Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Experimental Human Infection With Neisseria Gonorrhoeae

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03840811
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Condition or disease Intervention/treatment Phase
Gonococcal Infection Drug: Cefixime Drug: Ceftriaxone Drug: Ciprofloxacin Biological: Neisseria gonorrhoeae strain FA1090 A26 Biological: Neisseria gonorrhoeae strain FA7537 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Experimental Human Infection With Isogenic Mutants of Neisseria Gonorrhoeae
Actual Study Start Date : April 23, 2017
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Gonorrhea
Drug Information available for: Neisseria

Arm Intervention/treatment
Experimental: Group 1
Subjects (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain
Drug: Cefixime
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.

Drug: Ceftriaxone
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.

Drug: Ciprofloxacin
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

Biological: Neisseria gonorrhoeae strain FA7537
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

Experimental: Group 2
Subjects (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
Drug: Cefixime
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.

Drug: Ceftriaxone
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.

Drug: Ciprofloxacin
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

Biological: Neisseria gonorrhoeae strain FA1090 A26
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.

Experimental: Group 3
Subjects (n= up to 16) will receive a bacterial inoculum containing a mixture of equivalent numbers the isogenic mutant and WT strain
Drug: Cefixime
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.

Drug: Ceftriaxone
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.

Drug: Ciprofloxacin
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

Biological: Neisseria gonorrhoeae strain FA1090 A26
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.

Biological: Neisseria gonorrhoeae strain FA7537
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




Primary Outcome Measures :
  1. The competitive index (CI) of the mutant compared to WT proportion of organisms with the predicted competitive advantage recovered from urine and/or urethral swab specimens from among individual infected subjects [ Time Frame: Day 2 through Day 6 ]
  2. The proportion of subjects that become infected as defined by a positive urine or urethral swab culture among infections initiated with individual N. gonorrhoeae strains [ Time Frame: Day 6 ]
  3. The proportion of subjects that become infected as defined by a positive urine or urethral swab culture for infections initiated with mixed inocula [ Time Frame: Day 6 ]

Secondary Outcome Measures :
  1. Median time from isogenic mutant N. gonorrhoeae strain inoculation to treatment among infected subjects [ Time Frame: Day 6 ]
  2. Median time from wild-type (WT) N. gonorrhoeae strain inoculation to treatment among infected subjects [ Time Frame: Day 6 ]
  3. The occurrence of bacteriuria (Log10 cfu N. gonorrhoeae/mL urine sediment) [ Time Frame: Day 2 through Day 6 ]
  4. The occurrence of signs and symptoms of urethritis attributable to gonococcal infection [ Time Frame: Day 6 ]
  5. The occurrence of urethritis (> 5.8 Log10 WBC/mL urine sediment) [ Time Frame: Day 2 through Day 6 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 36 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03840811


Contacts
Layout table for location contacts
Contact: Marcia M Hobbs 19198436893 mmhobbs@med.unc.edu

Locations
Layout table for location information
United States, North Carolina
University of North Carolina Health Care - Infectious Diseases Recruiting
Chapel Hill, North Carolina, United States, 27514-4220
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03840811     History of Changes
Other Study ID Numbers: 09-0106
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: March 19, 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
ceftriaxone
challenge
ciprofloxacin
males
Neisseria gonorrhoeae
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Gonorrhea
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Sexually Transmitted Diseases, Bacterial
Sexually Transmitted Diseases
Genital Diseases, Male
Genital Diseases, Female
Ciprofloxacin
Ceftriaxone
Cefixime
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors