requesting party.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of DENV Without Warning Signs and DENV with Warning Signs, run by Karolinska Institutet at 2 sites in 2 countries.
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 19 inclusion and 1 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 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Guatemala, India. 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?
Contact Ujjwal Neogi, PhD (+46 8524 83680, ujjwal.neogi@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DISCOVER predictive biomarkers and AI tool for Dengue Severity (time frame: From enrollment to the end of hospitalisation at 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06751836, which also lists 2 linked publications.
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 10 Feb 2025.