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Sponsors and Collaborators: |
International Centre for Diarrhoeal Disease Research, Bangladesh Swedish International Development Agency (SIDA) Karolinska Institutet |
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Information provided by: | International Centre for Diarrhoeal Disease Research, Bangladesh |
ClinicalTrials.gov Identifier: | NCT00800930 |
Shigellosis is one of the major causes of morbidity and mortality in many developing countries. The continued emergence of antibiotic resistant strains has complicated the treatment of shigellosis and has increased the cost of treatment markedly. Antimicrobial peptides are considered as endogenous antibiotic. A mixture of these antimicrobial peptides (LL-37 and beta-defensin) drenches the mucosal epithelial surfaces forming a barrier for invading microorganisms. Recently, we found that Shigella down-regulates the expression of LL-37 and beta-defensin 1 (HBD-1) in the colon of patients during acute shigellosis thereby facilitating bacterial invasion. Both LL-37 and HBD-1 could inhibit the growth of various microbes e.g. S. dysenteriae type 1, S. flexneri, and S. boydii. Our study indicated that bacterial DNA might be a potential mediator for the down- regulation in vitro. Down-regulation of LL-37 and HBD-1 was also seen in watery diarrhea caused by other pathogens. Thus, bacteria-mediated down-regulation of our front line defenses could be one strategy evolved by the pathogens to subvert this host-defense mechanism. gene encoding LL-37 in cultured epithelial cell lines were up-regulated when treated with butyrate; butyrate decreased the severity of Shigella infections in rabbit model. We could reproduce our findings from human i.e. downregulation of CAP-18 (the rabbit homologue to human LL-37) in colon epithelia after infection with Shigella flexneri. CAP-18 reappeared after treatment of the infected rabbits with sodium butyrate. Thus, the rabbit model demonstrated the proof of principal. In this study, we aim to assess the efficacy of sodium butyrate enema in reduction of clinical symptoms and / severity, reduction of inflammatory responses and induction of endogenous antibiotic activity in the rectum in adult patients with shigellosis.
Condition | Intervention | Phase |
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Shigellosis |
Biological: Sodium Butyrate Biological: Saline |
Phase II |
Study Type: | Interventional |
Study Design: | Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Therapeutic Induction of Endogenous Antibiotics for Improved Recovery in Shigellosis |
Estimated Enrollment: | 120 |
Study Start Date: | January 2005 |
Estimated Study Completion Date: | January 2009 |
Estimated Primary Completion Date: | December 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Active Comparator
Patients will be instructed to lie on a bed (cholera cot) in left lateral position. A soft rectal catheter will be introduced by a nurse/physician, through which 80 ml of butyrate solution will be instilled slowly with a 50 ml plastic syringe. Patients will be asked to retain the enema for at least ½ hour by remaining supine for 30 minutes after the administration. However, if a patient cannot retain the enema for 30 minutes, he will be given a second round of enema immediately after defecation.
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Biological: Sodium Butyrate
Patients will be instructed to lie on a bed (cholera cot) in left lateral position. A soft rectal catheter will be introduced by a nurse/physician, through which 80 ml of butyrate solution will be instilled slowly with a 50 ml plastic syringe. Patients will be asked to retain the enema for at least ½ hour by remaining supine for 30 minutes after the administration. However, if a patient cannot retain the enema for 30 minutes, he will be given a second round of enema immediately after defecation.
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2: Placebo Comparator
Patients will be instructed to lie on a bed (cholera cot) in left lateral position. A soft rectal catheter will be introduced by a nurse/physician, through which 80 ml of saline solution will be instilled slowly with a 50 ml plastic syringe. Patients will be asked to retain the enema for at least ½ hour by remaining supine for 30 minutes after the administration. However, if a patient cannot retain the enema for 30 minutes, he will be given a second round of enema immediately after defecation.
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Biological: Saline
Patients will be instructed to lie on a bed (cholera cot) in left lateral position. A soft rectal catheter will be introduced by a nurse/physician, through which 80 ml of saline solution will be instilled slowly with a 50 ml plastic syringe. Patients will be asked to retain the enema for at least ½ hour by remaining supine for 30 minutes after the administration. However, if a patient cannot retain the enema for 30 minutes, he will be given a second round of enema immediately after defecation.
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Ages Eligible for Study: | 18 Years to 45 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Rubhana Raqib, Ph.D. | 8860523-32 ext 2404 | rubhana@icddrb.org |
Bangladesh | |
ICDDR,B | Recruiting |
Dhaka, Bangladesh, 1212 | |
Contact: Rubhana Raqib, Ph. D. 8860523-32 ext 2404 rubhana@icddrb.org | |
Dhaka Hospital & Matlab Hospital | Recruiting |
Dhaka, Bangladesh, 1212 | |
Contact: Rubhana Raqib, Ph. D. 8860523-32 ext 2404 rubhana@icddrb.org | |
Sub-Investigator: Birgitta Agerberth, Ph. D. | |
Sub-Investigator: Jan Andersson, Ph. D. |
Principal Investigator: | Rubhana Raqib, Ph.D. | International Centre for Diarrhoeal Disease Research, Bangladesh |
Responsible Party: | International Centre for Diarrhoeal Disease Research, Bangladesh ( Dr. Rubhana Raqib ) |
Study ID Numbers: | 2004-031 |
Study First Received: | December 2, 2008 |
Last Updated: | December 3, 2008 |
ClinicalTrials.gov Identifier: | NCT00800930 |
Health Authority: | Bangladesh: Ethical Review Committee |
Shigellosis sodium butyrate antimicrobial peptides LL-37 innate immunity |
The aims are to assess efficacy of sodium butyrate enema in marked improvement in clinical features endoscopic findings histological features Induction of LL-37 in the rectum. |
Bacterial Infections Signs and Symptoms Digestive System Diseases Shigellosis Gastrointestinal Diseases Dysentery |
Enterobacteriaceae Infections Dysentery, Bacillary Intestinal Diseases Gastroenteritis Gram-Negative Bacterial Infections |