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

• ClinicalTrials.gov Identifier: NCT01691612
• Recruitment Status: Completed
• First Posted: September 25, 2012
• Results First Posted: July 3, 2017
• Last Update Posted: July 3, 2017
• Sponsor: Brigham and Women's Hospital
• Information provided by (Responsible Party): Elliot Israel, MD, Brigham and Women's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Biological: installation of D. pteronyssinus allergens	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Role of the Isomerase Pin-1 in the Development and Treatment of Asthma
• Study Start Date: March 2013
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

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 Name: D. pteronyssinus allergens exposure

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the Percentage of Total White Blood Cell That Were Eosinophils at 48 Hours [ Time Frame: from baseline to 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 (%)]

Secondary Outcome Measures :

1. Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Lymphocytes at 48 Hours [ Time Frame: from baseline to 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)]
2. Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Macrophages at 48 Hours [ Time Frame: from baseline to 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)]
3. Change From Baseline in the Percentage of Total White Blood Cell That Were Neutrophils at 48 Hours [ Time Frame: from baseline to 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

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Massachusetts

Asthma Research Center

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

• Principal Investigator: Kun P Lu, M.D., PhD; Beth Israel Deaconess Medical Center
• Principal Investigator: Elliot Israel, M.D; Brigham and Womens Hospital

More Information

• Responsible Party: Elliot Israel, MD, Physician, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01691612
• Other Study ID Numbers: 2012P001029
• First Posted: September 25, 2012
• Results First Posted: July 3, 2017
• Last Update Posted: July 3, 2017
• Last Verified: June 2017

Keywords provided by Elliot Israel, MD, Brigham and Women's Hospital:

Role of Pin-1 enzyme in Asthma

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases