Role of the Isomerase Pin-1 in the Development and Treatment of Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: installation of D. pteronyssinus allergens
Intervention description: We will perform bronchoscopy and segmental allergen challenges. Subjects will undergo bronchoscopy with segmental installation of 5 ml of D. pteronyssinus (DerP). BAL and lung biopsy of the allergen-challenged segments will be performed 48 hr later
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Role of Pin-1 enzyme in Asthma

Summary:

      Pin1 is activated in asthmatic airways, increasing cytokine mRNA stability and eosinophil
      survival. This study is designed to test whether the Pin1 enzyme regulates TLR/IL-1R signal
      pathways in multiple cells in asthma.
    

Eligibility criteria:

        Inclusion criteria:

          -  Subjects 18-55 years of age, diagnosed with asthma for at least 1 year;

          -  And FEV1 > 70% predicted on only short acting beta agonists e.g albuterol

          -  And methacholine PC20 < 8 mg/ml

          -  Positive skin prick test to Dermatophagoides pteronyssinus(DerP)

          -  No prior history of intubation for asthma

          -  No use of inhaled corticosteroids for 1 month prior to entry

        Exclusion criteria:

          -  Current smoking or smoking history of greater than 10 pack-years

          -  Any other clinically important comorbidity determined by the principal investigator to
             affect subject safety, including uncontrolled diabetes, uncontrolled coronary artery
             disease, acute or chronic renal failure, and uncontrolled hypertension that would
             increase the risk of significant adverse events during bronchoscopy,

          -  Worsening of asthma symptoms requiring treatment with steroids within 4 weeks of
             screening

          -  Respiratory infection within four weeks

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant or who are currently pregnant or lactating.

        Unless they:

          -  Are women whose career, lifestyle, or sexual orientation precludes intercourse with a
             male partner

          -  Are women whose partners have been sterilized by vasectomy or other means

          -  Use one acceptable birth control method. Adequate barrier methods of contraception
             include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal),
             sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent
             that includes an estrogen and/or a progestational agent.

          -  Pre-existing lung disease other than asthma

          -  History of coagulation disorders or abnormal PT/PTT testing at screening

          -  History of immunodeficiency diseases, including HIV

          -  A disability that may prevent the patient from completing all study requirements

          -  Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever is longer

          -  History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years, regardless of whether
             there is evidence of local recurrence or metastases.

          -  Diagnosis of Hepatitis B or C.

          -  History of alcohol abuse (as determined by the principal investigator) within 6 months
             of screening.

          -  History of illicit drug abuse (as determined by the principal investigator) within 6
             months of screening.