Role of the Isomerase Pin-1 in the Development and Treatment of Asthma (Pin1)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: installation of D. pteronyssinus allergens

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Asthma Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: 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; Other Names: D. pteronyssinus allergens exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Percentage of Total White Blood Cell That Were Eosinophils at 48 Hours	Measure Pin1 activity in BAL-derived eosinophils after House Dust Mite (HDM) allergen challenge: Eosinophils post-challenge change from pre-challenge is reported: absolute change = [eosinophils post (%) - eosinophils pre (%)]	from baseline to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Lymphocytes at 48 Hours	Percent change in percentage of total white blood cell that were lymphocytes is measured from pre-challenge to post-challenge as: [100% * ((Post-Pre)/Pre)]	from baseline to 48 hours
Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Macrophages at 48 Hours	Percent change in percentage of total white blood cell that were macrophages is measured from pre-challenge to post-challenge as: [100% * ((Post-Pre)/Pre)]	from baseline to 48 hours
Change From Baseline in the Percentage of Total White Blood Cell That Were Neutrophils at 48 Hours	Neutrophils have some zero values pre-challenge, so absolute change is reported instead of percent change: post-pre from baseline to 48 hours	from baseline to 48 hours

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Kun P Lu, M.D., PhD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: September 7, 2012
• First Submitted That Met QC Criteria: September 20, 2012
• First Posted (Estimate): September 25, 2012

Study Record Updates

• Last Update Posted (Actual): July 3, 2017
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Role of Pin-1 enzyme in Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 2012P001029