Challenge Non-Typhoidal Salmonella (CHANTS) Study

NCT05870150 | Active Not Recruiting DMC

• 3 other identifiers: 21HH698930165921/PR/0051
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol describes the challenge non-typhoidal Salmonella (CHANTS) study. This is a first-in-human phase 1, double-blinded, randomised, dose-escalation human infection study, conducted in healthy volunteers aged 18 to 50 years. The primary objective of the study is to perform a dose escalation with two strains (ST19 or ST313) to determine the infectious dose required for 60-75% of volunteers to develop Salmonellosis using a composite diagnostic criterion. The secondary objectives of the study are to describe and compare the clinical and laboratory features following controlled human infection. It is hoped that the successful establishment of an NTS human challenge model can be used in the future to test candidate vaccines for NTS disease.

Conditions

Salmonella Infections; Salmonella Typhimurium; Non-typhoidal Salmonella (NTS); Invasive Non-Typhoidal Salmonella Disease; Communicable Disease; Infections, Bacterial; Enteric Fever (Not Typhoid); Gastroenteritis

Keywords

Controlled human infection study; Human infection challenge model; Experimental human challenge

Outcome Measures

Primary Outcomes (1)

• The dose in CFU of Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium) 4/74 and D23580 strains required for 60-75% of volunteers to develop systemic Salmonellosis following oral challenge

  The proportion of participants who develop either: Fever ≥38°C on ≥2 occasions ≥12 hours apart AND/OR Salmonella Typhimurium bacteraemia

  Up to Day 14 post challenge (Inclusive)

Secondary Outcomes (28)

• The Salmonella colonisation rate following oral challenge with Salmonella Typhimurium 4/74 and D23580 strains at different doses

  Up to Day 14 post challenge (Inclusive)

• The Salmonella gastroenteritis rate following oral challenge of Salmonella Typhimurium 4/74 and D23580 strains at different doses.

  Up to Day 14 post challenge (Inclusive)

• The persistent fever rate following oral challenge with Salmonella Typhimurium 4/74 and D23580 at different doses.

  Up to Day 14 post challenge (Inclusive)

• The rate of systemic Salmonellosis according to an alternative composite diagnostic criterion following oral challenge of Salmonella Typhimurium 4/74 and D23580 at different doses.

  Up to Day 14 post challenge (Inclusive)

• The safety of oral challenge with S. Typhimurium 4/74 and D23580 strains

  Up to Day 14 post challenge (Inclusive)

Other Outcomes (5)

• To investigate how the human microbiota interacts with oral challenge of S. Typhimurium 4/74 or S. Typhimurium D23580 strains

  Up to Day 365 post challenge (Inclusive)

• To investigate novel diagnostic methods for detecting S. Typhimurium infection

  Up to Day 365 post challenge (Inclusive)

• To describe and compare additional host immune responses following oral challenge of S. Typhimurium 4/74 or S. Typhimurium D23580 strains.

  Up to Day 365 post challenge (Inclusive)

Study Arms (2)

ST19

EXPERIMENTAL

Healthy volunteers will be challenged with Salmonella Typhimurium ST19

Biological: Salmonella Typhimurium

ST313

EXPERIMENTAL

Healthy volunteers will be challenged with Salmonella Typhimurium ST313

Biological: Salmonella Typhimurium

Interventions

Salmonella Typhimurium BIOLOGICAL

Salmonella Typhimurium oral challenge. Dose-escalating (1-5x10\^3 CFU, 1-5x10\^4 CFU, 1-5x10\^5 CFU, 1-5x10\^6 CFU)

ST19; ST313

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must satisfy all the following criteria to be considered eligible for the study:
• Agree to give informed consent for participation in the study.
• Aged between 18 and 50 years inclusive at time of challenge.
• In good health as determined by medical history, physical examination, and clinical judgment of the study team.
• Agree (in the study team's opinion) to comply with all study requirements, including capacity to adhere to good personal hygiene and infection control precautions.
• Agree to allow his or her General Practitioner (and/or Consultant if appropriate), to be notified of participation in the study.
• Agree to allow study staff to contact his or her GP to access the participant's medical history and vaccination records.
• Agree to allow UKHSA and the local health protection unit to be informed of their participation in the study.
• Agree to give his or her close contacts written information informing them of the participant's involvement in the study and offer them voluntary screening for Salmonella carriage.
• Agree to a period of inpatient quarantine whilst symptomatic (In exceptional circumstances, the duration of inpatient quarantine may be extended.)
• Agree to have 24-hour contact with study staff during the four weeks post challenge and can ensure that they are contactable by mobile phone for the duration of the study period until antibiotic completion.
• Agree to allow the study team to hold the name and 24-hour contact number of a close friend, relative or housemate who will be kept informed of the study participant's whereabouts for the duration of the challenge period after quarantine (from the time of challenge until completion of antibiotic course). This person will be contacted if study staff are unable to contact the participant after discharge from inpatient quarantine.
• Have internet access to allow completion of the e-diary and real-time safety monitoring.
• Agree to avoid antipyretic/anti-inflammatory treatment from the time of challenge (Day 0) until advised by a study doctor or until 14 days after challenge.
• Agree to refrain from donating blood for the duration of the study.

You may not qualify if:

• The participant will not be enrolled if any of the following apply:
• History of microbiologically confirmed Salmonella infection.
• History of significant organ-specific and/or systemic disease that could interfere with trial conduct or completion. Including, for example, but not restricted to:
• Cardiovascular disease, including specifically Atherosclerotic disease Stable or unstable angina Previous myocardial infarction Valvular heart disease Vascular disease, including specifically
• Documented aneurysmal arterial disease
• Peripheral arterial disease
• Endovascular prosthesis oRespiratory disease
• Haematological disease including sickle cell disease and sickle cell trait.
• Endocrine disorders, including specifically diabetes mellitus
• Renal or bladder disease, including history of renal calculi
• Biliary tract disease, including specifically biliary colic, asymptomatic gallstones, or previous cholecystectomy
• Gastro-intestinal disease including specifically, a current requirement for antacids, H2-receptor antagonists, proton pump inhibitors or laxatives OR Inflammatory bowel disease OR Confirmed diagnosis of irritable bowel syndrome as defined by the Rome IV criteria.
• Neurological disease
• Metabolic disease
• Autoimmune disease

Sponsors & Collaborators

• Imperial College Healthcare NHS Trust: lead
• University of Oxford: collaborator
• University of Liverpool: collaborator
• PATH: collaborator
• Imperial College London: collaborator

Study Sites (1)

Imperial College London

London, England, W2 1NY, United Kingdom

Location

Related Publications (1)

• Smith C, Smith E, Rydlova A, Varro R, Hinton JCD, Gordon MA, Choy RKM, Liu X, Pollard AJ, Chiu C, Cooke GS, Gibani MM. Protocol for the challenge non-typhoidal Salmonella (CHANTS) study: a first-in-human, in-patient, double-blind, randomised, safety and dose-escalation controlled human infection model in the UK. BMJ Open. 2024 Jan 10;14(1):e076477. doi: 10.1136/bmjopen-2023-076477.

  PMID: 38199617 DERIVED

Related Links

• Study website

MeSH Terms

Conditions

Salmonella Infections; Communicable Diseases; Bacterial Infections; Typhoid Fever; Gastroenteritis

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections and Mycoses; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A two-arm study where participants will receive one of two strains of Salmonella Typhimurium (ST19 or ST313).

Study Record Dates

• First Submitted: May 3, 2023
• First Posted: May 23, 2023
• Study Start: August 31, 2023
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Locations

GB (1)