Protective Immunity to Human Cholera in Bangladesh

Cholera Clinical Trial

Official title:

Protective Immunity to Human Cholera in Bangladesh-EGD Substudy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00349999
• Other study ID #: 05-0103
• Secondary ID: 5U01AI058935-14
• Status: Completed
• Phase: N/A
• First received: July 6, 2006
• Last updated: September 5, 2013
• Start date: June 2008
• Est. completion date: December 2012

Study information

• Verified date: October 2009
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bangladesh: International Centre for Diarrhoeal Disease ResearchUnited States: Institutional Review BoardUnited States: Federal GovernmentBangladesh: Ethical Review Committee
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to better understand how the body fights and protects against cholera. Two hundered fifty people presenting to the International Centre for Diarrhoeal Diseases Research, Bangladesh, admitted with acute cholera, 50 of whom (healthy, nonpregnant, 18-45 year olds) will be enrolled in this substudy of mucosal immunity involving duodenal biopsy. The remainder of the study is observational, involving collection of stool, vomit, and blood samples only. The biopsy requires a flexible tube with a camera be inserted through the mouth into the stomach and intestine. During this procedure, small samples will be collected from the intestine. The study includes medical history, physical, blood testing, hospitalization and urine pregnancy testing. This study will last for 5 years and patients will participate for 3 years.

Description:

Diarrheal diseases are some of the most common causes of morbidity and mortality in the world today. Unfortunately, effective vaccines for most of the infectious causes of diarrhea are not yet available. Vibrio cholerae (V cholerae) is an important infectious cause of severe secretory diarrhea in humans. The purpose of this study is to assess the duration of immune responses in a group of 250 individuals, aged 2-60 years, presenting to the International Centre for Diarrheal Diseases Research, Bangladesh (ICDDR,B) hospital who are admitted with acute cholera. Fifty of these participants will be enrolled in a substudy of mucosal immunity involving duodenal biopsy. This protocol focuses exclusively on the subset of 50 study participants (healthy 18-45 year old non pregnant subjects) enrolled in the substudy of mucosal immunity involving duodenal biopsy. This study is linked to DMID protocol 06-0045. The remainder of the study is observational, involving collection of stool, vomit, and blood samples only (DMID protocol 06-0045). A duodenal biopsy will be performed on enrollment or the next day and at Day 30. Twenty five subjects will undergo a third duodenal biopsy after 6 months of follow-up and 25 subjects will undergo a third duodenal biopsy after 12 months follow-up. The objectives of this study are as follows: to measure immune responses directed against Vibrio cholerae antigens and evaluate the development of anti-V cholerae memory B cells in study participants with cholera; to assess the duration of the immune responses following an episode of cholera; and to correlate the duration of antigen-specific, antibody-secreting cells for various cholera antigens in duodenal tissue with measurements of the duration of immunity based on antibody responses in serum, as well as circulating antigen-specific memory B cells. This is a single site study with a 5 year duration requiring three years of patient participation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: December 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

For the esophagogastroduodenoscopy (EGD) substudy of 50 study participants

• Admission to the International Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B) with acute cholera

• Male or nonpregnant female [pregnancy will be excluded by urine human chorionic gonadotropin (HCG) testing]

• Age 18 to 45 years, inclusive

• Residence in Dhaka city

• Provision of informed consent for enrollment in study

• Expressed interest and availability to fulfill the study requirements

Exclusion Criteria:

For the esophagogastroduodenoscopy (EGD) substudy of 50 study participants

• Participation in any other investigational drug, device or vaccine trial at present or within the past 30 days

• Known allergy to midazolam or topical anesthetics

• Presence of comorbid conditions, including:

• heart disease

• pulmonary disease

• liver disease

• kidney disease

• bleeding disorder

• neurologic disorder

• an additional intestinal disorder

• pregnancy

• anemia (hemoglobin < 12 g/dl for males or < 11 g/dl for female)

• hypotension (systolic blood pressure less than or equal to 85 mm Hg or diastolic blood pressure less than or equal to 55 mm Hg, measured in the supine position once just prior to procedure)

• hypertension (systolic blood pressure greater than or equal to 150 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg, measured in the supine position once just prior to procedure)

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cholera

Locations

Country	Name	City	State
Bangladesh	Dhaka Hospital - International Centre for Diarrhoeal Disease Research, Bangladesh	Dhaka

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum antibody responses to V cholerae Lipopolysaccharide (LPS) and Cholera Toxin, B Subunit (CTB) (and other antigens as needed) on Days 2, 7, and 30 and at Months 3, 6, 9, 12, 18, 24, 30, and 36 following enrollment.		Days 2, 7, and 30 and at Months 3, 6, 9, 12, 18, 24, 30, and 36 following enrollment.	No
Primary	Mucosal responses to V cholerae LPS and CTB (and other antigens as needed) on Days 2 and 30 (in 50 study participants) and at Month 6 (25 study participants) and Month 12 (25 study participants) following enrollment.		Days 2 and 30 (in 50 participants) and at Month 6 (25 study participants) and Month 12 (25 study participants) following enrollment.	No
Primary	Memory B and T cell responses to V cholerae LPS and CTB (and other antigens as needed) on Days 2 and 30 and at Months 3, 6, 9, 12, 18, 24, 39, and 36 following enrollment.		Days 2 and 30 and at Months 3, 6, 9, 12, 18, 24, 39, and 36 following enrollment..	No