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

NCT01691612 | Completed Phase 2 Results

• 1 other identifier: 2012P001029
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

Role of Pin-1 enzyme in Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Lymphocytes at 48 Hours

  from baseline to 48 hours

• Percent Change From Baseline in the Percentage of Total White Blood Cell That Were Macrophages at 48 Hours

  from baseline to 48 hours

• Change From Baseline in the Percentage of Total White Blood Cell That Were Neutrophils at 48 Hours

  from baseline to 48 hours

Study Arms (1)

D. pteronyssinus allergens

EXPERIMENTAL

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

Interventions

installation of D. pteronyssinus allergens BIOLOGICAL

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

Also known as: D. pteronyssinus allergens exposure

D. pteronyssinus allergens

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Asthma Research Center

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Elliot Israel, M.D.
• Organization: Brigham & Women's Hospital

eisrael@partners.org

617-732-8110

Study Officials

• Kun P Lu, M.D., PhD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• Elliot Israel, M.D

  Brigham and Womens Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: September 7, 2012
• First Posted: September 25, 2012
• Study Start: March 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: July 3, 2017
• Results First Posted: July 3, 2017

Record last verified: 2017-06

Locations

US (1)