Nontypeable H. Influenzae in Healthy Adults
Condition: Haemophilus Influenzae (NTHI)
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

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
    

Intervention name(s): NTHi Strain 2019
Intervention type(s): Biological
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Keywords: nontypeable Haemophilus influenzae, NTHi