The Use of High Resolution Chest Computed Tomography in Alpha-1 Antitrypsin Deficiency (QUANTUM-1)

This study has been completed.
Sponsor:
Collaborators:
Alpha-1 Foundation
Information provided by (Responsible Party):
Charlie Strange, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00532805
First received: September 18, 2007
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

Individuals with a deficiency of alpha-1 antitrypsin (AAT) often develop emphysema. Traditional lung function tests may not be the most accurate way to measure the progression of emphysema. This study will compare high resolution computed tomography (CT) scans to spirometry to measure the progression of emphysema.


Condition
Alpha-1 Antitrypsin Deficiency

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: QUANTitative Chest Computed Tomography UnMasking Emphysema Progression in Alpha-1 Antitrypsin Deficiency

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • CT density slope [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

50 cc of serum at visits baseline, 6 months, 12 months, 18 months, 24 months and 36 months will be retained. These are kept at the University of Florida in the laboratory of Dr. Mark Brantly.

There is an associated but independent DNA collection that is done if the patient is willing through an independent study and consent process with the University of Florida Alpha-1 DNA and Tissue Bank. This is a public resource with a scientific advisory committee with samples available for researcher access.


Enrollment: 49
Study Start Date: August 2007
Study Completion Date: April 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Detailed Description:

AAT deficiency is a genetic disorder associated with emphysema. Spirometry, the lung function test that measures how well the lungs exhale air, is used to diagnose and track the progression of emphysema. Some studies have suggested that forced expiratory volume in 1 second (FEV1) measurements, a type of spirometry test, may lack accuracy in detecting disease progression in cases of severe AAT deficiency. Another method, high resolution chest CT scans, may be more accurate at measuring the progression of emphysema. The purpose of this study is to determine if high resolution CT scans are better at detecting the progression of emphysema than lung function tests. Results from this study may lead to the development of a more accurate way to assess lung tissue loss and may improve the understanding of lung destruction in AAT deficiency.

This study will last 4 years and will enroll people with AAT deficiency who have nearly normal lung function test results. Study visits, each lasting about 4 hours, will occur at baseline and months 6, 12, 18, 24, and 36. At each visit, participants will undergo lung function tests, a CT scan, blood collection, and a physical exam. Female participants will have urine collected for a pregnancy test. All participants will also complete questionnaires to assess health status and lung function. Study researchers will call participants every 2 months to collect information on lung disease symptoms and medication changes.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Individuals with alpha-1 antitrypsin who have nearly normal lung function tests. Participants will be identified from patients of the investigators, physician referral, and the Alpha-1 Foundation Research Registry.

Criteria

Inclusion Criteria:

  • Diagnosis of AAT deficiency, as determined by both of the following conditions:

    1. Serum A1-P1 levels less than 11uM or 80 mg/dL
    2. Protease inhibitor phenotype Z (PiZZ) or Znull phenotype confirmed by gene probe analysis. Previous serum levels and phenotype results are acceptable if documented from a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
  • FEV1 greater than or equal to 80% of the predicted value

Exclusion Criteria:

  • Pregnant or intending to become pregnant within 4 years of study entry
  • Previous lung transplantation
  • Sibling of a participant who is already enrolled in the study
  • Unable to attend scheduled clinic visits
  • Currently smokes cigarettes or marijuana or quit smoking cigarettes or marijuana in the 1 year prior to study entry
  • Current or planned use of oral tobacco products or nicotine replacement products
  • Evidence of significant long-term or acute inflammation outside the lung, including connective diseases, panniculitis, or acute infection
  • Unwilling to alter bronchodilator medications for 24 hours prior to scheduled quantitative CT (QCT) scans
  • Musculoskeletal disease that limits exercise by walking
  • Required to take any of the following medications within 48 hours of scheduled lung function testing: dicyclomine (Bentyl), propantheline (Pro-Banthine), mepenzolate (Cantil), methscopolamine (Pamine), and scopolamine (Transderm-Scop)
  • Known allergy or intolerance to tiotropium or albuterol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532805

Locations
United States, Colorado
National Jewish Medical and Research Center
Denver, Colorado, United States
United States, Florida
University of Florida Medical Center
Gainesville, Florida, United States
United States, Massachusetts
Harvard/Brigham and Women's Hospital
Boston, Massachusetts, United States
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
United States, Oregon
Oregon Health and Sciences University
Portland, Oregon, United States
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States
Sponsors and Collaborators
Medical University of South Carolina
Alpha-1 Foundation
Investigators
Study Chair: Charlie Strange, MD Medical University of South Carolina
  More Information

No publications provided

Responsible Party: Charlie Strange, Professor of Pulmonary Medicine, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00532805     History of Changes
Other Study ID Numbers: RDCRN 5701, 1U54RR019498-01
Study First Received: September 18, 2007
Last Updated: December 17, 2012
Health Authority: United States: Federal Government

Keywords provided by Medical University of South Carolina:
Alpha 1-Antitrypsin Deficiency

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Alpha 1-Antitrypsin
Protein C Inhibitor
Digestive System Diseases
Emphysema
Genetic Diseases, Inborn
Liver Diseases
Lung Diseases
Pathologic Processes
Respiratory Tract Diseases
Subcutaneous Emphysema
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Trypsin Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014