Clinical trial NCT01823952: High Amylose Maize Starch for Treatment of Cholera
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.
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Diarrhea
Keywords: HAMS
ORS
Cholera
Diarrhea
Lead sponsor: PATH
Sponsor class: OTHER
First posted: 2013-04-04
Enrollment: 106
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Sampling method: PROBABILITY_SAMPLE
Study population: Study Population is 150 adult male patients: 40 each in the HAMS, HAMSA2.5 and HAMSA6 arms and 30 in the HO-ORS study arm.

Brief summary: 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.

Detailed description: * 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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of Diarrhea
timeFrame: 12 hrs w/o diarrhoea, up to max of 96 hrs
Secondary outcomes:
measure: Stool output and fluid intake rate
timeFrame: 0 to 96 hrs
Other outcomes:
measure: Safety & Tolerability as measured by adverse events, vital signs and lab parameters
timeFrame: Approximately 24 hours after randomization
Locations:
city: Mohakhali
country: Bangladesh
facility: Dhaka Hospital - icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh)
state: Dhaka
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Nur H Alam, MD MBBS
role: PRINCIPAL_INVESTIGATOR
References: