Human Challenge Model With ST-only Enterotoxigenic Escherichia Coli

NCT02870751 | Unknown Phase 1 DMC

• 1 other identifier: NRC234364
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Heat stable toxin (ST) producing ETEC strains are important causes of childhood diarrhea in many countries. Vaccine candidates targeting ST are in development. A human challenge model using an epidemiologically relevant enterotoxigenic E.coli (ETEC) strain expressing ST, but not other diarrhea inducing toxins like heat labile toxin (LT), is necessary to perform an early and efficient evaluation of an ST-toxoid based vaccine. In this controlled human infection study the investigators will assess the safety of a ST-only producing ETEC strain and the dose needed to achieve an attack rate of 70% in healthy human volunteers.

Conditions

Diarrhea, Infantile

Keywords

ETEC; human challenge study; heat stable toxin; tourist diarrhea; diarrhea; enterotoxigenic

Outcome Measures

Primary Outcomes (2)

• Diarrheal disease

  5 days

• Adverse event monitoring

  30 days

Secondary Outcomes (1)

• Immune responses towards challenge strain

  2 years

Study Arms (1)

ST-only ETEC strain TW11681 or TW10722

EXPERIMENTAL

Oral inoculum of several doses of bacteria to establish range to achieve diarrhea attack rate in around 70% of volunteers.

Biological: TW11681 or TW10722

Interventions

TW11681 or TW10722 BIOLOGICAL

ST-only ETEC strain TW11681 or TW10722

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent before initiation of any study procedures.
• Healthy as judged by the Principal Investigator (PI) and determined by medical history, physical examination, and medication history.
• Within 15 days of vaccination, have normal screening laboratories for white blood cells (WBC), hemoglobin (Hgb), platelets, absolute neutrophil count (ANC), sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), C-reactive protein (CRP).
• Demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination (passing grade is at least 80 percent).
• Capable of understanding, consenting and complying with the entire study protocol.
• Female subjects must be of non-childbearing potential, (as defined as surgically sterile or postmenopausal for more than 1 year), or if of childbearing potential must be practicing abstinence or using an effective licensed method of birth control (e.g., history of hysterectomy or tubal ligation; use hormonal or barrier birth control such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), cervical sponges, diaphragms, condoms with spermicidal agents, or must have a vasectomized partner) within 2 months of infection and must agree to continue such precautions during the study and for 30 days after the Day 56 study visit. Male subjects must agree not to father a child for 90 days after the Day 28 study visit. A woman is eligible if she is monogamous with a vasectomized male.
• Agrees not to participate in another clinical trial during the study period.

You may not qualify if:

• Women who are pregnant or lactating or have a positive serum pregnancy test at screening or positive urine pregnancy test upon admission to inpatient facility.
• Abnormal Vital signs, defined as:
• Hypertension (systolic blood pressure \>140 mm Hg or diastolic blood pressure \>90 mm Hg) at rest on 2 separate days; or (heart rate \<55 at rest on 2 separate days)
• Respiratory rate \>17
• Temperature \>/= 38.0 C (100.4 F) or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within 7 days of inoculum.
• Active positive Hepatitis B, C, and Human Immunodeficiency Virus (HIV) serologies.
• History of antimicrobial treatment in the 2 weeks before bacterial inoculum
• Received previous experimental E. coli, LT, or cholera vaccines or live E. coli or Vibrio cholerae challenges; or previous infection with cholera or diarrheagenic E. coli.
• Abnormal bowel habits as defined by fewer than 3 stools per week or more than 2 stools per day in the past 6 months.
• History of chronic gastrointestinal illness, including severe dyspepsia (mild or moderate heartburn or epigastric pain occurring no more than 3 times per week is permitted), lactose intolerance, or other significant gastrointestinal tract disease.
• Regular use (weekly or more often) of laxatives, anti-diarrheal, anti-constipation, or antacid therapy.
• History of major gastrointestinal surgery, excluding uncomplicated appendectomy or cholecystectomy.
• Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal and topical steroids are allowed).
• Have a diagnosis of schizophrenia or other major psychiatric diagnosis.
• Receiving the following psychiatric drugs: aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, molindone, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, chlorprothixene, chlorpromazine, perphenazine, trifluopromazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate

Sponsors & Collaborators

• University of Bergen: lead
• University of Maryland: collaborator
• Haukeland University Hospital: collaborator

Study Sites (1)

Haukeland University Hospital

Bergen, Hordaland, 5021, Norway

RECRUITING

Related Publications (6)

• Skrede S, Steinsland H, Sommerfelt H, Aase A, Brandtzaeg P, Langeland N, Cox RJ, Saevik M, Wallevik M, Skutlaberg DH, Tellevik MG, Sack DA, Nataro JP, Guttormsen AB. Experimental infection of healthy volunteers with enterotoxigenic Escherichia coli wild-type strain TW10598 in a hospital ward. BMC Infect Dis. 2014 Sep 4;14:482. doi: 10.1186/1471-2334-14-482.

  PMID: 25190096 BACKGROUND

• Aase A, Sommerfelt H, Petersen LB, Bolstad M, Cox RJ, Langeland N, Guttormsen AB, Steinsland H, Skrede S, Brandtzaeg P. Salivary IgA from the sublingual compartment as a novel noninvasive proxy for intestinal immune induction. Mucosal Immunol. 2016 Jul;9(4):884-93. doi: 10.1038/mi.2015.107. Epub 2015 Oct 28.

  PMID: 26509875 BACKGROUND

• Sahl JW, Steinsland H, Redman JC, Angiuoli SV, Nataro JP, Sommerfelt H, Rasko DA. A comparative genomic analysis of diverse clonal types of enterotoxigenic Escherichia coli reveals pathovar-specific conservation. Infect Immun. 2011 Feb;79(2):950-60. doi: 10.1128/IAI.00932-10. Epub 2010 Nov 15.

  PMID: 21078854 BACKGROUND

• Steinsland H, Lacher DW, Sommerfelt H, Whittam TS. Ancestral lineages of human enterotoxigenic Escherichia coli. J Clin Microbiol. 2010 Aug;48(8):2916-24. doi: 10.1128/JCM.02432-09. Epub 2010 Jun 9.

  PMID: 20534806 BACKGROUND

• Rim S, Sakkestad ST, Zhou F, Gullaksen SE, Skavland J, Chauhan SK, Steinsland H, Hanevik K. Dynamics of circulating lymphocytes responding to human experimental enterotoxigenic Escherichia coli infection. Eur J Immunol. 2023 Aug;53(8):e2250254. doi: 10.1002/eji.202250254. Epub 2023 Jun 28.

  PMID: 37102399 DERIVED

• Sakkestad ST, Steinsland H, Skrede S, Lillebo K, Skutlaberg DH, Guttormsen AB, Zavialov A, Paavilainen S, Soyland H, Saevik M, Heien AR, Tellevik MG, Barry E, Langeland N, Sommerfelt H, Hanevik K. A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+ T cell responses. PLoS Negl Trop Dis. 2019 Oct 30;13(10):e0007823. doi: 10.1371/journal.pntd.0007823. eCollection 2019 Oct.

  PMID: 31665141 DERIVED

MeSH Terms

Conditions

Diarrhea, Infantile; Diarrhea

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Halvor Sommerfelt, MD, PhD

  Centre for International Health, University of Bergen

  STUDY CHAIR

Central Study Contacts

Kurt Hanevik, MD, PhD

CONTACT

+4793856690; kurt.hanevik@med.uib.no

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PostDoc, Principal investigator

Study Record Dates

• First Submitted: August 13, 2016
• First Posted: August 17, 2016
• Study Start: May 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: September 1, 2019
• Last Updated: September 11, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share

Locations

NO (1)