Imaging Study of the Lungs During an Allergic Asthma Attack

October 19, 2017 updated by: Robert Scott Harris, M.D., Massachusetts General Hospital

Redistribution of Pulmonary Perfusion During Bronchoconstriction in Asthma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 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.
Other Names:
  • •Reagents from Greer will be used:
  • •Standardized Cat Hair Extract
  • •Standardized mite extract-Dermatophagoides farinae
  • •Standardized mite extract-Dermatophagoides pteronyssinus
Radiation: 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
Drug: 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.
Other Names:
  • MethaPharm Provocholine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage Change in the Ratio of Mean-normalized Perfusion Within Ventilation Defective Regions Relative to Outside
Time Frame: 3 hours after allergen administration
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
Time Frame: 7 hours after allergen administration
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Coefficient of Variation Squared of Perfusion
Time Frame: 3 hours after allergen administration
Coefficient of variation squared of the perfusion in the imaged lung. This measures the overall heterogeneity of perfusion in the imaged lung.
3 hours after allergen administration
Coefficient of Variation Squared of Perfusion
Time Frame: 7 hours after allergen administration
Coefficient of variation squared of the perfusion in the imaged lung. This measures the overall heterogeneity of perfusion in the imaged lung.
7 hours after allergen administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: R. Scott Harris, MD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 15, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 7, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 22, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2007P002386
  • 1R01HL086717-01A2 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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