High Amylose Maize Starch for Treatment of Cholera
High Amylose Maize Starch for Treatment of Cholera
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.
-  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.
INCLUSION CRITERIA:

 A participant is considered eligible for participation in the trial if the following
 inclusion criteria are satisfied on admission (Day 1, before randomization) to the
 hospital:

 1. Participant is a male between 18 and 65 years of age inclusive

 2. Severe watery diarrhea without fecal blood of less than 48 hours (with passage of 3 or
 more watery stools in the 24 hours before admission)

 3. Signs of severe dehydration as per ICDDR,B guidelines (modified WHO guideline)

 4. Dipstick test/Dark-field examination positive for Vibrio cholera

 5. Written informed consent is provided

 6. Participant is willing and able to comply with all trial requirements

 EXCLUSION CRITERIA:

 A participant who meets any of the following criteria on admission (before randomization)
 to the hospital will not qualify for the study

 1. Evidence or history of any clinically significant illness as per the Investigator's
 discretion.

 2. Known case of HIV or Hepatitis B

 3. History of cancer

 4. Known renal disease

 5. Frequent excessive alcohol use, binge drinking (e.g. men consume 5 or more drinks in
 about 2 hours) or use of illicit drugs within the past two years

 6. History of receiving antimicrobial or anti-diarrheal medication (loperamide,
 diphenoxylate, etc.) within seven days of admission

 7. Concomitant infection requiring antimicrobial therapy

 8. Donated blood or plasma or experienced clinically significant loss of blood within
 eight weeks prior to admission or who plan to donate blood within 1 month after study
 participation

 9. Clinically significant abnormal laboratory test results as determined by the
 investigator

 10. Treatment within 30 days prior to admission (or five half-lives of the compound, if
 longer) with any investigational agent or device

 11. History of seizure (including febrile seizure) or loss of consciousness;

 12. History of any GI Surgery related to Bowel resections and gastric anastomoses in past
 except Appendicitis

 13. For any reason, deemed by the investigator to be inappropriate for this study,
 including participants who are unable to communicate or to cooperate with the
 investigator or designee

 14. Prior enrolment in this trial