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

Asthma Clinical Trial

— Pin1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01691612
• Other study ID #: 2012P001029
• Status: Completed
• Phase: Phase 2
• First received: September 7, 2012
• Last updated: March 31, 2016
• Start date: March 2013
• Est. completion date: May 2015

Study information

• Verified date: March 2016
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Asthma

Intervention

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

Locations

Country	Name	City	State
United States	Asthma Research Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pin1 enzyme activation in BAL-derived eosinophils	We will measure Pin1 activity in BAL-derived eosinophils after House Dust Mite (HDM) allergen challenge.	48 hours	No