Travelers' DiarrheaPhase 1NCT00564863
Dose-Finding Study of CS19 Expressing ETEC Challenge Strains
A Phase 1 study testing CS19 expressing ETEC strain in people with Travelers' Diarrhea, run by Johns Hopkins Bloomberg School of Public Health at 2 sites in United States.
Trial summary
This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Travelers' Diarrhea
- What is being tested?
- CS19 expressing ETEC strain
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2007to 4 Sep 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female between 18 and 45 years of age, inclusive.
- General good health, without significant medical illness, abnormal physical examination findings or clinical laboratory abnormalities as determined by principal investigator (PI) or PI in consultation with the medical monitor and Sponsor.
- Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written examination (pass grade ≥ 70%)
- Willing to participate after informed consent obtained.
- Available for entire inpatient portion of study and all outpatient study visits.
- Negative serum pregnancy test at screening (initial visit and day -7 to - 3) and a negative urine pregnancy test on the day of admission to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Alternatively, abstinence alone is acceptable. Female subjects who are unable to bear children must provide supporting documentation (e.g., prior tubal ligation or hysterectomy).
Who cannot join
- Presence of a significant medical condition, (e.g., psychiatric conditions or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.
- Immunosuppressive illness or IgA deficiency (below the normal limits)
- Positive serology results for HIV, HBsAg, or HCV antibodies.
- Significant abnormalities in screening laboratory hematology, serum chemistry, urinalysis, as determined by PI or PI in consultation with the medical monitor and Sponsor.
- Allergy to fluoroquinolones, cotrimoxazole, or ampicillin/penicillin (excluded if allergic to two of three).
- Fewer than 3 stools per week or more than 3 stools per day as the usual frequency; loose or liquid stools other than on an occasional basis.
Show all 14Show fewer
- History of diarrhea in the 2 weeks prior to planned inpatient phase.
- Regular use of laxatives or any agent that increases gastric pH (regular defined as at least weekly).
- Use of antibiotics during the 7 days before bacterial dosing or proton pump inhibitors, H2 blockers, or antacids within 48 hours of dosing.
- Travel to countries where ETEC or cholera infection is endemic (most of the developing world) within two years prior to dosing.
- History of vaccination for or ingestion of ETEC, cholera, or LT toxin.
- Stool culture (collected no more than 1 week prior to admission) positive for ETEC or other bacterial enteric pathogens (Salmonella, Shigella and Campylobacter).
- Use of any investigational product within 30 days preceding the receipt of the challenge inoculum, or planned use during the active study period.
- Use of any medication known to affect the immune function (e.g., corticosteroids) within 30 days preceding receipt of the challenge inoculum or planned use during the active study period. (Topical and intra-articular steroids will not exclude subjects). MANAGEMENT
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Center for Immunization Research - Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, 21205
General Clinical Research Center of the Johns Hopkins Hospital
Baltimore, Maryland, 21287
About this study
Official title: Strain and Dose-Finding Study of DS26-1 and WS0115A Enterotoxigenic E. Coli (ETEC) Challenge Strains That Express CS19 Fimbriae
This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. If an 80% attack rate (AR) for predefined diarrheal disease is achieved without high output diarrhea, the same inoculum will be given to 5 - 10 more subjects for confirmation of AR. If an 80% AR is not achieved, AR and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with DS26-1 as necessary. If the WS0115A strain causes high output diarrhea, the dose will be adjusted down and further dose characterization continued. An iterative process will be used to select the optimal strain and dose with each step reviewed and approved by the medical monitor.
Read the detailed description
This is a phase 1, open-label, strain and dose-finding study designed to establish a human challenge modelfor CS19-ETEC that causes a > 80% attack rate without causing high output diarrhea. This study design is identical to that of the CS17 challenge model recently completed. Two strains of CS19-ETEC isolated from human diarrheal cases have been identified and characterized. Each clinical isolate was used to generate a cGMP MCB and procedures were established to create a fresh inoculum to administer orally in a sodium bicarbonate solution for challenge. Refer to Section 8 for full details on the isolation and preparation of these strains.
CS19-ETEC strain WS0115A (toxin phenotype of LT+ ST+ and serotype O114:H-) will be the lead strain and will be administered orally to an initial cohort of 5 subjects. This strain was isolated from the stool of a 12-month-old Egyptian girl suffering from watery diarrhea identified during a surveillance study conducted in Abees, Egypt from 1993 to 1995 by investigators at the Naval Medical Research Unit-3 (NAMRU-3), Cairo, Egypt. A negative microbiologic work-up for copathogens (other bacterialenteropathogens, rotavirus, Giardia lamblia, Entamoeba histolytica, and Cryptosporidium) supports that the isolated WS0115A strain was pathogenic in this child. Since this strain has an LT+ST+ toxin phenotype, it is the preferred strain to lead in testing the challenge model, since heterologous protection by bovine milk IgG anti-CsbD against an LT+ST+ phenotype would offer a more robust test of the protection afforded by anti-colonization. The alternate strain, CS-19 ETEC strain DS26-1 (toxin phenotype LT+ST-;serotype O8:H9) was isolated in 1990 at the U.S. Navy Forward Laboratory from a U.S. soldier with diarrhea while on deployment to Saudi Arabia during Operation Desert Shield. A negative microbiologic work-up for copathogens (Salmonella typhi, Vibrio cholerae, Giardia lamblia or Entamoeba histolytica)supports that the isolated DS26-1 strain was pathogenic in this individual. Each clinical isolate was used to generate a cGMP master cell bank and procedures were established to create a fresh inoculum to administer orally in a sodium bicarbonate solution for challenge. Refer to Section 8 for full details on the isolation and preparation of these strains.
- Conditions
- Travelers' Diarrhea
- Being tested
- CS19 expressing ETEC strain
- Keywords
- Diarrhea, ETEC
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CS19 expressing ETEC strainBiological
Wild type ETEC strain expressing the colonization faction CS19, and LT and ST enterotoxins.
| Study group | Role | What they receive |
|---|---|---|
| CS19 expressing ETEC strain | Other | Ascending dose finding study in 5-10 subjects per dose; to identify the dose able to give a diarrheal attack rate greater than or equal to 80%. Receives: Biological: CS19 expressing ETEC strain |
What is being measured
The primary outcome is the main question the study is designed to answer.
Develop of diarrhea.
Measured: 120 hours after challenge
Secondary outcomes (1)
Development of moderate to severe diarrhea
Measured: 120 hours after challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2007 (estimated)
- Study startSep 2007
- Primary completionMay 2008
- Study completion4 Sep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Travelers' DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase 1, open-label, strain and dose-finding study designed to establish a human challenge model for CS19-ETEC that causes a \> 80% attack rate without causing high output diarrhea. This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. If an 80% attack rate (AR) for predefined diarrheal disease is achieved without high output diarrhea, the same inoculum will be given to 5 - 10 more subjects for confirmation of AR. If an 80% AR is not achieved, AR and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with DS26-1 as necessary.
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Collaborators
- Naval Medical Research Center
- Responsible party
- Principal investigator, August Louis Bourgeois, Johns Hopkins Bloomberg School of Public Health
- Investigators
- Robin McKenzie, M.D., Principal investigator, Johns Hopkins Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00564863
- Sponsor's protocol ID
- CIR 240
- Other IDs
- WIRB Approval Number 20071069, Gm 100018
- Status last verified
- Apr 2017
- First submitted
- 26 Nov 2007
- Last updated
- 5 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Strain and Dose-Finding Study of DS26-1 and WS0115A Enterotoxigenic E. Coli (ETEC) Challenge Strains That Express CS19 Fimbriae
- ClinicalTrials.gov ID
- NCT00564863
- Acronym / sponsor ID
- CIR 240
- Conditions
- Travelers' Diarrhea
- Keywords
- Diarrhea, ETEC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Collaborators
- Naval Medical Research Center
- Study start
- Sep 2007 (actual)
- Primary completion
- May 2008 (actual)
- Study completion
- 4 Sep 2008 (actual)
- First posted
- 28 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. If an 80% attack rate (AR) for predefined diarrheal disease is achieved without high output diarrhea, the same inoculum will be given to 5 - 10 more subjects for confirmation of AR. If an 80% AR is not achieved, AR and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with DS26-1 as necessary. If the WS0115A strain causes high output diarrhea, the dose will be adjusted down and further dose characterization continued. An iterative process will be used to select the optimal strain and dose with each step reviewed and approved by the medical monitor.
Detailed description
This is a phase 1, open-label, strain and dose-finding study designed to establish a human challenge modelfor CS19-ETEC that causes a > 80% attack rate without causing high output diarrhea. This study design is identical to that of the CS17 challenge model recently completed. Two strains of CS19-ETEC isolated from human diarrheal cases have been identified and characterized. Each clinical isolate was used to generate a cGMP MCB and procedures were established to create a fresh inoculum to administer orally in a sodium bicarbonate solution for challenge. Refer to Section 8 for full details on the isolation and preparation of these strains.
CS19-ETEC strain WS0115A (toxin phenotype of LT+ ST+ and serotype O114:H-) will be the lead strain and will be administered orally to an initial cohort of 5 subjects. This strain was isolated from the stool of a 12-month-old Egyptian girl suffering from watery diarrhea identified during a surveillance study conducted in Abees, Egypt from 1993 to 1995 by investigators at the Naval Medical Research Unit-3 (NAMRU-3), Cairo, Egypt. A negative microbiologic work-up for copathogens (other bacterialenteropathogens, rotavirus, Giardia lamblia, Entamoeba histolytica, and Cryptosporidium) supports that the isolated WS0115A strain was pathogenic in this child. Since this strain has an LT+ST+ toxin phenotype, it is the preferred strain to lead in testing the challenge model, since heterologous protection by bovine milk IgG anti-CsbD against an LT+ST+ phenotype would offer a more robust test of the protection afforded by anti-colonization. The alternate strain, CS-19 ETEC strain DS26-1 (toxin phenotype LT+ST-;serotype O8:H9) was isolated in 1990 at the U.S. Navy Forward Laboratory from a U.S. soldier with diarrhea while on deployment to Saudi Arabia during Operation Desert Shield. A negative microbiologic work-up for copathogens (Salmonella typhi, Vibrio cholerae, Giardia lamblia or Entamoeba histolytica)supports that the isolated DS26-1 strain was pathogenic in this individual. Each clinical isolate was used to generate a cGMP master cell bank and procedures were established to create a fresh inoculum to administer orally in a sodium bicarbonate solution for challenge. Refer to Section 8 for full details on the isolation and preparation of these strains.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase 1, open-label, strain and dose-finding study designed to establish a human challenge model for CS19-ETEC that causes a > 80% attack rate without causing high output diarrhea. This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. If an 80% attack rate (AR) for predefined diarrheal disease is achieved without high output diarrhea, the same inoculum will be given to 5 - 10 more subjects for confirmation of AR. If an 80% AR is not achieved, AR and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with DS26-1 as necessary.
| Arm | Type | Receives |
|---|---|---|
| CS19 expressing ETEC strain | Other | Biological: CS19 expressing ETEC strainAscending dose finding study in 5-10 subjects per dose; to identify the dose able to give a diarrheal attack rate greater than or equal to 80%. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male or female between 18 and 45 years of age, inclusive.
- General good health, without significant medical illness, abnormal physical examination findings or clinical laboratory abnormalities as determined by principal investigator (PI) or PI in consultation with the medical monitor and Sponsor.
- Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written examination (pass grade ≥ 70%)
- Willing to participate after informed consent obtained.
- Available for entire inpatient portion of study and all outpatient study visits.
Key exclusion criteria (14 listed)
- Presence of a significant medical condition, (e.g., psychiatric conditions or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.
- Immunosuppressive illness or IgA deficiency (below the normal limits)
- Positive serology results for HIV, HBsAg, or HCV antibodies.
- Significant abnormalities in screening laboratory hematology, serum chemistry, urinalysis, as determined by PI or PI in consultation with the medical monitor and Sponsor.
- Allergy to fluoroquinolones, cotrimoxazole, or ampicillin/penicillin (excluded if allergic to two of three).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CS19 expressing ETEC strainWild type ETEC strain expressing the colonization faction CS19, and LT and ST enterotoxins. | Biological | CS19 expressing ETEC strain |
Primary outcome
Develop of diarrhea.
Time frame: 120 hours after challenge
1 secondary outcome
Development of moderate to severe diarrhea
Time frame: 120 hours after challenge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robin McKenzie, M.D. principal investigator
Johns Hopkins Bloomberg School of Public Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CS19 expressing ETEC strain in people with Travelers' Diarrhea, run by Johns Hopkins Bloomberg School of Public Health at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Develop of diarrhea. (time frame: 120 hours after challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2017; AzTrials last refreshed its copy on 30 Oct 2026.