Travelers' DiarrheaPhase 1NCT00564577
Dose-Finding Study of WS6788A and LSN03-016011/A Enterotoxigenic E. Coli ETEC Challenge Strains That Express CS17
A Phase 1 study testing CFA/I and CS17 challenge 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 LSN03-016011/A ETEC will be administered at a starting inoculum of 5x108 cfu to 5 subjects to establish a human disease model. Read more about this study
- Who is it for?
- Ages 15 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Travelers' Diarrhea
- What is being tested?
- CFA/I and CS17 challenge strain
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2006to 13 Jun 2007
- 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 15 to 45 years
- All sexes
- Healthy volunteers accepted
- Child, 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 or principal investigator 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 all planned follow-up visits.
- Negative serum pregnancy test at screening and a negative urine pregnancy test on the day of admittance 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. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g., 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 immunoglobulin A (IgA) deficiency (below the normal limits)
- Positive serology results for HIV, HBsAg, or Hepatitis C virus (HCV) antibodies.
- Significant abnormalities in screening lab hematology, serum chemistry, urinalysis or EKG (EKG in subjects ≥ 40 years), as determined by PI or PI in consultation with the medical monitor and sponsor.
- Allergy to fluoroquinolones, trimethoprim-sulfamethoxazole, 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 increase 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 CS17 + 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 and others) within 30 days preceding receipt of the challenge inoculum or planned use during the active study period.
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: Dose-Finding Study of WS6788A and LSN03-016011/A Enterotoxigenic E. Coli (ETEC) Challenge Strains That Express CS17
This will be a strain and dose-finding study in which LSN03-016011/A ETEC will be administered at a starting inoculum of 5x108 cfu to 5 subjects to establish a human disease model. If 80% attack rate (AR) is achieved without high output diarrhea, the same inoculum will be given to 10 more subjects for confirmation of AR. If 80% AR is not achieved, attack rate and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with WS6788A if applicable. If the LSN 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 model for CS17+ ETEC that causes > 80% attack rate without causing high output diarrhea. Based on the strain histories, testing will commence using LSN03-016011/A. This strain was isolated from a naïve adult U.S. citizen living in Turkey with a typical clinical presentation for ETEC diarrheal disease and no bacterial co-pathogens isolated from the stool. The host is representative of the study population for this study and for future efficacy studies with anti-CS17+ ETEC vaccines. As shown in the figure below, 5x108 cfu of ETEC strain (LSN03-016011/A) will initially be administered to 5 subjects. If an attack rate of >80% (at least 4/5 subjects) occurs with no high output diarrhea, results will be confirmed in an additional 10 subjects. Additionally, an inoculum at least ½ log lower (1x108) (depending on the severity of illness documented) may be administered to 10 subjects to characterize the dose-response relationship. If the 5x108 cfu inoculum does cause high output diarrhea, then the inoculum will be reduced appropriatelyIf the 5x108 cfu of LSN03-016011/A does not cause a > 80% attack rate, the next step will depend on the observed attack rate and severity of illness. A low attack rate with mild disease would prompt a change to the alternate strain (WS7688A) for testing, using the same pathway used with the LSN strain . An attack rate < 80% with most diarrhea classified as at least moderate diarrhea would prompt an upward adjustment of the LSN inoculum appropriate to the findings. The decision to move up or down in inoculum or to change CS17 + strains will only occur with the concurrence of the medical monitor. Following each step in the strain and dose finding iterations, a report summarizing the results of that step, and detailing the planned next step will be signed by the principal investigator and the medical monitor. The maximum dose of either strain is 1 X 109. The anticipated maximum number of subjects planned for this study is 25.
Subjects will be admitted to the inpatient facility on study day -1. On study day 0, subjects will have their morning meal, fast for 90 minutes, and then be given 120mL of sodium bicarbonate buffer to neutralize stomach acidity. Approximately one minute later they will ingest the appropriate dose and strain (either LSN03-016011/A or WS6788A ) of CS17+ ETEC diluted in 30mL sodium bicarbonate buffer. Doses of the challenge inoculum will be prepared by one of the study staff microbiologists. Treatment with antibiotics will start on study day 5, or earlier if criteria for early antibiotic treatment are fulfilled. Subjects will be discharged when they feel well and have 2 consecutive stool cultures negative for CS17+ ETEC.
For each group of 5 study subjects, the study period will include the screening period, one month for the inpatient and outpatient phases, and six-months for the final phone check. The study period, accounting for the serial scheduling of multiple groups of 5, processing immunology specimens, study analysis and report writing, is 1 ½ years.
- Conditions
- Travelers' Diarrhea
- Being tested
- CFA/I and CS17 challenge strain
- Keywords
- Diarrhea ETEC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CFA/I and CS17 challenge strainBiological
Also called Experimental
Wild type ETEC strain expressing the colonization factor CS17, and heat labile (LT) enterotoxin
| Study group | Role | What they receive |
|---|---|---|
| CFA/I and CS17 challenge strain | Other | Colonization factor antigen (CFA/I) and CS17 challenge 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%. Receives: Biological: CFA/I and CS17 challenge strain |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development 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 2006
- Primary completion13 Jun 2007
- Study completion13 Jun 2007
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.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
- 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
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 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
- Sponsor
- Investigators
- Robin McKenzie, M.D., Principal investigator, Johns Hopkins Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00564577
- Sponsor's protocol ID
- CIR 193 (B)
- Status last verified
- Apr 2017
- First submitted
- 26 Nov 2007
- Last updated
- 11 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 11 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-Finding Study of WS6788A and LSN03-016011/A Enterotoxigenic E. Coli (ETEC) Challenge Strains That Express CS17
- ClinicalTrials.gov ID
- NCT00564577
- Acronym / sponsor ID
- CIR 193 (B)
- Conditions
- Travelers' Diarrhea
- Keywords
- Diarrhea ETEC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Collaborators
- Naval Medical Research Center
- Study start
- Sep 2006 (actual)
- Primary completion
- 13 Jun 2007 (actual)
- Study completion
- 13 Jun 2007 (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 LSN03-016011/A ETEC will be administered at a starting inoculum of 5x108 cfu to 5 subjects to establish a human disease model. If 80% attack rate (AR) is achieved without high output diarrhea, the same inoculum will be given to 10 more subjects for confirmation of AR. If 80% AR is not achieved, attack rate and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with WS6788A if applicable. If the LSN 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 model for CS17+ ETEC that causes > 80% attack rate without causing high output diarrhea. Based on the strain histories, testing will commence using LSN03-016011/A. This strain was isolated from a naïve adult U.S. citizen living in Turkey with a typical clinical presentation for ETEC diarrheal disease and no bacterial co-pathogens isolated from the stool. The host is representative of the study population for this study and for future efficacy studies with anti-CS17+ ETEC vaccines. As shown in the figure below, 5x108 cfu of ETEC strain (LSN03-016011/A) will initially be administered to 5 subjects. If an attack rate of >80% (at least 4/5 subjects) occurs with no high output diarrhea, results will be confirmed in an additional 10 subjects. Additionally, an inoculum at least ½ log lower (1x108) (depending on the severity of illness documented) may be administered to 10 subjects to characterize the dose-response relationship. If the 5x108 cfu inoculum does cause high output diarrhea, then the inoculum will be reduced appropriatelyIf the 5x108 cfu of LSN03-016011/A does not cause a > 80% attack rate, the next step will depend on the observed attack rate and severity of illness. A low attack rate with mild disease would prompt a change to the alternate strain (WS7688A) for testing, using the same pathway used with the LSN strain . An attack rate < 80% with most diarrhea classified as at least moderate diarrhea would prompt an upward adjustment of the LSN inoculum appropriate to the findings. The decision to move up or down in inoculum or to change CS17 + strains will only occur with the concurrence of the medical monitor. Following each step in the strain and dose finding iterations, a report summarizing the results of that step, and detailing the planned next step will be signed by the principal investigator and the medical monitor. The maximum dose of either strain is 1 X 109. The anticipated maximum number of subjects planned for this study is 25.
Subjects will be admitted to the inpatient facility on study day -1. On study day 0, subjects will have their morning meal, fast for 90 minutes, and then be given 120mL of sodium bicarbonate buffer to neutralize stomach acidity. Approximately one minute later they will ingest the appropriate dose and strain (either LSN03-016011/A or WS6788A ) of CS17+ ETEC diluted in 30mL sodium bicarbonate buffer. Doses of the challenge inoculum will be prepared by one of the study staff microbiologists. Treatment with antibiotics will start on study day 5, or earlier if criteria for early antibiotic treatment are fulfilled. Subjects will be discharged when they feel well and have 2 consecutive stool cultures negative for CS17+ ETEC.
For each group of 5 study subjects, the study period will include the screening period, one month for the inpatient and outpatient phases, and six-months for the final phone check. The study period, accounting for the serial scheduling of multiple groups of 5, processing immunology specimens, study analysis and report writing, is 1 ½ years.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CFA/I and CS17 challenge strain | Other | Biological: CFA/I and CS17 challenge strainColonization factor antigen (CFA/I) and CS17 challenge 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
- 15 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, 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 or principal investigator 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 all planned follow-up 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 immunoglobulin A (IgA) deficiency (below the normal limits)
- Positive serology results for HIV, HBsAg, or Hepatitis C virus (HCV) antibodies.
- Significant abnormalities in screening lab hematology, serum chemistry, urinalysis or EKG (EKG in subjects ≥ 40 years), as determined by PI or PI in consultation with the medical monitor and sponsor.
- Allergy to fluoroquinolones, trimethoprim-sulfamethoxazole, 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 |
|---|---|---|
| CFA/I and CS17 challenge strainAlso: ExperimentalWild type ETEC strain expressing the colonization factor CS17, and heat labile (LT) enterotoxin | Biological | CFA/I and CS17 challenge strain |
Primary outcome
Development 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 11 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 CFA/I and CS17 challenge 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 11 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?
Development 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 11 Apr 2017.