Clinical Trial: Efficacy of Benefiber-Added, Reduced-Osmolarity WHO-ORS in the Treatment of Cholera in Adults

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Efficacy of Benefiber-Added, Reduced-Osmolarity WHO-ORS in the Treatment of Cholera in Adults

Brief Summary: In cholera, the function of small intestine is affected resulting in increased secretion of electrolytes and water and their reduced absorption leading to profuse watery diarrhoea. The human colon has the capacity to absorb water and electrolytes. A number of recent studies have shown that short chain fatty acids (SCFAs) such as acetate, butyrate and propionate stimulates absorption of sodium in the colon, which is not affected by cyclic AMP. It has also been shown that SCFAs inhibits c-AMP mediated chloride secretion in the colon. Benefiber (partially hydrolyzed guar gum) is water soluble fibre, and when added to ORS it undergoes fermentation in the colon liberating SCFAs. SCFAs not only serves as metabolic fuel to the enterocytes but they also enhance colonic absorption of salts and water. Thus, they have potentials to reduce the severity of diarrhoea in patients with cholera. The aim of this study is to assess the efficacy of Benefiber-added WHO-ORS in the management of adults with cholera. In this randomized, controlled clinical trial, a total of 174 adult males with cholera would be studied. Study patients would be selected from those who attend the Dhaka Hospital of ICDDR,B with a history of diarrhoea of less than 24 hours and signs of severe dehydration. They would be rehydrated using intravenous fluid (cholera saline) over 4 hrs during which a stool specimen would be subjected for dark-field microscopy for identification of V. cholerae. Those identified to have cholera would be randomized in equal numbers to receive either: a) Benefiber (25 g/L) added WHO-ORS, b) Benefiber (50 g/L) added to the new formulation (Na+ 75, glucose 75, Cl- 65, K+ 20 mmol/L, citrate 10 mmol/L, osmolarity 245 mosmol/L) of WHO-ORS , or c) the same WHO-ORS but without Benefiber for maintenance of hydration until resolution of diarrhoea. All patients would be treated with a single, 300 mg dose of doxycycline capsules and would be provided with the standard hospital diets. Fluid intake

Detailed Summary:

Considerable interest has recently been generated on dietary fibers (DF), and soluble fibers have emerged both as a subject for research and therapeutic applications. The 'fiber hypothesis', put forward by Denis Bukitt and Hugh Trowel (1-4), suggests that consumption of unrefined carbohydrate food protects against many western ailments including colon cancer, diverticular disease, appendicitis, constipation, haemorrhoids, diabetes, heart disease, gall stones, and obesity among others. In the line of this hypothesis, many basic laboratory and clinical works have been done. The term 'dietary fiber' has been used to denote plant polysaccharides and lignin that are resistant to hydrolysis by human digestive enzymes (5,6). The detailed chemistry and metabolism of DF have also been studied (7-10). The classification of fiber is based on their chemical structures (11), and they can be divided into non-polysaccharides and non-starch polysaccharides. Lignin is the only non-polysaccharide fiber, which is a polymer of phenolic alcohol that is water insoluble. The non-starch polysaccharide can be divided into cellulose and non-cellulose fiber. Cellulose consists of un-branched D-glucose chains in 1,4-ß linkage and is water insoluble. Non-cellulose polysaccharides include hemicelluloses, mucillages, gums and pectins, and they consists of various ß linkages of wide variety of hexose and pentose sugars. The polysaccharide chains are heteroglycans (chains with more than one type of monosaccharide). The hemicellulosic materials are polymers of xylose, mannose and glucose with side chains of galactose and arabinose. The pectic substances are polymers of galacturonic acids. Likewise, the gums and mucillages are branched carbohydrate polymers (e.g. gum, which is a linear mannan with galactose side chains). Non-cellulose polysaccharides vary in degree of their water solubilities (7,9,10).

Same as current

Current Secondary Outcome: ORS intake and duration of diarrhoea, Clinical success (and failure), success (and failure) of oral rehydration therapy, and the proportion of patients requiring "unscheduled intravenous fluid therapy" [ Time Frame: 24 months ]

Original Secondary Outcome: Same as current

Information By: International Centre for Diarrhoeal Disease Research, Bangladesh

Dates:
Date Received: May 3, 2008
Date Started: May 2003
Date Completion:
Last Updated: May 5, 2008
Last Verified: December 2004