Role of the Isomerase Pin-1 in the Development and Treatment of Asthma (Pin1)
Primary Purpose
Asthma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
installation of D. pteronyssinus allergens
Sponsored by
About this trial
This is an interventional other trial for Asthma focused on measuring Role of Pin-1 enzyme in Asthma
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.
Sites / Locations
- Asthma Research Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
D. pteronyssinus allergens
Arm Description
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
Outcomes
Primary Outcome Measures
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 (%)]
Secondary Outcome Measures
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)]
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)]
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
Full Information
NCT ID
NCT01691612
First Posted
September 7, 2012
Last Updated
June 6, 2017
Sponsor
Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01691612
Brief Title
Role of the Isomerase Pin-1 in the Development and Treatment of Asthma
Acronym
Pin1
Official Title
Role of the Isomerase Pin-1 in the Development and Treatment of Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Role of Pin-1 enzyme in Asthma
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
D. pteronyssinus allergens
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
installation of D. pteronyssinus allergens
Other Intervention Name(s)
D. pteronyssinus allergens exposure
Intervention Description
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
Primary Outcome Measure Information:
Title
Change From Baseline in the Percentage of Total White Blood Cell That Were Eosinophils at 48 Hours
Description
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 (%)]
Time Frame
from baseline to 48 hours
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Lymphocytes at 48 Hours
Description
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)]
Time Frame
from baseline to 48 hours
Title
Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Macrophages at 48 Hours
Description
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)]
Time Frame
from baseline to 48 hours
Title
Change From Baseline in the Percentage of Total White Blood Cell That Were Neutrophils at 48 Hours
Description
Neutrophils have some zero values pre-challenge, so absolute change is reported instead of percent change: post-pre from baseline to 48 hours
Time Frame
from baseline to 48 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kun P Lu, M.D., PhD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elliot Israel, M.D
Organizational Affiliation
Brigham and Womens Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asthma Research Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Role of the Isomerase Pin-1 in the Development and Treatment of Asthma
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