Experimental Human Infection With Neisseria Gonorrhoeae

• Status: Completed
• Trial end date: 2019-11-25
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Cefixime; Ceftriaxone; Ciprofloxacin

Criteria

Inclusion Criteria:

1. Healthy man > / = 18 and < 36 years old

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 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 all sexual activity until completion of the study and the follow-up test for gonorrhea is negative

6. Acceptable medical history by screening evaluation

7. No clinically significant abnormalities on physical exam

8. Urinalysis: leukocyte esterase, and White Blood Cell (WBC) values within normal limits (WNL)

9. CH50 WNL

10. Urine negative for chlamydia, gonorrhea, and trichomonas

11. Negative Human Immunodeficiency Virus (HIV), syphilis, and Hepatitis C (HCV) test results

12. Negative Hepatitis B (HBV) core and surface antibodies or results consistent with immunization (negative HBV core antibody/positive HBV surface antibody)

13. Denies history of Sexually Transmitted Infections (STIs) including gonorrhea, chlamydia, syphilis, HIV, HBV, and HCV

14. Denies history of bleeding diathesis

15. Denies history of seizures (due to reports of seizures with ciprofloxacin)

16. Denies history of cancer, except basal cell carcinoma of the skin > 5 years ago

17. Denies history of drug abuse

18. 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 Human Immunodeficiency Virus (HIV) infection

3. Psychiatric disorders that, in the opinion of the physician, 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. Self-reported chemotherapy within the past year

9. Current steroid use, except for topical application

10. Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine

11. Treatment with medications in the previous month that are contraindicated with cefixime, ceftriaxone or ciprofloxacin and that cannot be withheld for the single doses given in this study

12. Serum creatinine level < 0.7 or > 1.75 mg/dL and deemed clinically significant by the study physician

13. Serum ALT level < LLN or > 105 U/L and deemed clinically significant by the study physician

14. WBC count < 2.5 or > 15.0 x 10^9/L and deemed clinically significant by the study physician

15. Absolute neutrophil count (ANC) < 1.5 or > 7.5 x 10^9/L and deemed clinically significant by the study physician Exception: For African Americans, ANC values as low as 1.3 x 10^9/L will be allowed (25)

16. Hemoglobin level < 12.0 g/dL or above ULN and deemed clinically significant by the study physician

17. Urinalysis: Qualitative protein level > 1+ or RBC count > 10/hpf

Medications not permitted with cefixime or ceftriaxone:

1. Warfarin

2. Probenecid

3. Aspirin

4. Diuretics such as furosemide

5. Aminoglycoside antibiotics

6. Chloramphenicol

Medications not permitted with ciprofloxacin:

1. Tizanidine

2. Theophylline

3. Warfarin

4. Glyburide

5. Cyclosporine

6. Probenecid

7. Phenytoin

8. Methotrexate

9. Antacids, multivitamins, and other dietary supplements containing magnesium, calcium, aluminum, iron or zinc

10. Caffeine-containing medications

11. Sucralfate or didanosine chewable or buffered tablets