Experimental Human Rhinovirus Infection

NCT01823640 | Completed Phase 1 DMC

• 1 other identifier: EHRVI
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Our primary objective is to set up the Human Rhinovirus (HRV)-model in our centre. In addition, to facilitate future clinical trials, we want to determine optimal read-out parameters and read-out time points for experimental HRV infection in healthy volunteers. Furthermore, we want to analyze to what extent HRV can cause systemic immune effects, and we want to test if subjects with antibodies against HRV can be re-infected with the same virus, and if the presence of HRV antibodies influences the local clinical and immunological response upon infection. Additionally, to gain insight in the immune modulating properties of HRV, we want to investigate the immunological response to a HRV re-infection within one week to determine if there are mechanisms that provide immediate protection against re-infection. This facilitates a cross-over design of future pharmacological intervention-trials. Furthermore, we want to investigate the capacity of HRV infection to modulate the systemic immune response by analyzing the response of leukocytes ex vivo stimulated with different stimuli. Moreover, we want to evaluate the effects of HRV-16 infection on the host transcriptome and metabolome. Finally, The influence of HRV-16 infection on nasal and gut microbiota will be assessed.

Conditions

Common Cold

Keywords

HRV; Pharmacodynamics / kinetics; Resistance

Outcome Measures

Primary Outcomes (1)

• The main study parameter is the rate of infection (defined by a positive viral culture, qPCR and/or a four-fold rise in antibody titre) caused by HRV-16 inoculation.

  up to day 28 (qPCR)

Secondary Outcomes (9)

• duration of the incubation period

  inbetween day 0 (inoculation) and day 28

• the effects of HRV-16 (re-)infection on cold symptoms and temperature

  day 0 - day 28

• the effects of HRV-16 (re-)infection on spirometry

  day 0 t/m day 4, day 7 t/m day 11. Day 14, 28

• Leukocyte counts and differentiation (NK-cells, CD4 / CD8, neutrophils), and cytokine levels in nasal washes (including but not limited to IL-8, IL-1β, CCL5)

  day 0 t/m day 4, day 7 t/m day 11. Day 14, 28

• Leukocyte counts and circulating plasma cytokines (including but not limited to TNF-α, IL-6, IL-10, IFN-γ, IL-8, CCL5)

  day 0 t/m day 4, day 7 t/m day 11. Day 14, 28

Study Arms (2)

Placebo-HRV

EXPERIMENTAL

inoculation with placebo followed by inoculation with HRV

Other: placebo; Other: Human Rhinovirus strain 16 (HRV-16)

HRV-HRV

EXPERIMENTAL

inoculation with HRV followed by a second inoculation with HRV

Other: Human Rhinovirus strain 16 (HRV-16)

Interventions

placebo OTHER

Placebo-HRV

Human Rhinovirus strain 16 (HRV-16) OTHER

100 TCID50 dosis of HRV-16 will be inoculated on day 7 and / or day 0

HRV-HRV; Placebo-HRV

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥18 and ≤35 years of age
• Healthy
• Use of contraceptives (for female subjects only)

You may not qualify if:

• Pregnancy or lactating
• Pre-existent lung disease, including asthma
• A history of allergic rhinitis with positive allergen skin tests
• Use of any medication
• Use of alcohol \> 5/day or \>20/wk
• Use of any drugs
• Current smoker or more than 5 pack-year history
• Frequently have nosebleeds
• Recent nasal or otologic surgery
• Febrile illness or a common cold within four weeks before the HRV challenge
• Currently participating in another clinical trial

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6525 HB, Netherlands

Location

MeSH Terms

Conditions

Common Cold

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Nijmegen Medical Centre, The Netherlands

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2013
• First Posted: April 4, 2013
• Study Start: March 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2014
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

NL (1)