Effect of a 10,000 EU Dose of Endotoxin in Allergic and Mildly Asthmatic Adults
Condition: Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Asthma
MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Rhinitis, Allergic, Perennial
Study type: Interventional
Phase: Phase 1

Summary: 
      The purposes of this pilot safety study are to identify a dose of inhaled Clinical Center
      Reference Endotoxin (CCRE) that is well tolerated by allergic subjects that induces
      measurable increases in neutrophil content of induced sputum that can be employed to screen
      large populations for susceptibility to the inflammatory effect of inhaled endotoxin.
    

Detailed description: 
      Twenty-four or forty-eight hours (study day 1) prior to the inhalation challenge, subjects
      will undergo a physical examination of the ears, nose, throat and chest and will have an
      assessment of vital signs (temperature, pulse, respiratory rate, blood pressure), oxygen
      saturation, symptom score assessment and undergo spirometry to rule out acute illness prior
      to challenge. All female volunteers will undergo a urine pregnancy test. A similar
      examination will take place immediately prior to inhalation challenge with 10,000 EU of CCRE,
      as well as 30, 60, 120, 180, 240, 300 and 360 minutes and 24 hours after challenge (with the
      exception of a pregnancy test which will only be administered prior to sputum induction on
      study day 1). Induced sputum will be 24 to 48 hours prior to challenge, and again six hours
      after challenge on Study day 2. Sputum will be analyzed for PMN content, CD14 expression on
      airway macrophages and monocytes, soluble CD14 levels, cytokine levels in sputum and products
      of inflammatory cells (eosinophil, cationic protein, myeloperoxidase). Blood will be
      collected for a CBC and differential when the pre- challenge induced sputum is obtained and
      again 6 hours after challenge. Subjects will then be escorted to the GCRC for overnight
      admission. While on the GCRC, vital signs will be obtained every 2 hours till bedtime, then
      once a shift. Spirometry will not be obtained while the subject is in the GCRC, however the
      subject will be given symptom scoring cards. The next morning (study day 3) subjects will be
      discharged and escorted to the CEMALB for a final set of vital signs, spirometry, symptom
      scoring, and an examination by a study physician.

      Each volunteer will be given a symptom scoring sheet for each day up to 96 hours (4 days)
      after challenge.

      Each sheet will include the name and phone number of the study coordinator and study MD.
      Sample home symptom scoring sheets and instructions are included with this protocol.

      Between 48 and 96 hours after challenge, each volunteer will be called to determine their
      status, inquiring about symptoms, symptom scoring, and need for medication and/or physician
      visits.

      Between 7 and 10 days of the challenge dose, each subject will be asked to return for a study
      discontinuation visit. At that time temperature, pulse, systolic and diastolic BP,
      respiratory rate, FVC and FEV1 and SpO2 (oxygen saturation), and symptoms scores will be
      assessed and, if abnormal, medical evaluation as directed by the study physician will be
      undertaken.
    

Intervention name(s): Clinical Center Reference Endotoxin (CCRE)
Intervention type(s): Biological
Intervention description(s): Inhalation of 10,000 EU CCRE
Other intervention name(s): LPS; endotoxin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: CCRE; endotoxin; LPS; asthma; allergies; allergic rhinitis