Experimental Human Infection With Neisseria Gonorrhoeae
Condition: Gonococcal Infection
MeSH terms: Infections; Communicable Diseases; Gonorrhea
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1, interventional, non-randomized, experimental infection model study with
      healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for
      gonococcal infection in the male urethra. The duration for all participants will be about 3
      weeks. Study duration will be approximately about 18 months for implementation and
      enrollment. The primary objectives of the present study are to: (1) compare infectivity of
      different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections
      and to (2) assess relative fitness of the mutant in competitive infections initiated by
      inocula containing equivalent numbers of both WT and mutant strains for mutants with WT
      infectivity.
    

Detailed description: 
      This is a Phase 1, interventional, non-randomized, experimental infection model study with
      healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for
      gonococcal infection in the male urethra. For each mutant to be investigated under this
      protocol, groups of subjects will be enrolled first in noncompetitive infection studies:
      Group 1 (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant
      N. gonorrhoeae strain, and Group 2 (n = up to 8) will receive a bacterial inoculum containing
      only the wild-type (WT) N. gonorrhoeae strain. If primary and secondary outcomes are not
      different for the isogenic mutant and WT strains, a group of subjects will be enrolled in
      competitive infection studies: Group 3 (up to 16) will receive a bacterial inoculum
      containing a mixture of equivalent numbers the isogenic mutant and WT strain. All subjects
      will be examined daily for symptoms of infection and receive antibiotic treatment at the end
      of the inpatient portion of the trial. Within 7 days of antibiotic treatment, subjects will
      return for a follow-up examination. A final follow-up phone interview will be conducted
      within 2 weeks of antibiotic treatment. The duration for all participants will be about 3
      weeks. Study duration will be approximately about 18 months for implementation and
      enrollment. The primary objectives of the present study are to: (1) compare infectivity of
      different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections
      and to (2) assess relative fitness of the mutant in competitive infections initiated by
      inocula containing equivalent numbers of both WT and mutant strains for mutants with WT
      infectivity. Note, competitive infections will not be performed if non-competitive infections
      are substantially different. If this is the case, there will be no analysis for this primary
      objective. The study secondary objective is to compare the clinical course of infection with
      mutant and WT N. gonorrhoeae in noncompetitive infections.
    

Intervention name(s): Cefixime; Ceftriaxone; Ciprofloxacin; Neisseria gonorrhoeae strain FA1090 A26; Neisseria gonorrhoeae strain FA7537
Intervention type(s): Drug; Drug; Drug; Biological; Biological
Intervention description(s): Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.; Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.; Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the subject has a positie test of cure 1 week post initial antibiotic treatment; 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.; 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter
Intervention MeSH terms: Ciprofloxacin; Ceftriaxone; Cefixime
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: ceftriaxone; challenge; ciprofloxacin; males; Neisseria gonorrhoeae