Gonococcal InfectionPhase 1NCT04870138
Experimental Human Infection With Neisseria Gonorrhoeae (LptA Trial)
A Phase 1 study testing Azithromycin, Ceftriaxone and Ciprofloxacin in people with Gonococcal Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Gonococcal Infection
- What is being tested?
- Azithromycin, Ceftriaxone and Ciprofloxacin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2013to 28 Apr 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy man between the ages of 18 and 35 years.
- 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 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.
- Able and willing to abstain from masturbation during the 6-day stay in the CTRC.
- Able and willing to abstain from all sexual activity during the course of the study.
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- Acceptable medical history by screening evaluation.
- Standard physical exam within normal limits (WNL).
- Serum creatinine WNL.
- Serum alanine transaminase (ALT) WNL.
- White blood cell (WBC), polymorphonuclear cell (PMN) and hemoglobin values WNL.
- Normal urinalysis.
- Total Complement (CH50) WNL.
- Urine negative for chlamydia, gonorrhea, trichomonas and mycoplasma.
- Negative 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 STIs including syphilis and hepatitis B \& C.
- 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 more than 5 years ago.
- Denies history of drug abuse.
- Denies history of psychiatric disorders, except depression controlled by medication.
- Denies history of genitourinary surgery.
Who cannot join
- 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 HIV infection.
- Psychiatric disorders that 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.
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- Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days.
- Chemotherapy within the past year.
- Current steroid use, except for topical application.
- Allergy to penicillin, ceftriaxone or ciprofloxacin or to lidocaine.
- Treatment with medications that are contraindicated with ciprofloxacin or ceftriaxone and that cannot be withheld for the single doses given in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina Health Care - Infectious Diseases
Chapel Hill, North Carolina, 27514-4220
About this study
Official title: Experimental Human Infection With Isogenic Mutants of Neisseria Gonorrhoeae (LptA Trial)
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.
Read the detailed description
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 hypothesize that key virulence determinants involved in N. gonorrhoeae adherence and resistance to innate immunity are essential for infection in the male urethra. We predict that mutations abolishing expression of these virulence determinants will eliminate or significantly reduce gonococcal infectivity or the ability to induce inflammation in an infected individual, thus identifying potential vaccine candidates. For each mutant to be investigated under this protocol, initial trials will be conducted in which subjects receive a bacterial inoculum containing a mixture of equivalent numbers of two isogenic strains, differing in expression of one or more genes. A competitive advantage for one strain during urethral infection will be manifest by recovery of that strain in a statistically significantly higher proportion of isolates recovered from infected subjects than in the inoculum. Following infections with mixed inocula, infectivity of the mutant in single-strain infections will be compared to that of the wild-type in single-strain infections. In addition, the proportion of infected subjects that develop signs or symptoms of urethritis with mutant and wild- type inocula will be compared. The Mixed FA7527/FA1090 group (n = up to 25 ) will receive a bacterial inoculum containing a mixture of equivalent numbers of the isogenic mutant and WT strains. In single-strain infections, the Mutant FA7527 group (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain, and the Wild-type FA1090 group (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae 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. 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. The study secondary objectives are to: (1) characterize host immune responses to infection by measuring cytokines and other mediators in specimens including serum, peripheral blood lymphocytes and urine obtained from subjects before, during and after experimental gonococcal infection, and (2) characterize bacterial gene expression during experimental infection.
- Conditions
- Gonococcal Infection
- Being tested
- Azithromycin, Ceftriaxone, Ciprofloxacin, Neisseria gonorrhoeae strain FA1090 A26, Neisseria gonorrhoeae strain FA7527
- Keywords
- ceftriaxone, challenge, ciprofloxacin, males, Neisseria gonorrhoeae
- Medical subject headings
- Gonorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Alternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics.
CeftriaxoneDrug
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.
CiprofloxacinDrug
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.
Neisseria gonorrhoeae strain FA1090 A26Biological
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.
Neisseria gonorrhoeae strain FA7527Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| Mixed FA7527/FA1090 | Experimental | Bacterial inoculum containing a mixture of equivalent numbers of the isogenic LptA mutant and wild-type (WT) strain administered once to the anterior urethra. N= up to 25 Receives: Drug: Azithromycin; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090 A26; Biological: Neisseria gonorrhoeae strain FA7527 |
| Mutant FA7527 | Experimental | Bacterial inoculum containing only the isogenic LptA mutant N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8 Receives: Drug: Azithromycin; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA7527 |
| Wild-type FA1090 | Experimental | Bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8 Receives: Drug: Azithromycin; Drug: Ceftriaxone; Drug: Ciprofloxacin; Biological: Neisseria gonorrhoeae strain FA1090 A26 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Participants That Become Infected With Individual N. Gonorrhoeae Strains in Non-competitive Infections
Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. The proportion of infected participants by Day 5 with N. gonorrhoeae was assessed by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 5.
Measured: Day of infection, any day between Day 1 and Day 5
The Proportion of Participants That Become Infected With Mixed Inoculum
Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. Participants could become infected and received treatment any day before or on day 5.
Measured: Day of infection, any day between Day 1 and Day 5
The Proportion of Wild Type (WT) Organisms Recovered From Urine and Urethral Swab Specimens From Individual Subjects Infected With Mixed Inoculum
Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. Participants could become infected and received treatment any day before or on day 5.
Measured: Baseline (Day 0) and the day of infection (any day between Day 1 and Day 5)
Secondary outcomes (24)
EGF Cytokine Levels in Peripheral Blood
EGF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Eotaxin Cytokine Levels in Peripheral Blood
Eotaxin cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
G-CSF Cytokine Levels in Peripheral Blood
G-CSF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Fractalkine Cytokine Levels in Peripheral Blood
Fractalkine Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
GRO Cytokine Levels in Peripheral Blood
GRO Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-1RA Cytokine Levels in Peripheral Blood
IL-1RA Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-8 Cytokine Levels in Peripheral Blood
IL-8 Cytokine levels in peripheral blood collected from subjects were measured at the eligibility testing visit, during experimental infection and at the follow-up visit. Only cytokines detected during experimental infection in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IP-10 Cytokine Levels in Peripheral Blood
IP-10 Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MCP-1 Cytokine Levels in Peripheral Blood
MCP-1 Cytokine levels in peripheral blood collected from subjects were measured at the eligibility testing visit, during experimental infection and at the follow-up visit. Only cytokines detected during experimental infection in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MIP-1Beta Cytokine Levels in Peripheral Blood
MIP-1Beta Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
VEGF Cytokine Levels in Peripheral Blood
VEGF Cytokine levels in peripheral blood collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
EGF Cytokine Levels in Urine
EGF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Eotaxin Cytokine Levels in Urine
Eotaxin Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
G-CSF Cytokine Levels in Urine
G-CSF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Fractalkine Cytokine Levels in Urine
Fractalkine Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
GRO Cytokine Levels in Urine
GRO Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-1RA Cytokine Levels in Urine
IL-1RA Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-8 Cytokine Levels in Urine
IL-8 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IP-10 Cytokine Levels in Urine
IP-10 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MCP-1 Cytokine Levels in Urine
MCP-1 Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MIP-1Beta Cytokine Levels in Urine
MIP-1Beta Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
VEGF Cytokine Levels in Urine
VEGF Cytokine levels in urine collected from subjects were measured at the screening visit, during experimental infection and at the follow-up visit. Only cytokines detected during the treatment visit upon experimental infection or day 5 in > 50% of both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of quantitation are assigned 1/2 the lower limit of quantitation for calculation of mean values; limits of 95% confidence intervals are bounded by 1/2 the lower limit of quantitation and the upper limit of quantitation for each cytokine. Only the cytokines measured in both the urine and peripheral blood samples are included. Cytokine outcome values reported below the limit of detection are excluded.
Measured: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Pattern of Gonococcal Gene Expression in Urine Sediment
RNA-seq is the standard method for measuring bacterial gene expression.
Measured: Day 1 through Day 5
Quantity of Gonococcal Gene Expression in Urine Sediment
RNA-seq is the standard method for measuring bacterial gene expression.
Measured: Day 1 through Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2021
- Study start10 Mar 2013
- Primary completion28 Apr 2015
- Study completion28 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gonococcal InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04870138
- Sponsor's protocol ID
- 09-0106 LptA
- Status last verified
- Sep 2020
- First submitted
- 29 Apr 2021
- Last updated
- 2 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Experimental Human Infection With Isogenic Mutants of Neisseria Gonorrhoeae (LptA Trial)
- ClinicalTrials.gov ID
- NCT04870138
- Acronym / sponsor ID
- 09-0106 LptA
- Conditions
- Gonococcal Infection
- Keywords
- ceftriaxone, challenge, ciprofloxacin, males, Neisseria gonorrhoeae
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 10 Mar 2013 (actual)
- Primary completion
- 28 Apr 2015 (actual)
- Study completion
- 28 Apr 2015 (actual)
- First posted
- 3 May 2021 (actual)
- Results
- Posted 2 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 hypothesize that key virulence determinants involved in N. gonorrhoeae adherence and resistance to innate immunity are essential for infection in the male urethra. We predict that mutations abolishing expression of these virulence determinants will eliminate or significantly reduce gonococcal infectivity or the ability to induce inflammation in an infected individual, thus identifying potential vaccine candidates. For each mutant to be investigated under this protocol, initial trials will be conducted in which subjects receive a bacterial inoculum containing a mixture of equivalent numbers of two isogenic strains, differing in expression of one or more genes. A competitive advantage for one strain during urethral infection will be manifest by recovery of that strain in a statistically significantly higher proportion of isolates recovered from infected subjects than in the inoculum. Following infections with mixed inocula, infectivity of the mutant in single-strain infections will be compared to that of the wild-type in single-strain infections. In addition, the proportion of infected subjects that develop signs or symptoms of urethritis with mutant and wild- type inocula will be compared. The Mixed FA7527/FA1090 group (n = up to 25 ) will receive a bacterial inoculum containing a mixture of equivalent numbers of the isogenic mutant and WT strains. In single-strain infections, the Mutant FA7527 group (n = up to 8) will receive a bacterial inoculum containing only the isogenic mutant N. gonorrhoeae strain, and the Wild-type FA1090 group (n = up to 8) will receive a bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae 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. 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. The study secondary objectives are to: (1) characterize host immune responses to infection by measuring cytokines and other mediators in specimens including serum, peripheral blood lymphocytes and urine obtained from subjects before, during and after experimental gonococcal infection, and (2) characterize bacterial gene expression during experimental infection.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mixed FA7527/FA1090 | Experimental | Drug: Azithromycin, Drug: Ceftriaxone, Drug: Ciprofloxacin, Biological: Neisseria gonorrhoeae strain FA1090 A26, Biological: Neisseria gonorrhoeae strain FA7527Bacterial inoculum containing a mixture of equivalent numbers of the isogenic LptA mutant and wild-type (WT) strain administered once to the anterior urethra. N= up to 25 |
| Mutant FA7527 | Experimental | Drug: Azithromycin, Drug: Ceftriaxone, Drug: Ciprofloxacin, Biological: Neisseria gonorrhoeae strain FA7527Bacterial inoculum containing only the isogenic LptA mutant N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8 |
| Wild-type FA1090 | Experimental | Drug: Azithromycin, Drug: Ceftriaxone, Drug: Ciprofloxacin, Biological: Neisseria gonorrhoeae strain FA1090 A26Bacterial inoculum containing only the wild-type (WT) N. gonorrhoeae strain administered once to the anterior urethra. N= up to 8 |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- Healthy man between the ages of 18 and 35 years.
- 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 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.
- Able and willing to abstain from masturbation during the 6-day stay in the CTRC.
Key exclusion criteria (11 listed)
- 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 HIV infection.
- Psychiatric disorders that 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinAlternative antibiotic treatment failure therapy: Azithromycin 2 g orally in a single dose after treatment failure with both cephalosporin and quinolone antibiotics. | Drug | Mixed FA7527/FA1090, Mutant FA7527, Wild-type FA1090 |
| CeftriaxoneMandatory 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. | Drug | Mixed FA7527/FA1090, Mutant FA7527, Wild-type FA1090 |
| CiprofloxacinMandatory 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. | Drug | Mixed FA7527/FA1090, Mutant FA7527, Wild-type FA1090 |
| Neisseria gonorrhoeae strain FA1090 A260.4 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. | Biological | Mixed FA7527/FA1090, Wild-type FA1090 |
| Neisseria gonorrhoeae strain FA75270.4 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. | Biological | Mixed FA7527/FA1090, Mutant FA7527 |
Primary outcome
The Proportion of Participants That Become Infected With Individual N. Gonorrhoeae Strains in Non-competitive Infections
Time frame: Day of infection, any day between Day 1 and Day 5
Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. The proportion of infected participants by Day 5 with N. gonorrhoeae was assessed by group among participants with non-competitive infections. Participants could become infected and received treatment any day before or on day 5.
The Proportion of Participants That Become Infected With Mixed Inoculum
Time frame: Day of infection, any day between Day 1 and Day 5
Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. Participants could become infected and received treatment any day before or on day 5.
The Proportion of Wild Type (WT) Organisms Recovered From Urine and Urethral Swab Specimens From Individual Subjects Infected With Mixed Inoculum
Time frame: Baseline (Day 0) and the day of infection (any day between Day 1 and Day 5)
Infection defined as reported symptoms of urethritis, including urethral discharge or dysuria, plus presence of gram-negative intracellular diplococci in a urethral swab smear. Participants could become infected and received treatment any day before or on day 5.
24 secondary outcomes
EGF Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Eotaxin Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
G-CSF Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Fractalkine Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
GRO Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-1RA Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-8 Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IP-10 Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MCP-1 Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MIP-1Beta Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
VEGF Cytokine Levels in Peripheral Blood
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
EGF Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Eotaxin Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
G-CSF Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Fractalkine Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
GRO Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-1RA Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IL-8 Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
IP-10 Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MCP-1 Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
MIP-1Beta Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
VEGF Cytokine Levels in Urine
Time frame: Screening Visit (Day -30 to Day -1), Treatment Visit (Day 1 to Day 5), and Follow-Up Visit (3 to 7 days following Treatment Visit)
Pattern of Gonococcal Gene Expression in Urine Sediment
Time frame: Day 1 through Day 5
Quantity of Gonococcal Gene Expression in Urine Sediment
Time frame: Day 1 through Day 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azithromycin, Ceftriaxone and Ciprofloxacin in people with Gonococcal Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Participants That Become Infected With Individual N. Gonorrhoeae Strains in Non-competitive Infections (time frame: Day of infection, any day between Day 1 and Day 5). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2021.