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

Next Generation ORS: Randomized Controlled Trial Comparing ORS With Calcium vs Standard ORS in Reducing Severity With Acute Watery Diarrhea in Adults

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

Study Overview

• Status: Recruiting
• Conditions: Diarrhea; Cholera
• Intervention / Treatment: Drug: Next Generation ORS (oral rehydration solution) (including placebo; Drug: Current standard control ORS (oral rehydration solution)

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%.

• Study Type: Interventional
• Enrollment (Estimated): 396
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Shafiqul Sarker, MD; Phone Number: 88-01713039813; Email: sasarker@icddrb.org

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1212
    • Recruiting
    • icddr,b Dhaka Hospital
    • Contact: Shafiqul Sarker, MD; Email: sasarker@icddrb.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nutrient based intervention; Nutrition supplement used to stop diarrhea	Drug: Next Generation ORS (oral rehydration solution) (including placebo; Nutrition used to stop diarrhea; Other Names: WHO Reduced Osmolarity ORS with Calcium
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); current standard control ORS in diarrheic patients with cholera; Other Names: WHO Reduced Osmolarity ORS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool Volume Output	Stool output is defined as the weight of stool in g per kg bodyweight after initial intravenous and or oral hydration	Year 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of diarrhea	Duration of diarrhea is the time (in hour) from randomization until cessation of diarrhea	year 2
Stool frequency	stool frequency is defined as the number of stool per day	year 2
Percentage of patients who vomit	Percentage of patients who vomit from randomization until cessation of diarrhea	year 2
Percentage of patients who require unscheduled intravenous therapy	Percentage of patients who require unscheduled intravenous therapy from randomization until cessation of diarrhea	year 2
Intake of ORS	Intake of ORS (ml) from randomization until cessation of diarrhea	year 2

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Sam Cheng, MD. PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Diarrhea; Cholera; Pharmaceutical Solutions
• Other Study ID Numbers: IRB202202746 -N -R; 1R21AI169282-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No