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CompletedNCT05814042ORSUpdated Apr 14, 2026Results posted

Next Generation ORS: Comparing ORS With Calcium vs Standard ORS in Reducing Severity of Acute Watery Diarrhea

A Phase 2/3 interventional study of Next Generation ORS (oral rehydration solution) (including placebo and Current standard control ORS (oral rehydration solution) in Diarrhea and Cholera, sponsored by University of Florida. Completed at 1 site in Bangladesh. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-04-14.

Sponsored by University of Florida · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
396
Allocation
Randomized
Ages
18 Years to 60 Years
Sex
All
01

Study summary

Diarrhea remains a leading killer of children in need of better treatments.

Read the 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%.

02

Conditions studied

  • Diarrhea
  • Cholera

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03

In context

Diarrhea

877 studies on the registry are indexed under Diarrhea; 76 are open to participants now.

This study's enrollment of 396 is above the median of 137 across 738 interventional studies indexed under Diarrhea.

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Lead sponsor

University of Florida is the lead sponsor of 1,287 studies on the registry; 199 are open to participants now.

Of its 180 completed or terminated interventional studies of FDA-regulated products, 143 (79%) have results posted.

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Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
396 participants (actual)

Study arms

  • Experimental
    Nutrient based intervention

    Nutrition supplement used to stop diarrhea

    Drug: Next Generation ORS (oral rehydration solution) (including placebo

  • Active comparator
    Standard of Care oral rehydration solution

    Standard of care nutrition supplement used to stop diarrhea.

    Drug: Current standard control ORS (oral rehydration solution)

Interventions

  • DrugNext Generation ORS (oral rehydration solution) (including placebo

    Nutrition used to stop diarrhea

    Also known as: WHO Reduced Osmolarity ORS with Calcium

  • DrugCurrent standard control ORS (oral rehydration solution)

    current standard control ORS in diarrheic patients with cholera

    Also known as: WHO Reduced Osmolarity ORS

06

What researchers measure

Primary outcomes

  1. Stool Output

    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.

    Time frame: Day 1, day 2, Day 3, and entire 3 days

Secondary outcomes

  1. Duration of Diarrhea

    Duration of diarrhea was the time (in hour) from randomization until cessation of diarrhea

    Time frame: from randomization to end of treatment at day 3

  2. Stool Frequency

    Daily stool frequency was defined as the total number of diarrhea stools passed during a given 24-hour intervention day.

    Time frame: Day 1, Day 2, Day 3

  3. Vomiting

    Daily volume of vomiting was defined as the total weight of all vomitus (g) during a given 24-hour intervention day.

    Time frame: Day 1, Day 2, Day 3

  4. Percentage of Patients Who Require Unscheduled Intravenous Therapy

    Percentage of patients who require unscheduled intravenous therapy at Day1, Day 2 and Day 3 following intervention.

    Time frame: Day 1, Day 2, Day 3

  5. Intake of ORS

    Intake of ORS (ml) from randomization until cessation of diarrhea in Day 1, Day2, and Day 3.

    Time frame: Day 1, Day 2, Day 3

07

Results

Posted Apr 14, 2026
Limitations and caveats
A limitation of this study is the inability to isolate the specific effect of calcium from non-specific ORS effects. A follow-up study using a fixed dose of calcium tablets vs. placebo tablets while keeping all participants on the same standard ORS would allow more precise receptor-level exposure and minimize osmotic confounding present with Ca-ORS. Also challenging was the variability in dosage, as lower intake in mild cases or in severe cases that subsequently improve might skew the outcomes.

Participant flow

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).

Participant flow — Overall Study
MilestoneORS With Calcium (Aim 1)Standard WHO Oral Rehydration Solution (ORS; Aim 1)ORS With Calcium (Aim 2)Standard WHO Oral Rehydration Solution (ORS; Aim 2)
Started3030167169
Completed3030167169
Not completed0000

Outcome measures

PrimaryStool Output

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.

Time frame:
Day 1, day 2, Day 3, and entire 3 days
Reported as:
Mean · gram
Stool Output
gramORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2ORS With Calcium: Aim 2 (Severe Diarrhea Subset)ORS: Aim 2 (Severe Diarrhea Subset)ORS With Calcium: Aim 2 (Non-Severe Diarrhea Subset)ORS: Aim 2 (Non-Severe Diarrhea Subset)
Day 1 Stool Output4769 ± 19894742 ± 21651688 ± 18421704 ± 21674242 ± 22705008 ± 2494987 ± 803812 ± 740
Day 2 Stool Output638 ± 1116768 ± 9961326 ± 19461601 ± 2182————
Day 3 Stool Output485 ± 629360 ± 3561156 ± 18402004 ± 1604————
Total stool output5412 ± 29455581 ± 30462308 ± 34602576 ± 41274242 ± 22705008 ± 2494987 ± 803812 ± 740
Statistical analysis
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 0.9941 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.2238 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 (Severe Diarrhea Subset) vs ORS: Aim 2 (Severe Diarrhea Subset) · Wilcoxon (Mann-Whitney) · p = 0.0656 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 (Non-Severe Diarrhea Subset) vs ORS: Aim 2 (Non-Severe Diarrhea Subset) · Wilcoxon (Mann-Whitney) · p = 0.0542 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · nonparametric · p = 0.1955 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.6869 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · nonparametric · p = 0.7237 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.0911 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 1.00 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.2632 (A priori threshold for statistical significance (e.g., \< 0.05))
SecondaryDuration of Diarrhea

Duration of diarrhea was the time (in hour) from randomization until cessation of diarrhea

Time frame:
from randomization to end of treatment at day 3
Reported as:
Mean · hours
Duration of Diarrhea
hoursORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2
Duration of Diarrhea24.75 ± 9.5025.80 ± 13.0014.6 ± 16.816.4 ± 20.3
Statistical analysis
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 0.7056 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.5866 (A priori threshold for statistical significance (e.g., \< 0.05))
SecondaryStool Frequency

Daily stool frequency was defined as the total number of diarrhea stools passed during a given 24-hour intervention day.

Time frame:
Day 1, Day 2, Day 3
Reported as:
Mean · Events
Stool Frequency
EventsORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2ORS With Calcium: Aim 2 (Severe Diarrhea Subset)ORS: Aim 2 (Severe Diarrhea Subset)ORS With Calcium: Aim 2 (Non-Severe Diarrhea Subset)ORS: Aim 2 (Non-Severe Diarrhea Subset)
Stool frequency: Day 121.4 ± 9.319.0 ± 8.38.8 ± 7.49.2 ± 9.216.5 ± 9.221.4 ± 11.86.7 ± 5.15.9 ± 4.2
Stool frequency: Day 23.6 ± 3.94.2 ± 4.75.9 ± 6.17.5 ± 8.1————
Stool frequency: Day 35 ± 52.5 ± 2.45.5 ± 7.19.3 ± 13.5————
Statistical analysis
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Fisher Exact · p = 0.2733 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Fisher Exact · p = 0.8642 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 (Severe Diarrhea Subset) vs ORS: Aim 2 (Severe Diarrhea Subset) · Fisher Exact · p = 0.0339 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 (Non-Severe Diarrhea Subset) vs ORS: Aim 2 (Non-Severe Diarrhea Subset) · Fisher Exact · p = 0.3329 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Fisher Exact · p = 0.6485 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Fisher Exact · p = 0.3025 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Fisher Exact · p = 0.7168 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Fisher Exact · p = 0.1459 (A priori threshold for statistical significance (e.g., \< 0.05))
SecondaryVomiting

Daily volume of vomiting was defined as the total weight of all vomitus (g) during a given 24-hour intervention day.

Time frame:
Day 1, Day 2, Day 3
Reported as:
Mean · gram
Vomiting
gramORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2
Vomiting: Day 1313.5 ± 495283 ± 459111.4 ± 311136 ± 399
Vomiting: Day 227.7 ± 151.543.3 ± 188.958.6 ± 227.9257.2 ± 608.1
Vomiting: Day 3——221.0 ± 454.4171.8 ± 347.8
Statistical analysis
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 0.7298 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.6305 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 0.5703 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.0475 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.8452 (A priori threshold for statistical significance (e.g., \< 0.05))
SecondaryPercentage of Patients Who Require Unscheduled Intravenous Therapy

Percentage of patients who require unscheduled intravenous therapy at Day1, Day 2 and Day 3 following intervention.

Time frame:
Day 1, Day 2, Day 3
Reported as:
Count of participants · Participants
Percentage of Patients Who Require Unscheduled Intravenous Therapy
ParticipantsORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2
Percentage of patients who require unscheduled intravenous therapy: Day 14468
Percentage of patients who require unscheduled intravenous therapy: Day 21146
Percentage of patients who require unscheduled intravenous therapy: Day 30011
Statistical analysis
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Fisher Exact · p = 1.000 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Fisher Exact · p = 0.5850 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Fisher Exact · p = 1.000 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Fisher Exact · p = 0.7439 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Fisher Exact · p = 1.00 (A priori threshold for statistical significance (e.g., \< 0.05))
SecondaryIntake of ORS

Intake of ORS (ml) from randomization until cessation of diarrhea in Day 1, Day2, and Day 3.

Time frame:
Day 1, Day 2, Day 3
Reported as:
Mean · ml
Intake of ORS
mlORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2
Intake of ORS: Day 15107 ± 16165105 ± 20642992 ± 17863145 ± 2004
Intake of ORS: Day 21075 ± 11471458 ± 14712016 ± 16802451 ± 1890
Intake of ORS: Day 33250 ± 1117750 ± 11731250 ± 13723300 ± 1951
Statistical analysis
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 0.7558 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.6308 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 0.1878 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.3191 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 1 vs ORS: Aim 1 · Wilcoxon (Mann-Whitney) · p = 0.2765 (A priori threshold for statistical significance (e.g., \< 0.05))
  • ORS With Calcium: Aim 2 vs ORS: Aim 2 · Wilcoxon (Mann-Whitney) · p = 0.0007 (A priori threshold for statistical significance (e.g., \< 0.05))

Adverse events

Collected over from randomization until cessation of diarrhea, up to three days. Cessation of diarrhea will be defined as the last watery or loose stool before passage of two consecutive soft or formed stools, or the beginning of 8 consecutive hours without any stool.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ORS With Calcium: Aim 10/30 (0%)0/30 (0%)0/30 (0%)
ORS: Aim 10/30 (0%)0/30 (0%)0/30 (0%)
ORS With Calcium: Aim 20/167 (0%)1/167 (0.6%)14/167 (8.4%)
ORS: Aim 20/169 (0%)1/169 (0.6%)11/169 (6.5%)
Most frequent serious events
Most frequent serious events
EventORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2
Hypovolemic shockGastrointestinal disorders0/300/301/1671/169
Most frequent other events
Most frequent other events
EventORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2
feverGastrointestinal disorders0/300/3011/1677/169
HeartburnGastrointestinal disorders0/300/301/1673/169
Epigastric painGastrointestinal disorders0/300/302/1671/169

Baseline characteristics

Age, Continuous
Age, Continuous(years)ORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2Total
Mean31.7 ± 10.831.0 ± 10.534.0 ± 9.833.9 ± 9.733.6 ± 10.1
Sex: Female, Male
Sex: Female, Male(Participants)ORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2Total
Female346765139
Male2726100104257
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)ORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2Total
Count of participants————0
Weight
Weight(kilogram)ORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2Total
Mean52.1 ± 11.349.2 ± 12.053.3 ± 10.154.4 ± 10.453.4 ± 12.3
Correction by IV fluid (ml)
Correction by IV fluid (ml)(ml)ORS With Calcium: Aim 1ORS: Aim 1ORS With Calcium: Aim 2ORS: Aim 2Total
Mean5550 ± 10535467 ± 776591 ± 831250 ± 7071191 ± 1892
08

Study locations

1 site
  • ICDDR,B Dhaka Hospital
    Dhaka, 1212, Bangladesh
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Aug 2023 to primary completion in Dec 2024, 16 months.

Results were first posted in Apr 2026, 1 year 3 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 3, 2023
First posted
Apr 14, 2023
StartActual
Aug 21, 2023
Primary completionActual
Dec 31, 2024
CompletionActual
Dec 31, 2024
Results first posted
Apr 14, 2026
Last update
Apr 14, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 14, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05814042
Lead sponsor
University of Florida
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Sponsor
First posted
Apr 14, 2023
Start date
Aug 21, 2023
Primary completion
Dec 31, 2024
Completion
Dec 31, 2024
Results posted
Apr 14, 2026
Last update
Apr 14, 2026

Study contacts

Sam Cheng, MD. PhD
principal investigator · University of Florida

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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