High Amylose Maize Starch for Treatment of Cholera (RESTORS)
A randomized, double-blind trial in adult males with acute dehydrating diarrhea of cholera comparing the safety, tolerability and efficacy of HAMS HO-ORS, HAMS 2.5% Acetate HO-ORS, HAMS 6% Acetate HO-ORS and HO-ORS.
The primary hypothesis is that at least one of the hypo-osmolar ORS containing high amylose maize starch 6% acetate (HAMSA6-HO-ORS), hypo-osmolar ORS containing high amylose maize starch 2.5% acetate (HAMSA2.5-HO-ORS) and a hypo-osmolar ORS containing high amylose maize starch (HAMS-HO-ORS), will significantly reduce diarrhea duration compared with hypo-osmolar (HO) ORS.
Specifically, the investigators expect that HAMSA6 will be the most effective preparation.
|Official Title:||Phase 2, Single Centre, Randomized, Double-blind Study Conducted in Adult Males With Acute Dehydrating Diarrhea Due to Cholera With the Aim Being to Select One or More of the Three Fermentable Starches (FS) for an FS-HO-ORS Formulation.|
- Duration of Diarrhea [ Time Frame: 12 hrs w/o diarrhoea, up to max of 96 hrs ] [ Designated as safety issue: No ]
Duration of diarrhea during the study period (defined as time from randomisation to the last watery stool preceding two soft/formed stools or a 12 hour period without diarrhea, up to a maximum of 96 hours)
- Stool output and fluid intake rate [ Time Frame: 0 to 96 hrs ] [ Designated as safety issue: No ]
- Total output of watery stool (g/kg body weight)
- Weight of watery stool
- Intake of oral fluids including ORS and plain water in mL/kg from time of randomization to the first soft/formed stool or 48 hours of treatment with study products, whichever is sooner
- Proportion of patients who vomit in the first 24 hours
- Proportion of patients who require unscheduled intravenous fluids post randomization
- Amount (mL/kg) of unscheduled intravenous fluids required post randomization
- Proportion of patients with diarrhea beyond 48 hours
- Safety & Tolerability as measured by adverse events, vital signs and lab parameters [ Time Frame: Approximately 24 hours after randomization ] [ Designated as safety issue: Yes ]
- Proportion of patients with biochemical and symptomatic hyponatremia
- Proportion of patients with adverse events deemed possibly or definitely related to treatment with the investigational products
- Proportion of patients with abnormal biochemical and haematological values (any grade 3 as per CTCAE version IV criteria or above)
- Proportion of patients with serious adverse events deemed possibly or definitely related to treatment with investigational products
Biospecimen Retention: Samples Without DNA
Analysis of the sample for starch, short chain fatty acids and faecal microbiota.
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
- Burden: Watery diarrhea including cholera continues to be a major cause of childhood mortality in developing countries, with an estimated 1.5 million children dying each year. This figure has greatly reduced from approximately 5 million diarrheal deaths annually 20 years ago, a phenomenon often attributed to the utilization of oral rehydration solution (ORS).
- Knowledge Gap: ORS is very effective in correcting dehydration and reducing mortality, but is not adequately used in many countries, partly due to the fact that it does not reduce diarrhea. The physiological basis for ORS is that glucose-stimulated sodium and fluid absorption is not inhibited by cyclic 3',5'-adenosine monophosphate (cAMP) and other diarrhea mediators which inhibit sodium chloride absorption. The conventional glucose-based ORS does not reduce duration or severity of diarrhea and may in fact paradoxically increase fecal fluid losses. Advances in ORS composition have included the universal adoption of hypo-osmolar ORS (HO-ORS) in 2003. Recent technological innovations have led to the use of amylase-resistant starches and their modifications in the treatment of diarrhea. Short chain fatty acids (SCFA), which are produced in colon from these non-absorbed carbohydrates, enhance sodium absorption. An orally administered, non-absorbed starch (i.e., one resistant to digestion by amylase) significantly reduced fecal fluid loss and the duration of diarrhea in patients with cholera.
- Relevance: Efforts are continuing to improve the efficacy of oral rehydration solution. As glucose stimulates sodium and water absorption in small intestine, short chain fatty acids (SCFAs) stimulate sodium and water absorption in the colon. In cholera, colonic function is also impaired due to the lack of SCFAs. The main source of SCFAs is the unabsorbed carbohydrates that are fermented in the colon by the colonic bacteria. The maize starch contains substantial amount of amylase resistant starch that escapes digestion and absorption in the small intestine and is fermented in the colon, liberating SCFAs. We expect that our experimental ORS containing maize starch will reduce the severity (stool volume) and enhance recovery (reduce duration) of diarrhoea.
|Contact: Sonali Kochhar||(91-11) 2653 firstname.lastname@example.org|
|Contact: Evan Simpsonemail@example.com|
|Dhaka Hospital - icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh)||Recruiting|
|Mohakhali, Dhaka, Bangladesh, 1212|
|Contact: Nur H Alam, MD, MBBS 8802 8860520 ext 2345 firstname.lastname@example.org|
|Contact: Mohammed A Salam, MBBS 88 01711547903 email@example.com|
|Principal Investigator: Nur H Alam, MD, MBBS|
|Sub-Investigator: Mohammed A Salam, MBBS|
|Sub-Investigator: Hasan Ashraf, MD MBBS MCPS|
|Sub-Investigator: Tahmeed Ahmed, PhD, MBBS|
|Principal Investigator:||Nur H Alam, MD MBBS||International Centre for Diarrhoeal Disease Research, Bangladesh|