Clinical trial NCT01691612: Role of the Isomerase Pin-1 in the Development and Treatment of Asthma
Official title: Role of the Isomerase Pin-1 in the Development and Treatment of Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Role of Pin-1 enzyme in Asthma
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2012-09-25
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.

Detailed description: The investigators will test their hypothesis that Pin1 regulates TLR/IL-1R signaling pathways in asthma by examining Pin1 and related pathway activation in BAL-derived eosinophils after house dust mite allergen challenge. The investigators will perform segmental allergen challenge. BAL and lung biopsy of the allergen-challenged segments will be performed 48 hr later and activation of Pin1 and related pathways will be examined.

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.

Primary outcomes:
measure: Change From Baseline in the Percentage of Total White Blood Cell That Were Eosinophils at 48 Hours
timeFrame: from baseline to 48 hours
Secondary outcomes:
measure: Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Lymphocytes at 48 Hours
timeFrame: from baseline to 48 hours
measure: Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Macrophages at 48 Hours
timeFrame: from baseline to 48 hours
measure: Change From Baseline in the Percentage of Total White Blood Cell That Were Neutrophils at 48 Hours
timeFrame: from baseline to 48 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: Asthma Research Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Kun P Lu, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Womens Hospital
name: Elliot Israel, M.D
role: PRINCIPAL_INVESTIGATOR
References: