Enteroaggregative E.Coli (EAEC)

NCT00362869 | Terminated Phase 1

• 2 other identifiers: 02-209UTHSC-H UCRC 1-5-03-023
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Escherichia Coli Infections

Keywords

Enteroaggregative Escherichia coli, diarrhea, challenge

Outcome Measures

Primary Outcomes (1)

• 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.

  Assessed daily during the inpatient portion of the study

Secondary Outcomes (6)

• Increases in individual markers of inflammation: fecal leukocytes, lactoferrin and pro-inflammatory cytokines.

  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).

  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.

  At the conclusion of the challenge studies, once all specimens have been collected.

• Total volume of unformed stools passed during 5 days of study.

  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.

  Assessed daily during the inpatient portion of the study

Study Arms (5)

1

EXPERIMENTAL

Dosage 1X10\^9 given orally in a sodium bicarbonate solution

Drug: Levofloxacin; Drug: Placebo; Biological: Enteroaggregative E. coli (EAEC)

2

EXPERIMENTAL

Dosage 5X10\^9 given orally in a sodium bicarbonate solution

Drug: Levofloxacin; Drug: Placebo; Biological: Enteroaggregative E. coli (EAEC)

5

PLACEBO COMPARATOR

Sodium bicarbonate placebo solution

Drug: Levofloxacin; Drug: Placebo

4

EXPERIMENTAL

Dosage 5X10\^10 given orally in a sodium bicarbonate solution

Drug: Levofloxacin; Drug: Placebo; Biological: Enteroaggregative E. coli (EAEC)

3

EXPERIMENTAL

Dosage 1X10\^10 given orally in a sodium bicarbonate solution

Drug: Levofloxacin; Drug: Placebo; Biological: Enteroaggregative E. coli (EAEC)

Interventions

Levofloxacin DRUG

Administered at a dose of 500 mg once a day for 3 days

1; 2; 3; 4; 5

Placebo DRUG

Sodium bicarbonate solution

1; 2; 3; 4; 5

Enteroaggregative E. coli (EAEC) BIOLOGICAL

Dosages: 1X10\^9, 5X10\^9, 1X10\^10, and 5X10\^10 cfu; given in a sodium bicarbonate solution

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sign an Institutional Review Board-approved consent prior to any study-related activities.
• Initiate screening 21± 7 days prior to admission or enrollment.
• Must accomplish all laboratory and diagnostic examinations at 21± 7 days prior to admission or enrollment.
• Be at least 18 years of age but not older than 40 years of age at the time of enrollment.
• Be otherwise healthy with a stable address and telephone where the volunteer can be contacted.
• Be able to read and write English.
• Possess a social security number in order to receive compensation.
• Female participants must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the morning of the challenge and use effective birth control during the entire study period. Methods of effective birth control include: complete abstinence, the use of a licensed hormonal method, intrauterine device, barrier method plus spermicide, or having sexual relations exclusively with a vasectomized partner. Appropriate barrier methods include condoms, cervical sponge, and diaphragm. Females who are not of childbearing potential are defined as those who are physiologically incapable of becoming pregnant, including any female with tubal ligation or who is postmenopausal. For purposes of this study, postmenopausal status will be defined as absence of menses for at least 1 year.
• Be seronegative for antibodies to dispersin.
• Have normal laboratory screening values including a white blood cell (WBC) count, hemoglobin, hematocrit, platelets, blood urea nitrogen, glucose, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), quantitative immunoglobulins, T cell subsets (CD4 and CD8), urinalysis.
• Have normal chest x-ray and electrocardiogram.
• Have negative serologies for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV), and a negative rapid plasma reagin (RPR).
• Have a negative stool examination for pathogenic ova and pathogenic parasites, and bacterial enteropathogens (EAEC, Salmonella, Shigella, Campylobacter).
• Have the -251 AA IL-8 genotype.

You may not qualify if:

• Has acute or chronic medical illness (i.e., renal or hepatic disease, hypertension, diabetes mellitus, coronary artery disease, malnutrition, obesity (body mass index \>30 kg/m2), HIV, corticosteroid use, cancer or receiving chemotherapy, chronic debilitating illness, syphilis).
• Has used antibiotics within 7 days of challenge.
• Has used medications or drugs, including over-the-counter medications such as decongestants, antacids (calcium carbonate or aluminum-based antacids, H2 blockers), anti-diarrheal medications (such as bismuth subsalicylate or loperamide), antihistamines within 7 days of challenge.
• Has a history of chronic gastrointestinal illness, intra-abdominal surgery, chronic functional dyspepsia, chronic gastroesophageal reflux, documented peptic ulcer disease, gastrointestinal hemorrhage, gallbladder disease, inflammatory bowel disease (Crohn's and ulcerative colitis), diverticulitis, irritable bowel syndrome or frequent diarrhea.
• Has a history any of the following psychiatric illness(es):
• Depression not controlled with current drug therapy or involving institutionalization
• Schizophrenia or psychosis
• Suicide attempt.
• Has a history of or current alcohol or illicit drug abuse.
• Is unable to remain as an inpatient in the University Clinical Research Unit for up to 8 days.
• Has a known hypersensitivity to latex, heparin, opiates, antiemetics, benzodiazepines, lidocaine, magnesium citrate, or Fleet enema.
• Has a known hypersensitivity to antibiotics that could be used to treat EAEC infection including fluoroquinolones, amoxicillin, cephalosporins or rifaximin.
• Has serum antibodies to EAEC dispersin.
• Recently traveled to a developing country (within 6 months).
• Has household contacts who are less than 4 years of age or more than 80 years of age.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Escherichia coli Infections; Diarrhea

Interventions

Levofloxacin; heat stable toxin (E coli)

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2006
• First Posted: August 15, 2006
• Study Start: February 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: December 1, 2008
• Last Updated: December 26, 2016

Record last verified: 2010-04

Locations

US (1)