Clinical Trial: Enteroaggregative E.Coli (EAEC)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Pathogenicity of Enteroaggregative E. Coli in Adult Volunteers; Dose-Escalation Study

Brief Summary: Enteroaggregative E. coli (EAEC) is a bacterium that can cause diarrhea. The purposes of this study are to: determine how much EAEC is needed to cause diarrhea in a healthy person, determine if a genetic factor is important in causing diarrhea, and to see how the body's defenses control EAEC. Participants include 25 healthy adults, ages 18-40. Volunteers will be assigned to 1 of 4 dose levels in groups of 5 volunteers each. One volunteer in each group will receive a sodium bicarbonate placebo solution. Volunteers will be admitted to the University Clinical Research Unit for up to 8 days. Volunteers will receive therapy with levofloxacin to treat the infection either once they develop diarrhea or at Day 5 if they remain asymptomatic. Study procedures will include saliva, blood, and fecal sample collection. An optional study procedure will include an intestinal biopsy. Participants will be involved in study related procedures for up to 223 days.

Detailed Summary: Enteroaggregative Escherichia coli (EAEC) causes diarrhea in travelers from industrialized nations to developing countries, children of developing countries, and patients with HIV. Although infection responds to antibiotic therapy, increasing antibiotic resistance and the widespread nature of the infection limit the utility of antibiotics. The development of an EAEC-specific vaccine would be useful in the prevention of travel-associated EAEC diarrhea and in the decrease of EAEC-associated mortality in young children in the US and of developing countries. The first objective of the study is to perform a dose-escalation study of EAEC 042 infectivity in healthy adult volunteers who are high producers of IL-8 and seronegative to EAEC. The study will identify the dose of EAEC 042 needed for future studies on EAEC 042 such as phase I-II EAEC vaccine studies. The second objective of the study is to identify the humoral, secretory, and cellular immune response to EAEC 042 specific antigens that are associated with EAEC infection. Study participants will include 25 healthy volunteers, ages 18-40, from the greater Houston area. Study participants will be assigned to 1 of 4 possible dose levels in groups of 5 volunteers each. Each study group will consist of 4 volunteers receiving EAEC and 1 volunteer receiving a sodium bicarbonate placebo solution. Safety data and results will be reviewed by the safety monitoring committee before beginning the next highest dose group. If a dose results in at least 3 of the 4 infected volunteers of a given group, the next highest dose will not be administered. Instead, the concentration will be repeated for validation of the dose. Healthy volunteers will be screened as outpatients for the presence of the -251 AA SNP genotype in the IL-8 gene promoter. Once a volunteer has been screened and determined to be eligible to participate in the study, the volunteer will sign a consent form and be admitted at the University Clinical Research Unit. The
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome: Development of diarrhea defined as passage of one diarrheal stool containing at least 300 mL or 2 or more stools totaling 200 mL or greater passed during a 48-hour period within 96 hours after challenge. [ Time Frame: Assessed daily during the inpatient portion of the study ]

Original Primary Outcome:

Current Secondary Outcome:

  • Increases in individual markers of inflammation: fecal leukocytes, lactoferrin and pro-inflammatory cytokines. [ Time Frame: At the conclusion of the challenge studies, once all specimens have been collected. ]
  • Proportion of subjects who receive rescue antibiotic therapy (defined as the initiation of antibiotic therapy when the primary outcome criteria listed above is met). [ Time Frame: Assessed daily during the inpatient portion of the study, Days 0-8 ]
  • Secretory IgA and humoral IgG response to homologous administered strain; expressed in titers. [ Time Frame: At the conclusion of the challenge studies, once all specimens have been collected. ]
  • Total volume of unformed stools passed during 5 days of study. [ Time Frame: Assessed daily during the inpatient portion of the study ]
  • Positive excretion of the administered test strain and number of days of excretion before antimicrobial is administered. [ Time Frame: Assessed daily during the inpatient portion of the study ]
  • Development of mild diarrhea defined as passage of any number of stools categorized as loose or watery but of less than 200 mL in addition to a complaint of one or more enteric symptoms. [ Time Frame: Assessed daily during the inpatient portion of the study ]


Original Secondary Outcome:

Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: August 10, 2006
Date Started: February 2008
Date Completion:
Last Updated: December 22, 2016
Last Verified: April 2010