Study of Dust Mite Inhalation in Humans
Condition: Mild Asthma; Allergy
MeSH terms: Hypersensitivity
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research study is to learn more about the effect of inhaled dust mite
      allergen extract on airway responses in allergic individuals with mild asthma. Information
      learned from this study will be used to identify a safe dose range of D Farinae extract for
      use in inhalation challenge studies. This study will also help determine how inhalation of
      the allergen affects mucociliary clearance (MCC) which is a measure of how quickly mucus
      clears from the airway.
    

Detailed description: 
      This will be a non-blinded study of the effect of inhaled house dust mite (D Farinae)
      allergen extract on airway responses, with the principal endpoint being a decrease in FEV1 of
      15% within 10 minutes after inhalation of one of a sequence of doses of allergen compared
      with measurements obtained immediately prior to challenge. These doses will be delivered as 5
      inhalations of allergen at concentrations of 0.25, 0.50, 1.0, 2.0, 4.0, 8.0, 16, 32, 64, 125,
      250, 500, 1000, and 2000 AU/mL. Allergen challenge often induces an immediate and late phase
      decrease in lung function. The immediate phase that occurs within 10 minutes, often self
      resolves and is associated with release of histamine from airway mast cells, while the late
      phase response often occurs 2 to 8 hours later and is associated with increased airway
      inflammation.

      During the subject's baseline visit occurring at least 2 days prior to allergen challenge, we
      will measure mucociliary clearance (MCC) of inhaled, radiolabeled particles by gamma
      scintigraphy. The subject will return 24 hours later for a follow-up scan and a sputum sample
      will also be collected. At 4 hours post allergen challenge, we will again measure MCC as an
      exploratory endpoint. It is expected that mucociliary clearance will be depressed as part of
      a late phase reaction to allergen challenge. Twenty-four hours after allergen challenge,
      induced sputum will be obtained and compared with the sputum sample obtained at the baseline
      visit. Exploratory endpoints of interest from examination of induced sputum will also be
      collected after inhaled allergen challenge.

      Observation Schedule (details regarding study procedures follow below):

      Baseline visit

        1. Consent will be obtained

        2. Review of subject's medical history and current medications

        3. Vital sign measurements (temperature, pulse, respiratory rate, blood pressure), oxygen
           saturation, and symptom scoring

        4. Urine pregnancy test for women of child bearing potential

        5. Spirometry

        6. Physical exam of the ears, nose, throat and chest

        7. Xenon equilibrium gas scan

        8. Mucociliary clearance procedure (MCC)

      24 hours post baseline visit

        1. Review any change in medical status over prior 24 hours

        2. Vital signs, oxygen saturation and symptom score

        3. Follow up MCC scan

        4. Sputum induction

      Post Challenge Observations/Reporting Subjects will be contacted for phone call follow-up 24
      hours after sputum induction (see accompanying phone script)

      24-48 hours prior to challenge visit (at least 2 days after the baseline visit)

        1. Review any change in medical status since last visit

        2. Vital signs, oxygen saturation, and symptom score

        3. Spirometry

        4. Physical exam of the ears, nose, throat and chest

      Allergen challenge day

        1. Review any change in medical status since last visit

        2. Vital signs, oxygen saturation, and symptom score

        3. Urine pregnancy test

        4. Spirometry

        5. If above measures are acceptable, allergen challenge will be performed as described

        6. Post-challenge monitoring at intervals indicated on study worksheets

        7. Four hours post challenge, subject will have MCC evaluated

        8. Overnight stay in the UNC General Clinical Research Center (GCRC) Subjects will be
           instructed to perform either spirometry with a personal spirometer or peak flow
           assessments on an every other hourly basis until at least 9 pm, and up to 11 pm if the
           subject is awake.

      24 hours post challenge

        1. Subject is discharged from GCRC, and accompanied by a study staff member, proceeds
           directly to CEMALB.

        2. Vital signs, oxygen saturation, and symptom score

        3. Spirometry

        4. Follow-up MCC scan

        5. Sputum induction

      Post Challenge Observations/Reporting

        1. Subjects will be contacted for phone call follow-up 24 hours after post-challenge sputum
           induction (see accompanying phone script)

        2. Each volunteer will be given a symptom scoring sheet for each day up to 96 hours (4
           days) after challenge (see accompanying symptom scoring sheet)

      Study discontinuation visit within 10 days of the final challenge dose:

        1. Vital signs, oxygen saturation, and symptom score

        2. Spirometry

        3. If any findings are abnormal, medical evaluation as directed by the study physician will
           be undertaken
    

Intervention name(s): inhaled allergen challenge
Intervention type(s): Biological
Intervention description(s): Subjects will inhale gradually increasing concentrations of Dermatophagoides farinae until a 15% drop in FEV1 is noted
Other intervention name(s): dust mites
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: asthma; allergy