This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Elliot Israel, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01691612
First received: September 7, 2012
Last updated: June 6, 2017
Last verified: June 2017
  Purpose
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 Intervention Phase
Asthma Biological: installation of D. pteronyssinus allergens Phase 2

Study Type: Interventional
Study Design: 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

Further study details as provided by Elliot Israel, MD, Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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:
  • 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)]

  • 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)]

  • 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


Enrollment: 14
Study Start Date: March 2013
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691612

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     History of Changes
Other Study ID Numbers: 2012P001029
Study First Received: September 7, 2012
Results First Received: March 6, 2017
Last Updated: June 6, 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

ClinicalTrials.gov processed this record on September 21, 2017