Imaging Study of the Lungs During an Allergic Asthma Attack

NCT01547286 | Completed Results DMC

• 2 other identifiers: 2007P0023861R01HL086717-01A2
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Atopy

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Percentage Change in the Ratio of Mean-normalized Perfusion Within Ventilation Defective Regions Relative to Outside

  Blood flow relative to the mean blood flow of the lung (mean normalized perfusion) inside areas that have reduced ventilation (Vdefs) relative to outside the Vdefs. Or, another way of writing this is: (Blood flow inside Vdefs/mean blood flow of the lung)/(Blood flow outside Vdefs/mean blood flow of the lung).

  3 hours after allergen administration

• Percentage Change in the Ratio of Mean-normalized Perfusion Within Ventilation Defective Regions Relative to Outside

  Blood flow relative to the mean blood flow of the lung (mean normalized perfusion) inside areas that have reduced ventilation (Vdefs) relative to outside the Vdefs. Or, another way of writing this is: (Blood flow inside Vdefs/mean blood flow of the lung)/(Blood flow outside Vdefs/mean blood flow of the lung).

  7 hours after allergen administration

Secondary Outcomes (2)

• Coefficient of Variation Squared of Perfusion

  3 hours after allergen administration

• Coefficient of Variation Squared of Perfusion

  7 hours after allergen administration

Study Arms (1)

Allergic asthmatic

EXPERIMENTAL

Biological: Standardized Cat Allergen Extract and Standardized Dust Mite Allergen; Radiation: Computed Tomography imaging, functional Positron Emission Tomography imaging; Drug: Nebulized methacholine inhalation

Interventions

Standardized Cat Allergen Extract and Standardized Dust Mite Allergen 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.

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

Allergic asthmatic

Computed Tomography imaging, functional Positron Emission Tomography imaging 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

Allergic asthmatic

Nebulized methacholine inhalation 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.

Also known as: MethaPharm Provocholine

Allergic asthmatic

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Asthma; Respiratory Hypersensitivity

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Robert Scott Harris, MD
• Organization: Massachusetts General Hospital

rsharris@mgh.harvard.edu

617-726-9429

Study Officials

• R. Scott Harris, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 15, 2012
• First Posted: March 7, 2012
• Study Start: May 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 22, 2017
• Results First Posted: April 25, 2017

Record last verified: 2017-10

Locations

US (1)