Experimental Human Infection With Neisseria Gonorrhoeae (LptA Trial)
Condition: Gonococcal Infection
MeSH terms: Infections; Communicable Diseases; Gonorrhea
Intervention: Azithromycin; Ceftriaxone; Ciprofloxacin; Neisseria gonorrhoeae strain FA1090 A26; Neisseria gonorrhoeae strain FA7527
Intervention description: Alternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics.; Mandatory antibiotic treatment failure therapy: Ceftriaxone 250 mg intramuscular 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 on patient request, at the onset of symptoms or on the 5th study day after inoculation.; 0.4 mL of a suspension containing 10^5 - 10^6 CFU of wild-type (WT) 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 isogenic LptA mutant Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.
Intervention MeSH terms: Azithromycin; Ciprofloxacin; Ceftriaxone
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: Male
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ceftriaxone; challenge; ciprofloxacin; males; Neisseria gonorrhoeae

Summary:

      This is a Phase 1, interventional, non-randomized, experimental infection model study in
      healthy adult males (N=up to 25) between the ages of 18-35 at study enrollment. The study is
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for
      gonococcal infection in the male urethra through infection with engineered mutants of N.
      gonorrhoeae. We predict that mutations abolishing expression of N. gonorrhoeae virulence
      determinants will eliminate or significantly reduce gonococcal infectivity or the ability to
      induce inflammation in an infected individual, thus identifying potential vaccine candidates.
      Study duration will be 1 year, and the duration for all participants will be about 3 weeks.
      The primary objective of the study is to compare the ability of different engineered mutants
      of Neisseria gonorrhoeae to cause a clinical infection (signs or symptoms of urethritis such
      as discomfort during urination, urethral discharge, etc.) in the male urethra.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy man between the ages of 18 and 35 years.

          2. Able and willing to be located easily by providing street address and telephone number
             (land line and/or cell phone number).

          3. Willingness to provide written informed consent.

          4. Able and willing to attend all study visits including 6-day stay in the Clinical and
             Translational Research Center (CTRC) during the trial (with ability to leave the unit
             during the day) and follow-up visit during the week after treatment.

          5. Able and willing to abstain from masturbation during the 6-day stay in the CTRC.

          6. Able and willing to abstain from all sexual activity during the course of the study.

          7. Acceptable medical history by screening evaluation.

          8. Standard physical exam within normal limits (WNL).

          9. Serum creatinine WNL.

         10. Serum alanine transaminase (ALT) WNL.

         11. White blood cell (WBC), polymorphonuclear cell (PMN) and hemoglobin values WNL.

         12. Normal urinalysis.

         13. Total Complement (CH50) WNL.

         14. Urine negative for chlamydia, gonorrhea, trichomonas and mycoplasma.

         15. Negative HIV, syphilis, and Hepatitis C (HCV) test results.

         16. Negative Hepatitis B (HBV) core and surface antibodies or results consistent with
             immunization (negative HBV core antibody/positive HBV surface antibody).

         17. Denies history of STIs including syphilis and hepatitis B & C.

         18. Denies history of bleeding diathesis.

         19. Denies history of seizures (due to reports of seizures with ciprofloxacin).

         20. Denies history of cancer, except basal cell carcinoma of the skin more than 5 years
             ago.

         21. Denies history of drug abuse.

         22. Denies history of psychiatric disorders, except depression controlled by medication.

         23. Denies history of genitourinary surgery.

        Exclusion Criteria:

          1. Student or employee under the direct supervision of any of the study investigators.

          2. Any known immunodeficiencies including complement deficiency, antibody deficiency,
             chronic granulomatous disease or HIV infection.

          3. Psychiatric disorders that would interfere with the integrity of the data or volunteer
             safety.

          4. Unstable depression (defined as receiving either < 3 months of the same medication
             (and dose) or a decompensating event during the previous 3 months) or depression that,
             in the opinion of the investigator, will compromise the subject's ability to comply
             with protocol requirements.

          5. Heart murmur or heart disease.

          6. Anatomic abnormality of the urinary tract.

          7. Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days.

          8. Chemotherapy within the past year.

          9. Current steroid use, except for topical application.

         10. Allergy to penicillin, ceftriaxone or ciprofloxacin or to lidocaine.

         11. Treatment with medications that are contraindicated with ciprofloxacin or ceftriaxone
             and that cannot be withheld for the single doses given in this study.