Imaging Study of the Lungs During an Allergic Asthma Attack

NCT ID: NCT01547286

Last Updated: 2017-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2013-10-31

Brief Summary

Asthma is a disease of rapidly increasing incidence that already affects more than 17 million people in the United States alone. It has long been known that areas of severely reduced airflow occur in asthma and contribute significantly to the impairment of gas exchange in this disease. However, the extent to which local blood flow changes during an asthmatic attack is unclear. The purpose of this study is using Positron Emission Tomography - Computed Tomography imaging to evaluate how the blood flow changes in the lungs during an asthma attack induced by allergens.

Detailed Description

Asthma is a disease of rapidly increasing incidence that already affects more than 17 million people in the United States alone. It is of major importance to understand the mechanisms responsible for underlying mechanical and physiological changes that occur during asthma exacerbations. The effect of asthma on the pulmonary vasculature is virtually unknown. It has long been known that areas of severely reduced airflow occur in asthma and contribute significantly to the impairment of gas exchange in this disease. However, the extent to which local blood flow changes during an asthmatic attack is unclear. This proposal is designed to evaluate the relevance of potential mechanisms responsible for the blood flow defects seen in our Positron Emission Tomography studies of subjects with asthma and identify factors modifying that perfusion distribution. With this knowledge, it is hoped that a more focused basic research is motivated to understand the fundamental mechanisms behind these processes ultimately targeted to improved asthma therapy. Comparing these measures in healthy subjects and asthmatics patients may lead to methods to improve patient care.

Conditions

Asthma; Atopy

Keywords

Asthma; Allergen Challenge; Cat allergen; Dust mite allergen; Airway Hyper-responsiveness; Positron Emission Tomography - Computed Tomography; Nitrogen isotopes; Blood flow

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Allergic asthmatic

Group Type: EXPERIMENTAL

Standardized Cat Allergen Extract and Standardized Dust Mite Allergen

Intervention Type: BIOLOGICAL

The route of administration will be topical application of the titrated allergen via nebulized droplets to the lungs. The starting dose of allergen will be 3 dose dilutions below the estimated provocative concentration of allergen that causes a 20% fall in Forced Expired Volume in 1 second delivered for 5 minutes at tidal breathing, followed by Forced Expired Volume in 1 second at 10-minute intervals until the lowest Forced Expired Volume in 1 second is established. If the percent of Forced Expired Volume in 1 second fall is \< 20%, the next concentration is given, until the Forced Expired Volume in 1 second falls ≥ 20 percent. When this happens the Forced Expired Volume in 1 second will be followed at 10, 20, 30, 45, and 60 minutes, then hourly for 7 hours. The early asthmatic response is the maximum percent of Forced Expired Volume in 1 second fall between 0 and 3 hours and the late asthmatic response between 3 and 7 hours post allergen challenge.

Computed Tomography imaging, functional Positron Emission Tomography imaging

Intervention Type: RADIATION

Physiology study using Computed Tomography and Positron Emission Tomography imaging with Nitrogen-13 saline as radiotracer; images obtained during the early and late phases after allergen challenge

Nebulized methacholine inhalation

Intervention Type: DRUG

Standard methacholine challenge performed once to determine the subject's dose that causes a 20% fall in Forced Expired Volume in 1 second from baseline.

Interventions

Standardized Cat Allergen Extract and Standardized Dust Mite Allergen

The route of administration will be topical application of the titrated allergen via nebulized droplets to the lungs. The starting dose of allergen will be 3 dose dilutions below the estimated provocative concentration of allergen that causes a 20% fall in Forced Expired Volume in 1 second delivered for 5 minutes at tidal breathing, followed by Forced Expired Volume in 1 second at 10-minute intervals until the lowest Forced Expired Volume in 1 second is established. If the percent of Forced Expired Volume in 1 second fall is \< 20%, the next concentration is given, until the Forced Expired Volume in 1 second falls ≥ 20 percent. When this happens the Forced Expired Volume in 1 second will be followed at 10, 20, 30, 45, and 60 minutes, then hourly for 7 hours. The early asthmatic response is the maximum percent of Forced Expired Volume in 1 second fall between 0 and 3 hours and the late asthmatic response between 3 and 7 hours post allergen challenge.

Intervention Type: BIOLOGICAL

Computed Tomography imaging, functional Positron Emission Tomography imaging

Physiology study using Computed Tomography and Positron Emission Tomography imaging with Nitrogen-13 saline as radiotracer; images obtained during the early and late phases after allergen challenge

Intervention Type: RADIATION

Nebulized methacholine inhalation

Standard methacholine challenge performed once to determine the subject's dose that causes a 20% fall in Forced Expired Volume in 1 second from baseline.

Intervention Type: DRUG

Other Intervention Names

•Reagents from Greer will be used: •Standardized Cat Hair Extract; •Standardized mite extract-Dermatophagoides farinae; •Standardized mite extract-Dermatophagoides pteronyssinus; MethaPharm Provocholine

Eligibility Criteria

Inclusion Criteria

• Mild asthma is defined in the National Institutes of Health 2002 guidelines for the Diagnosis and Management of Asthma. Briefly, people with mild asthma are defined as those with symptoms greater than 2 times a week but less than once per day with normal Forced Expired Volume in 1 second (> 80% predicted)
• Clinical history of allergic symptoms to cat or dust mite allergen and demonstrated skin reactivity
• Life-long absence of cigarette smoking (defined as a lifetime total of less than 5 pack-years); none in 5 years
• Willing and able to give informed consent
• Expressed the desire to participate in an interview with the principal investigator

Exclusion Criteria

• Women of childbearing potential who are documented to be pregnant (based on blood testing) or who are nursing.
• The presence of spontaneous asthmatic episode or clinical evidence of upper respiratory tract infection within the previous 6 weeks.
• Participation in research study involving a drug or biologic during the 30 days prior to the study.
• Intolerance to albuterol, atropine, or lidocaine.
• Antihistamines within 7 days of the screening visit.
• Known exposure to agents that are associated with pulmonary disease (i.e. asbestos, silica).
• Presence of other known pulmonary disease, coronary disease, congestive heart failure, ventricular arrhythmias, history of a cerebrovascular accident, renal failure (or creatinine > 1.5, if known), history of anaphylaxis, cirrhosis or presence of a significant disease, which in the opinion of the principal investigator, would pose a significant risk for the subject or confound the results of the study.
• Use of systemic steroids, increased use of inhaled steroids, beta blockers and mono-amine oxidase inhibitors or a visit for an asthma exacerbation within

1 month of the screening visit.

• A history of asthma-related respiratory failure requiring intubation.
• A history of hospitalization for asthma.
• Subjects with a high possibility of poor compliance with the study as judged by the principal investigator.
• History of contrast dye allergy.
• Unresponsive to bronchodilator agents.
• Quantitative skin prick test at or below a dilution level of standardized cat allergen extract of 1:2048 (4.88 bioequivalent allergy unit/ml)for subjects being challenged with cat allergen.
• Quantitative skin prick test at or below a dilution level of standardized mite allergen extract of 1:2048 (4.88 bioequivalent allergy unit/ml)for subjects being challenged with either mite allergen.
• Subjects who, by participating in one of these studies, will have a cumulative radiation dose exceeding the maximum yearly recommended dose for a research subject (50 milliSieverts).
• Previous participation in one of the protocols in this proposal.
• Contraindication to methacholine challenge testing (Forced Expired Volume in 1 second < 50% predicted or < 1L, heart attack or stroke in last 3 months, uncontrolled hypertension, or known aortic aneurysm).
• Body Mass Index > 32

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Robert Scott Harris, M.D.

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

R. Scott Harris, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

1R01HL086717-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2007P002386

Identifier Type: -

Identifier Source: org_study_id