Gut Leakage' in Dengue
ConditionsDengueDengue Hemorrhagic FeverIntestinal DiseaseAscitesDengue With Warning SignsGut Microbiome
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity of Oxford
About this trial
Dengue infections are imposing an increasing global burden of disease, particularly in tropical countries such as Bangladesh. The World Health Organization (WHO) has identified Dengue virus as a priority pathogen for the development of medical counter measures because of the high risk of it causing a Public Health Emergency of Intenational Concern (PHEIC). Warning signs for severe dengue, associated with mortality, include gastrointestinal features including abdominal pain, vomiting, and diarrhoea. Multiple alterations may occur in in the gastrointestinal tract that could lead to damaging of the gastrointestinal wall and gut leakage, the translocation of gut metabolites into the bloodstream. Study team hypothesize that gut leakage initiates inflammatory processes underlying the further development of severe dengue, including features associated with plasma leakage.
This study aims to investigate intestinal barrier dysfunction (gut leakage) in dengue infection by detecting the translocation of gut-derived bacteria and their products (Lipopolysaccharides, LPS binding protein, sCD14, I-Fatty Acid Binding Protein) into the bloodstream. Study team will recruit hospitalized adult dengue patients (18 years and older) presenting with warning signs or severe disease in a tertiary care public hospital at Chattogram, Bangladesh. Circulating biomarkers indicative of gut permeability and microbial translocation will be measured to assess their presence and association with disease severity.
Abdominal ultrasonography will be performed to characterize gastrointestinal alterations and determine their correlation with biochemical markers of gut leakage and clinical severity. In addition, study team will analyze the gut bacteriome from stool/ rectal swab of these patients to explore whether dengue infection induces compositional changes in intestinal microbiota and whether such alterations are linked to gut leakage or disease progression.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Participant/ legally authorised representative willing and able to give informed consent for participation in the study.
Male or Female, adults ≥18 years
Diagnosed as a case of Dengue on the basis of clinical features and positive NS1 antigen and/or IgM dengue antibody
Hospitalized in medicine or dengue ward in Chittagong Medical College Hospital.
Disqualifiers
Unable to provide consent or participate in follow-up procedures
Known chronic gastrointestinal (GI) disease affecting intestinal permeability (IBD, celiac disease), chronic liver disease, active chronic diarrhoea, short bowel loop syndrome, recent (<3 months) major GI surgery.
Immunosuppression (for example chemotherapy, high-dose steroids), advanced chronic kidney disease, decompensated heart failure.
Drugs that can alter the level of biomarkers in blood like metformin, statin, probiotics, steroid within last 48 hours of hospitalization.
Trial population
Adult (≥18 years) male and non-pregnant female patients with confirmed dengue (positive NS1 antigen and/or IgM) admitted to the Department of Medicine, Chittagong Medical College Hospital will be recruited. Blood biomarkers will be collected at enrollment for all patients. Those initially classified as non-severe dengue will have no repeat sampling unless they progress to severe disease, in which case a second sample will be obtained within 24 hours. Serum ALT and blood culture will be performed on day 7 of illness. Stool samples will be collected on day 7 from 100 patients for gut microbiota analysis. Additionally, 10 healthy adult participants (5 male, 5 female) will be recruited from patient attendants. They will undergo a single visit for baseline biomarker sampling and POCUS, serving as healthy controls for comparison.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
190 Participants
are grouped into 3 trial groupsGroup A: Severe dengue
Group B: Non-severe dengue
Group C: Healthy individual
Trial outcomes
Primary outcomes
1
Level of gut leakage marker in blood and gastrointestinal findings in POCUS
Time frame
On enrollment, day of development of severity if non severe at enrolment, up to 28 daysSecondary outcomes
1
Document clinical events occurred in dengue patients
Demographic: Age, gender, BMI Clinical: respiratory rate, blood pressure, heart rate, ascites, pleural effusion, any major bleeding, GCS
Time frame
Through study completion, an average of 28 days2
Document clinical events occurred in dengue patients
For mSOFA: SpO2, FiO2
Time frame
Day of enrolment/ 4th or day 7 of illnessOther outcomes
1
Level of I-FABP Level of LPS, Level of LBP, Level of sCD14, Positive Blood culture
Time frame
On enrollment in all cases, if clinical severity occur in initial non-severe group, 24 hours within developing severity2
Detectable fluid collection in abdomen, loss of haustration, loss of normal multi-layered appearance
Time frame
Baseline (within 24 hours of enrollment) and at the time of first development of clinical severity, assessed from enrollment until clinical severity occurs, hospital discharge, death, or up to 7 days of hospitalization, whichever occurs first.3
Measurement of gall bladder wall thickness, intestinal wall thickness
Time frame
Baseline (within 24 hours of enrollment) and at the time of first development of clinical severity, assessed from enrollment until clinical severity occurs, hospital discharge, death, or up to 7 days of hospitalization, whichever occurs first.4
Alteration of gut microbiota
Time frame
Day seven of illnessSponsors and contacts
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Source ClinicalTrials.gov