Role of the Isomerase Pin-1 in the Development and Treatment of Asthma

NCT ID: NCT01691612

Last Updated: 2017-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2015-05-31

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.

Conditions

Asthma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

D. pteronyssinus allergens

Single arm study exploring the role of Pin-1 enzyme in development of Asthma. Bronchoscopy before and 48 hours after installation of D. pteronyssinus allergens into the lung segments

Group Type: EXPERIMENTAL

installation of D. pteronyssinus allergens

Intervention Type: BIOLOGICAL

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

Interventions

installation of D. pteronyssinus allergens

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

Intervention Type: BIOLOGICAL

Other Intervention Names

D. pteronyssinus allergens exposure

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Elliot Israel, MD

Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kun P Lu, M.D., PhD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Elliot Israel, M.D

Role: PRINCIPAL_INVESTIGATOR

Brigham and Womens Hospital

Locations

Asthma Research Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2012P001029

Identifier Type: -

Identifier Source: org_study_id