Nontypeable H. Influenzae in Healthy Adults

April 4, 2013 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Phase I/II Single-Site, Randomized and Double-Blinded Trial to Further Characterize the HCD50, HCD90 and Transmissibility of Nontypeable Haemophilus Influenzae in a Human Colonization Model in Healthy Adults

The purpose of this study is to learn more about the safety of Haemophilus (H.) influenzae, its ability to produce adverse reactions and to live in the nose and throat. The nose and throat of healthy adults will be populated with a specific type of H. influenzae Nontypeable Haemophilus influenzae (NTHi) 2019 Streptomycin Resistant (StrR) number 1. Researchers will study whether the germ settles in the nose and throat, whether it causes symptoms after it has been placed in the nose, how long the germs last in the nose and throat, and whether the body tries to produce a permanent defense to the germ. Volunteers will receive a lower dose (3,200 germs) or a higher dose (32,000 germs). Active participation will last about 28 days, including a 3 night hospital stay, additional follow-up visits, followed by a 6 month follow-up phone call. Study procedures will include blood samples, saliva samples, several nose washes and throat swabs.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Haemophilus (H.) influenzae continues to be a major human pathogen causing upper and lower respiratory tract diseases ranging from otitis media and sinusitis to invasive pneumonia. The inoculation by nasal droplets proposed in this trial will introduce the organism into the nasal mucosa, the natural host tissue for H. influenzae colonization. It is hypothesized that this inoculum will elicit the typical nasal colonization seen in healthy individuals. To further develop this colonization model, healthy adults devoid of chronic medical conditions that might predispose the subject to invasive disease, will be enrolled. This study is linked to Division of Microbiology and Infectious Diseases (DMID) protocol 04-022. Final safety and reactogenicity data from DMID 04-022, have been collated. This nasal colonization model evaluated 15 volunteers and determined that the model was safe in these individuals and identified a human colonizing dose (HCD) 50 and HCD 90. However, the confidence intervals for these HCD doses were broad. The goals of this study are to further characterize the safety of this trial and to further refine the HCD 50 and 90 doses. This study is a single-site, randomized and blinded study designed to develop a colonization model for Nontypeable Haemophilus influenzae (NTHi). Ten healthy young adults ages 18-54 will be enrolled and inoculated with either 3,200 colony forming units (CFU) or 32,000 CFU of NTHi strain 2019 Streptomycin Resistant (StrR) number 1 and will be followed with nasal wash and throat swabs to determine whether colonization with NTHi 2019 StrR number 1 develops. Subjects that meet enrollment criteria will be admitted to the inpatient clinical research unit to a private room to stay from day 0 thru the morning of day 3 (visits 2-5) to evaluate for reactogenicity after nasal inoculation. During the hospital stay, subjects will remain in respiratory isolation. On day 0, five volunteers will be inoculated at the lower dose, 3,200 CFU, and five will be inoculated with higher dose, 32,000 CFU. After inoculation, primary volunteers will be followed daily for 6 days (visits 2-8, days 0-6) for clinical assessment and culture. Days 4-6, inoculated volunteers will return on a daily basis for a review of reactogenicity parameters, solicitation of adverse events (AEs), a targeted physical exam and pharyngeal swab and nasal wash specimens will be obtained. On day 6, visit 8, after pharyngeal swab and nasal wash samples have been collected and women of child bearing potential have had a urine pregnancy test performed, inoculated volunteers will receive 3 days of levofloxacin to eradicate any potential colonizing study organisms. Participants will return on days 14 and 28 to assess for any AEs, a targeted physical exam will be performed and pharyngeal swab, nasal wash, blood and saliva will be collected. A telephone visit will be performed 6 months after inoculation. A substudy will be performed to evaluate whether casual contact can serve as a mechanism for transmission of NTHi 2019 StrR number 1 from a colonized individual to a casual contact. Three and up to 10 subjects will be recruited to this substudy. They will spend 3-5 hours per day for 6 days with the subject in nonintimate contact and will be followed with nasal wash and throat swabs to determine whether colonization with NTHi 2019 StrR develops. The primary objective of the study is to evaluate the safety and reactogenicity of NTHi Strain 2019 StrR number 1 administered by nasal drop inoculation. The secondary objectives are to: evaluate the frequency and duration of colonization with NTHi strain 2019 StrR number 1 and to establish a human colonizing dose 5

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242-1009
        • University of Iowa - Infectious Disease Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Inclusion Criteria for Inoculated Volunteers:

  • Healthy 18-54 years old (male or female) with no chronic medical conditions with the exception of well-controlled hypertension
  • Availability for study visits over the next 1 month
  • Normal hemoglobin, white blood cell count, creatinine, alanine aminotransferase (ALT), platelet count
  • Signed informed consent form
  • In good health as determined by medical history and physical exam on the screening evaluation [including heart rate 55-100 beats per minute (bpm); blood pressure: systolic 90-140 mm Hg and diastolic 50-90 mm Hg]. If the subject is a well trained athlete by the judgment of the Principal Investigator (PI), heart rate of 40-100 bpm is acceptable.
  • Negative urine pregnancy test for women of childbearing potential
  • If the subject is female and of childbearing potential, she agrees to use acceptable contraception and not become pregnant for the duration of the study. (Acceptable contraception includes abstinence, implants, injectables, combined oral contraceptives, effective intrauterine devices, or a vasectomized partner)
  • Negative human immunodeficiency virus (HIV) enzyme linked immunosorbent assay (ELISA) for HIV 1 and 2 or indeterminate Western blot or other assay confirming that the serostatus does not reflect HIV infection, negative hepatitis C and hepatitis B serology or other assay confirming that the serostatus does not reflect active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection
  • Negative urine protein and glucose by dipstick
  • Subjects must be willing to be housed in the clinical research unit for the first 3 nights of the inoculation period.

Inclusion Criteria for Transmissibility Substudy:

  • Healthy 18-54 years old (male or female) with no chronic medical conditions with the exception of well-controlled hypertension
  • Normal hemoglobin, white blood cell count, creatinine, ALT, platelet count
  • Negative HIV ELISA for HIV 1 and 2 or indeterminate Western blot or other assay confirming that the serostatus does not reflect HIV infection, negative hepatitis C and hepatitis B serology or other assay confirming that the serostatus does not reflect active HCV or HBV infection
  • Negative urine protein and glucose by dipstick
  • Availability for study visits over the next 1 month
  • Signed informed consent form
  • In good health as determined by medical history and physical exam on the screening evaluation (including heart rate 55-100 bpm; blood pressure: systolic 90-140 mm Hg and diastolic 50-90 mm Hg). If the subject is a well trained athlete by the judgment of the PI, heart rate of 40-100 bpm is acceptable.
  • Negative urine pregnancy test for women of childbearing potential
  • If the subject is female and of childbearing potential, she agrees to use acceptable contraception and not become pregnant for the duration of the study. (Acceptable contraception includes abstinence, implants, injectables, combined oral contraceptives, effective intrauterine devices, or a vasectomized partner)
  • Subjects must be willing to spend 3-5 hours per day for 6 days in nonintimate contact with their paired inoculated contact.

Exclusion Criteria:

Exclusion Criteria for Inoculated Volunteers:

  • Acute illness within the week prior to inoculation
  • Acute febrile illness (oral temperature greater than or equal to 100.4 degrees Fahrenheit) on the day of inoculation
  • Allergic rhinitis requiring therapy in the past year
  • Treatment for sinusitis, otitis, chronic bronchitis, pneumonia, bronchospasm or asthma in the past 5 years
  • Abnormal gag reflex
  • Active drug or alcohol abuse
  • Smoking tobacco within the past year
  • Average ingestion of more than one alcoholic beverage per day for women or two alcoholic beverages per day for men
  • Splenectomy or disease that results in functional asplenism such as sickle cell diseases
  • History of malignancy
  • Human immunodeficiency virus (HIV) 1 or 2 infection, autoimmune, immunocompromising diseases, diabetes, or chronic renal, hepatic, pulmonary or cardiovascular diseases
  • Uncontrolled depression or depression involving institutionalization, history of schizophrenia or psychosis, history of suicide attempt
  • Pregnant or lactating woman
  • Use of steroids (systemic, inhaled or intranasal) or other medications that can cause immunosuppression within the past 28 days
  • American Indian, Native Alaskan or Native Australian heritage (aboriginal)
  • Allergy to penicillin, macrolide, cephalosporin or fluoroquinolone antibiotics
  • Use of any antibiotic within the past month
  • Close contact (household, work or school contact/sexual contacts with, or frequent and/or prolonged exposure to) with persons less than 5 or greater than 55 years old; chronic smokers, Native Americans or other native populations outlined above, or those having HIV infection, cancer, chronic diseases or other illness causing immunosuppression; or having asthma or chronic lung disease. Specifically, child care and health care workers are excluded
  • Use of experimental agents or devices within 30 days prior to study or anticipated use of experimental agents or devices within the 6 months of follow up for this study.
  • Receipt of blood products or immunoglobulin in the past 6 months
  • Any condition that, in the opinion of the investigator, might interfere with study objectives
  • Prior participation in nontypeable Haemophilus influenzae colonization studies

Exclusion Criteria for Transmissibility Substudy:

  • Acute illness or fever (oral temperature greater than or equal to 100.4 degrees Fahrenheit) within the week prior to inoculation for their paired inoculated contact
  • Allergic rhinitis requiring therapy in the past year
  • Treatment for sinusitis, otitis, chronic bronchitis, pneumonia, bronchospasm or asthma in the past 5 years
  • Abnormal gag reflex
  • Active drug or alcohol abuse
  • Smoking tobacco within the past year
  • Average ingestion of more than one alcoholic beverage per day for women or two alcoholic beverages per day for men
  • Splenectomy or disease that results in functional asplenism such as sickle cell diseases
  • History of malignancy
  • HIV 1 or 2 infection, autoimmune, immunocompromising diseases, diabetes, or chronic renal, hepatic, pulmonary or cardiovascular diseases
  • Uncontrolled depression or depression involving institutionalization, history of schizophrenia or psychosis, history of suicide attempt
  • Pregnant or lactating woman
  • Use of steroids (systemic, inhaled or intranasal) or other medications that can cause immunosuppression within the past 28 days
  • American Indian, Native Alaskan or Native Australian heritage (aboriginal)
  • Allergy to penicillin, macrolide, cephalosporin or fluoroquinolone antibiotics
  • Use of any antibiotic within the past month
  • Close contact (household contact/sexual contact with, or frequent and/or prolonged exposure to) with persons less than 5 or greater than 55 years old; chronic smokers, Native Americans or other native populations outlined above, or those having HIV infection, cancer, chronic diseases or other illness causing immunosuppression; or having asthma or chronic lung disease
  • Use of experimental agents or devices within 30 days prior to study or anticipated use of experimental agents or devices within the 6 months of follow up for this study
  • Any condition that, in the opinion of the investigator, might interfere with study objectives
  • Prior participation in nontypeable Haemophilus influenzae colonization studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Low Dose: 3,200 CFU
5 subjects inoculated with 3,200 colony forming units (CFU).
Biological: NTHi Strain 2019
Nontypeable Haemophilus influenzae (NTHi) strain 2019 StrR Number 1 is an antibiotic susceptible clinical strain that has a point mutation in the rRNA that renders the isolate resistant to streptomycin. This agent will be introduced by nasal droplets.
Experimental: High Dose: 32,000 CFU
5 subjects inoculated with 32,000 colony forming units (CFU).
Biological: NTHi Strain 2019
Nontypeable Haemophilus influenzae (NTHi) strain 2019 StrR Number 1 is an antibiotic susceptible clinical strain that has a point mutation in the rRNA that renders the isolate resistant to streptomycin. This agent will be introduced by nasal droplets.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Subjects evaluated for reactogenicity using a standardized illness assessment form. Information on additional unexpected adverse events, new medications and any non-routine medical visits will be assessed.
Time Frame: From day 0 to 28 and at 6 months.
From day 0 to 28 and at 6 months.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Frequency and duration of colonization with this bacterium in primary subjects. Nasal wash and pharyngeal swab specimens will be obtained for culture of NTHi 2019 StrR number 1.
Time Frame: Days 0, 3, 4, 5, 6, 14, and 28.
Days 0, 3, 4, 5, 6, 14, and 28.
Transmission of NTHi 2019 StrR number 1 to close contacts evaluated.
Time Frame: Days 0, 3, 6, 10, 14, and 28.
Days 0, 3, 6, 10, 14, and 28.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 18, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 20, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 11, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 07-0091
  • H flu Extension

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings