Cholera, Diarrhea
Conditions
Brief summary
Diarrhea remains a leading killer of children in need of better treatments.
Detailed description
Diarrhea remains a leading killer of children in need of better treatments. Oral Rehydration Solution (ORS) is currently the only oral therapy that is recommended for children with acute diarrhea. Although it is valuable for correcting dehydration and is considered the primary reason for the substantial reduction in mortality from diarrhea in children, ORS does not have the capacity to "halt" intestinal fluid loss and thus, does not offer a rapid relief of a child's diarrhea symptom, and its use by caregivers and medical practitioners has markedly dropped (estimate use in 1/3 of cases who need it). In recognition of its limitations, continuous efforts have been made to modify the composition of ORS. However, none has targeted the central diarrhea-causing pathways and produced a satisfactory outcome in children. New therapeutic approaches and methods are needed. The proposed new ORS is based on recent discovery of the first inclusive antidiarrheal mechanism in the intestine, CaSR (calcium-sensing receptor) that targets all known diarrhea causing pathways. It works in animals. This R21 is the 1st proof-of-concept clinical study in humans and is intended to investigate its safety and efficacy. Two Specific Aims are proposed to determine new ORS safety and efficacy in patients with diarrhea. In the safety study, the investigators propose to enroll 396 diarrheal adults (198 in Intervention New ORS group and 198 in standard WHO ORS). In the efficacy study, the investigators plan to enroll 396 diarrheal adults (198 in Intervention New ORS group and 198 in standard WHO ORS, these will be same patients employed for the safety study). These diarrheal patients will be recruited from the Dhaka area in Bangladesh. At the conclusion of the study, we expect to develop a novel oral rehydrating solution that is inexpensive and practical to use in all the countries. Hypothesis: the volume output Intervention should reduce stool weight/output of diarrhea by 30%.
Interventions
DRUGNext Generation ORS (oral rehydration solution) (including placebo
Nutrition used to stop diarrhea
DRUGCurrent standard control ORS (oral rehydration solution)
current standard control ORS in diarrheic patients with cholera
Sponsors
University of Florida
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Two groups: Control vs Intervention
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Adult male and female patients, age between 18 and 60 years, history of acute watery diarrhea (defined as the passage of ≥3 loose or watery stools in the past 24 hours) for less than 24 h before admission, either signs of severe dehydration and stool positive for Vibrio cholerae, and successful rehydration with intravenous fluids within the first 6 h after admission (cholera group), or signs of some dehydration and stool negative for V. cholera (non-cholera group) , and successful rehydration with intravenous or oral fluids within the first 6 h
Exclusion criteria
* Pregnancy as determined by history of last menstrual period, bloody diarrhea, signs of systemic infection that needed intravenous antibiotics, or inability to rehydrate with intravenous fluid therapy in the first 6 h after admission.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stool Output | Day 1, day 2, Day 3, and entire 3 days | Daily stool output was defined as the total weight of all stools (g) passed during a given 24-hour intervention day. Total stool output was defined as the cumulative weight of all stools (g) passed over the entire 72-hour study period or until diarrhea resolved, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Diarrhea | from randomization to end of treatment at day 3 | Duration of diarrhea was the time (in hour) from randomization until cessation of diarrhea |
| Stool Frequency | Day 1, Day 2, Day 3 | Daily stool frequency was defined as the total number of diarrhea stools passed during a given 24-hour intervention day. |
| Vomiting | Day 1, Day 2, Day 3 | Daily volume of vomiting was defined as the total weight of all vomitus (g) during a given 24-hour intervention day. |
| Percentage of Patients Who Require Unscheduled Intravenous Therapy | Day 1, Day 2, Day 3 | Percentage of patients who require unscheduled intravenous therapy at Day1, Day 2 and Day 3 following intervention. |
| Intake of ORS | Day 1, Day 2, Day 3 | Intake of ORS (ml) from randomization until cessation of diarrhea in Day 1, Day2, and Day 3. |
Countries
Bangladesh
Contacts
PRINCIPAL_INVESTIGATORSam Cheng, MD. PhD
University of Florida
Participant flow
Recruitment details
Over a period of 18-24 months, we recruit: Severely dehydrated 60 adult patients (≥18 to ≤60 yrs), duration \<24hrs, with cholera (n=30/group x 2 groups) (Aim 1). In parallel, adults ((≥18 to ≤60 yrs) with non-V. cholera (RDT/cholkit dipstick negative) non-bloody acute diarrhea with 'Some' dehydration (n=167/group and 169/group; 2 groups), a total of 336 patients. (Aim 2).
Pre-assignment details
Work Flow: Triage =\>ER/SSU: Step 1: Verbal Consent, Study Nurse (SN)/ Field Research Supervisor (FRS) put a tag on bed and write screening ID on top of Study CRF=\>Study Ward/Allocated Space: Step 2: HW Screening Form; Step 3: FRS if enrollment criteria met consent done; Step 4: SN Complete admission section of CRF including clinical signs of dehydration; Step 5: Randomization to 72h or till diarrhea cease=\> Discharge Step-6: SN/PRP record outcome; Step 7: FRS Follow up at enrollment day 7.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 10.1 |
| Correction by IV fluid (ml) | 250 ml STANDARD_DEVIATION 707 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 257 Participants |
| Weight | 52.1 kilogram STANDARD_DEVIATION 11.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 | 0 / 167 | 0 / 169 |
| other Total, other adverse events | 0 / 30 | 0 / 30 | 14 / 167 | 11 / 169 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 1 / 167 | 1 / 169 |
Outcome results
None listed