Imaging Study of the Lungs During an Allergic Asthma Attack - Full Text View

Purpose

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 PET-CT imaging to evaluate how the blood flow changes in the lungs during an asthma attack induced by allergens.

Condition	Intervention
Asthma Atopy	Biological: Standardized Cat Allergen Extract and Standardized Dust Mite Allergen Radiation: CT imaging, functional PET imaging Drug: Nebulized methacholine inhalation

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Redistribution of Pulmonary Perfusion During Bronchoconstriction in Asthma

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Cat Hair

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

mean-normalized perfusion within ventilation defective regions versus outside [ Time Frame: 3 hours after allergen administration ] [ Designated as safety issue: No ]
Blood flow compared to the mean blood flow of the lung (mean normalized perfusion) inside areas that have reduced ventilation (Vdefs) compared to outside the Vdefs.
mean-normalized perfusion within ventilation defective regions versus outside [ Time Frame: 7 hours after allergen administration ] [ Designated as safety issue: No ]
Blood flow compared to the mean blood flow of the lung (mean normalized perfusion) inside areas that have reduced ventilation (Vdefs) compared to outside the Vdefs.

Secondary Outcome Measures:

COV Squared of Perfusion [ Time Frame: 3 hours after allergen administration ] [ Designated as safety issue: No ]
Coefficient of variation squared of the perfusion in the imaged lung. This measures the overall heterogeneity of perfusion in the imaged lung.
COV Squared of Perfusion [ Time Frame: 7 hours after allergen administration ] [ Designated as safety issue: No ]
Coefficient of variation squared of the perfusion in the imaged lung. This measures the overall heterogeneity of perfusion in the imaged lung.

Estimated Enrollment:	20
Study Start Date:	May 2012
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Allergic asthmatic	Biological: 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 PC20-allergen delivered for 5 minutes at tidal breathing, followed by FEV1 at 10-minute intervals until the lowest FEV1 is established. If the %FEV1 fall is < 20%, the next concentration is given, until the FEV1 falls ≥ 20%. When this happens the FEV1 will be followed at 10, 20, 30, 45, and 60 minutes, then hourly for 7 hours. The early asthmatic response is the maximum %FEV1 fall between 0 and 3 hours and the late asthmatic response between 3 and 7 hours post allergen challenge. Other Names: •Reagents from Greer will be used: •Standardized Cat Hair Extract •Standardized mite extract-Dermatophagoides farinae •Standardized mite extract-Dermatophagoides pteronyssinus Radiation: CT imaging, functional PET imaging Physiology study using CT and PET imaging with Nitrogen-13 (13NN) saline as radiotracer; images obtained during the early and late phases after allergen challenge Drug: Nebulized methacholine inhalation Standard methacholine challenge performed once to determine the subject's PC20 dose (the dose that causes a 20% fall in FEV1 from baseline). Other Name: MethaPharm Provocholine

Arms

Assigned Interventions

Experimental: Allergic asthmatic

Biological: 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 PC20-allergen delivered for 5 minutes at tidal breathing, followed by FEV1 at 10-minute intervals until the lowest FEV1 is established. If the %FEV1 fall is < 20%, the next concentration is given, until the FEV1 falls ≥ 20%. When this happens the FEV1 will be followed at 10, 20, 30, 45, and 60 minutes, then hourly for 7 hours. The early asthmatic response is the maximum %FEV1 fall between 0 and 3 hours and the late asthmatic response between 3 and 7 hours post allergen challenge.

Other Names:

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

Radiation: CT imaging, functional PET imaging

Physiology study using CT and PET imaging with Nitrogen-13 (13NN) saline as radiotracer; images obtained during the early and late phases after allergen challenge

Drug: Nebulized methacholine inhalation

Standard methacholine challenge performed once to determine the subject's PC20 dose (the dose that causes a 20% fall in FEV1 from baseline).

Other Name: MethaPharm Provocholine

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 PET 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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 FEV1(> 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 serum beta-HCG 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 MAO 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 BAU/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 BAU/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 mSv).
Previous participation in one of the protocols in this proposal.
Contraindication to methacholine challenge testing (FEV1 < 50% predicted or < 1L, heart attack or stroke in last 3 months, uncontrolled hypertension, or known aortic aneurysm).
Body Mass Index (BMI ) > 32

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01547286

Contacts

Contact: Mamary Kone, MD, MPH	617-726-1082	mkone@partners.org
Contact: R. Scott Harris, MD	617-726-9426	rharris@partners.org

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Sub-Investigator: Jose G Venegas, PHD
Sub-Investigator: Tilo Winkler, PHD
Sub-Investigator: Benjamin Medoff, MD
Sub-Investigator: Daniel Hamilos, MD

Sponsors and Collaborators

Massachusetts General Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

R. Scott Harris, MD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Robert Scott Harris, M.D., Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT01547286 History of Changes
Other Study ID Numbers:	2007P002386, 1R01HL086717-01A2
Study First Received:	February 15, 2012
Last Updated:	March 11, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

Asthma
Allergen Challenge
Cat allergen
Dust mite allergen

Airway Hyper-responsiveness
PET-CT
Nitrogen isotopes
Blood flow

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Methacholine Chloride
Miotics
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Parasympathomimetics
Bronchoconstrictor Agents
Respiratory System Agents
Therapeutic Uses
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013