Brief Title
Protective Immunity to Human Cholera in Bangladesh
Official Title
Protective Immunity to Human Cholera in Bangladesh-EGD Substudy
Brief 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.
Detailed 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.
Study Type
Observational
Primary Outcome
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.
Condition
Cholera
Study Arms / Comparison Groups
1
Description: 18 males and non pregnant females, ages 18-45, with acute cholera.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
125
Start Date
June 2008
Completion Date
December 2012
Primary Completion Date
January 2012
Eligibility Criteria
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)
Gender
All
Ages
18 Years - 45 Years
Accepts Healthy Volunteers
No
Contacts
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Location Countries
Bangladesh
Location Countries
Bangladesh
Administrative Informations
NCT ID
NCT00349999
Organization ID
05-0103
Secondary IDs
5U01AI058935-14
Study Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor
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Verification Date
October 2009