- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03840811
Experimental Human Infection With Neisseria Gonorrhoeae
Experimental Human Infection With Isogenic Mutants of Neisseria Gonorrhoeae
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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North Carolina
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Chapel Hill, North Carolina, United States, 27514-4220
- University of North Carolina Health Care - Infectious Diseases
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy man > / = 18 and < 36 years old
- Able and willing to be located easily by providing street address and telephone number (land line and/or cell phone number)
- Willingness to provide written informed consent
- 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
- Able and willing to abstain from all sexual activity until completion of the study and the follow-up test for gonorrhea is negative
- Acceptable medical history by screening evaluation
- No clinically significant abnormalities on physical exam
- Urinalysis: leukocyte esterase, and White Blood Cell (WBC) values within normal limits (WNL)
- CH50 WNL
- Urine negative for chlamydia, gonorrhea, and trichomonas
- Negative Human Immunodeficiency Virus (HIV), syphilis, and Hepatitis C (HCV) test results
- Negative Hepatitis B (HBV) core and surface antibodies or results consistent with immunization (negative HBV core antibody/positive HBV surface antibody)
- Denies history of Sexually Transmitted Infections (STIs) including gonorrhea, chlamydia, syphilis, HIV, HBV, and HCV
- Denies history of bleeding diathesis
- Denies history of seizures (due to reports of seizures with ciprofloxacin)
- Denies history of cancer, except basal cell carcinoma of the skin > 5 years ago
- Denies history of drug abuse
- Denies history of genitourinary surgery
Exclusion Criteria:
- Student or employee under the direct supervision of any of the study investigators
- Any known immunodeficiencies including complement deficiency, antibody deficiency, chronic granulomatous disease or Human Immunodeficiency Virus (HIV) infection
- Psychiatric disorders that, in the opinion of the physician, would interfere with the integrity of the data or volunteer safety
- 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
- Heart murmur or heart disease
- Anatomic abnormality of the urinary tract
- Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days
- Self-reported chemotherapy within the past year
- Current steroid use, except for topical application
- Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine
- 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
- Serum creatinine level < 0.7 or > 1.75 mg/dL and deemed clinically significant by the study physician
- Serum ALT level < LLN or > 105 U/L and deemed clinically significant by the study physician
- WBC count < 2.5 or > 15.0 x 10^9/L and deemed clinically significant by the study physician
- 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)
- Hemoglobin level < 12.0 g/dL or above ULN and deemed clinically significant by the study physician
- Urinalysis: Qualitative protein level > 1+ or RBC count > 10/hpf
Medications not permitted with cefixime or ceftriaxone:
- Warfarin
- Probenecid
- Aspirin
- Diuretics such as furosemide
- Aminoglycoside antibiotics
- Chloramphenicol
Medications not permitted with ciprofloxacin:
- Tizanidine
- Theophylline
- Warfarin
- Glyburide
- Cyclosporine
- Probenecid
- Phenytoin
- Methotrexate
- Antacids, multivitamins, and other dietary supplements containing magnesium, calcium, aluminum, iron or zinc
- Caffeine-containing medications
- Sucralfate or didanosine chewable or buffered tablets
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1
Subjects (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain
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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
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Experimental: Group 2
Subjects (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain.
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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.
|
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
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Competitive Index of the Mutant Compared to Wild Type Proportion of Organisms With the Predicted Competitive Advantage Recovered From Urine and/or Urethral Swab Specimens From Infected Participants
Time Frame: Baseline and the day of treatment, any day between Day 2 and Day 6
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The competitive index (CI) is defined by the ratio of colony forming units (cfu) of the two strains recovered from urine cultures on the day of treatment (output) compared to the ratio of strains in the inoculum (input): CI = mutant cfu(output)/wild-type cfu(output) ÷ mutant cfu(input)/wild-type cfu(input). The CI is used to assess whether the fitness of a given mutant is different than that of wild-type, and CI as a ratio is compared to 1. If it's not significantly different than 1, then no significant difference in the fitness was observed. Mutant or wild-type cfu values of 0 were replaced by 1 in the calculation of competitive index. The assessment was performed in the MtrD trial mixed group. |
Baseline and the day of treatment, any day between Day 2 and Day 6
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Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture Among Infections Initiated With Individual N. Gonorrhoeae Strains in Non-competitive Infections
Time Frame: day of infection, any day between Day 2 and Day 6
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Infection is defined by a positive urine or urethral swab culture.
The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial by group among participants with non-competitive infections.
Participants could become infected and received treatment any day before or on day 6.
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day of infection, any day between Day 2 and Day 6
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Proportion of Participants That Become Infected as Defined by a Positive Urine or Urethral Swab Culture for Infections Initiated With Mixed Inocula
Time Frame: day of infection, any day between Day 2 and Day 6
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Infection is defined by a positive urine or urethral swab culture.
The proportion of infected participants by Day 6 with N. gonorrhoeae was assessed in each trial among participants with infections initiated with mixed inocula.
Participants could become infected and received treatment any day before or on day 6.
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day of infection, any day between Day 2 and Day 6
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Time From Inoculation to Treatment Among Infected Participants by Day 6, by Strain, in Non-competitive Infections
Time Frame: Day 2 through the day of treatment, up to Day 6
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The median time from inoculation to antibiotic treatment were calculated for each group.
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Day 2 through the day of treatment, up to Day 6
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Proportion of Participants With Occurrence of Bacteriuria in Non-competitive Infections, by Strain
Time Frame: Day of occurrence, any day between Day 2 and Day 6
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Bacteriuria is defined as Log10 cfu N. gonorrhoeae/mL urine sediment.
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Day of occurrence, any day between Day 2 and Day 6
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Proportion of Participants With Occurrence of Signs and Symptoms of Urethritis Attributable to Gonococcal Infection in Non-competitive Infections, by Strain
Time Frame: Day of occurrence, any day between Day 2 and Day 6
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Participants with any subjective symptoms or objective signs (observed urethral discharge) during period 01 (post-inoculation and before treatment which can occur on or before day 6) from the Solicited Events Form were captured.
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Day of occurrence, any day between Day 2 and Day 6
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Proportion of Participants With Occurrence of Urethritis in Non-competitive Infections
Time Frame: Day of occurrence, any day between Day 2 and Day 6
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Urethritis is defined as >= 5.8 Log10 WBC/mL urine sediment.
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Day of occurrence, any day between Day 2 and Day 6
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Sexually Transmitted Diseases
- Disease Attributes
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Neisseriaceae Infections
- Sexually Transmitted Diseases, Bacterial
- Infections
- Communicable Diseases
- Gonorrhea
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors
- Ceftriaxone
- Ciprofloxacin
- Cefixime
Other Study ID Numbers
- 09-0106
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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