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Therapeutic Induction of Endogenous Antibiotics

This study has been completed.
Sponsor:
Collaborators:
Swedish International Development Cooperation Agency (SIDA)
Karolinska Institutet
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier:
NCT00800930
First received: December 2, 2008
Last updated: December 6, 2011
Last verified: December 2008
  Purpose

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
Shigellosis
Biological: Sodium Butyrate
Biological: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Therapeutic Induction of Endogenous Antibiotics for Improved Recovery in Shigellosis

Resource links provided by NLM:


Further study details as provided by International Centre for Diarrhoeal Disease Research, Bangladesh:

Primary Outcome Measures:
  • The primary endpoints of the study is to assess the efficacy of sodium butyrate enema in adult patients with shigellosis in marked improvement in clinical, endoscopic and histological findings. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To study the effect of sodium butyrate on the induction of endogenous antibiotic peptides in the rectum in adults with shigellosis. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: January 2005
Study Completion Date: January 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
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.
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.
Placebo Comparator: 2
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.
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18-55 years of age
  • duration of diarrhoea 0-4 days
  • culture-confirmed Shigella spp (all Shigella spp) in stool on enrolment

Exclusion Criteria:

  • who received antimicrobial treatment before attending the ICDDR,B hospital
  • clinical symptoms of other concomitant infections (such as chronic respiratory infections, other concomitant gastrointestinal infections)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00800930

Locations
Bangladesh
Dhaka Hospital & Matlab Hospital
Dhaka, Bangladesh, 1212
ICDDR,B
Dhaka, Bangladesh, 1212
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Swedish International Development Cooperation Agency (SIDA)
Karolinska Institutet
Investigators
Principal Investigator: Rubhana Raqib, Ph.D. International Centre for Diarrhoeal Disease Research, Bangladesh
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT00800930     History of Changes
Other Study ID Numbers: 2004-031
Study First Received: December 2, 2008
Last Updated: December 6, 2011
Health Authority: Bangladesh: Ethical Review Committee

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
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.

Additional relevant MeSH terms:
Dysentery, Bacillary
Bacterial Infections
Digestive System Diseases
Dysentery
Enterobacteriaceae Infections
Gastroenteritis
Gastrointestinal Diseases
Gram-Negative Bacterial Infections
Intestinal Diseases
Butyric Acid
Histamine Agents
Histamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014