Lung Disease and Its Affect on the Work of White Blood Cells in the Lungs

NCT ID: NCT01851642

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

220 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-08-09

Study Completion Date

2033-07-20

Brief Summary

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The purpose of this study is to look at how Alpha-1-antitrypsin (AAT) deficiency and Cystic Fibrosis (CF) affect white blood cells in the lungs, called macrophages, and their ability to work.

Detailed Description

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AAT deficiency is a genetic disorder that affects around 100,000 people in the USA, including 1-3% of all people diagnosed with chronic obstructive pulmonary disease (COPD). In AAT deficient people diagnosed with COPD, it was originally believed the cause of the disease was due to a lack of supply of alpha-1 antitrypsin. However, early information gathered in our laboratory suggests another cause of the development of COPD and the progressing of the disease may be due to a malfunction in macrophages.

CF is also a genetic disorder which affects 1/300 births among the Caucasian population. One of the main symptoms of CF is inflammation of the lung tissue. Lung macrophages play a major role in lung inflammation as well as in helping to resolve the inflammation.

Inflammation is an important defense of the body. It is the body's response to infection causing germs and things that may cause irritation, as well as, a way for the body to repair damaged tissue.

We suggest that the effects of AAT deficiency and CF decreases the inflammation response in the lungs and also restricts the ability of macrophages to correct that inflammation once it occurs.

Conditions

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Alpha-1 Antitrypsin Deficiency AAT Deficiency AATD Cystic Fibrosis (CF)

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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AAT Deficiency

Those diagnosed with Alpha-1 Antitrypsin (AAT) Deficiency. At every study visit, a history and physical exam (H\&P), blood draw, and pulmonary function testing (PFTs) with the use of an albuterol inhaler will be done.

History and physical exam.

Intervention Type PROCEDURE

At every study visit, participant's will be asked about their medical history and will have a physical exam.

Blood draw.

Intervention Type PROCEDURE

At each study visit, participants will have an intravenous catheter (IV) placed in one of their veins and blood will be drawn from the IV for study testing.

Pulmonary function testing.

Intervention Type PROCEDURE

At every study visit, participants will have their lung function assessed. This is done by blowing forcefully at least 3 times into a tube. Testing will be done two times; before and after the use of an Albuterol inhaler.

Albuterol inhaler.

Intervention Type DRUG

At every study visit, participating subjects will take 2 puffs of an Albuterol inhaler after the first set of PFTs, but before the second set of PFTs. There will be at least a 30 minute period after the use of the Albuterol inhaler and the second set of PFTs.

Cystic Fibrosis

Those diagnosed with Cystic Fibrosis (CF) with mutation Delta F508. At every study visit, a history and physical exam (H\&P), blood draw, and pulmonary function testing (PFTs) with the use of an albuterol inhaler will be done.

History and physical exam.

Intervention Type PROCEDURE

At every study visit, participant's will be asked about their medical history and will have a physical exam.

Blood draw.

Intervention Type PROCEDURE

At each study visit, participants will have an intravenous catheter (IV) placed in one of their veins and blood will be drawn from the IV for study testing.

Pulmonary function testing.

Intervention Type PROCEDURE

At every study visit, participants will have their lung function assessed. This is done by blowing forcefully at least 3 times into a tube. Testing will be done two times; before and after the use of an Albuterol inhaler.

Albuterol inhaler.

Intervention Type DRUG

At every study visit, participating subjects will take 2 puffs of an Albuterol inhaler after the first set of PFTs, but before the second set of PFTs. There will be at least a 30 minute period after the use of the Albuterol inhaler and the second set of PFTs.

Without Lung Disease Diagnosis

Those without the diagnosis of AAT Deficiency or CF. At every study visit, a history and physical exam (H\&P), blood draw, and pulmonary function testing (PFTs) with the use of an albuterol inhaler will be done.

History and physical exam.

Intervention Type PROCEDURE

At every study visit, participant's will be asked about their medical history and will have a physical exam.

Blood draw.

Intervention Type PROCEDURE

At each study visit, participants will have an intravenous catheter (IV) placed in one of their veins and blood will be drawn from the IV for study testing.

Pulmonary function testing.

Intervention Type PROCEDURE

At every study visit, participants will have their lung function assessed. This is done by blowing forcefully at least 3 times into a tube. Testing will be done two times; before and after the use of an Albuterol inhaler.

Albuterol inhaler.

Intervention Type DRUG

At every study visit, participating subjects will take 2 puffs of an Albuterol inhaler after the first set of PFTs, but before the second set of PFTs. There will be at least a 30 minute period after the use of the Albuterol inhaler and the second set of PFTs.

Interventions

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History and physical exam.

At every study visit, participant's will be asked about their medical history and will have a physical exam.

Intervention Type PROCEDURE

Blood draw.

At each study visit, participants will have an intravenous catheter (IV) placed in one of their veins and blood will be drawn from the IV for study testing.

Intervention Type PROCEDURE

Pulmonary function testing.

At every study visit, participants will have their lung function assessed. This is done by blowing forcefully at least 3 times into a tube. Testing will be done two times; before and after the use of an Albuterol inhaler.

Intervention Type PROCEDURE

Albuterol inhaler.

At every study visit, participating subjects will take 2 puffs of an Albuterol inhaler after the first set of PFTs, but before the second set of PFTs. There will be at least a 30 minute period after the use of the Albuterol inhaler and the second set of PFTs.

Intervention Type DRUG

Other Intervention Names

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H&P Phlebotomy PFTs Ventolin Proventil Proventil-HFA AccuNeb Vospire ProAir

Eligibility Criteria

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Inclusion Criteria

* Signed informed consent
* Male or female 18 years of age or older
* Negative pregnancy test for women of childbearing potential
* Hemoglobin \>12.5 g/dl measured on the day of participation
* Negative urine nicotine test

Exclusion Criteria

* Pregnancy or breastfeeding
* Weight \< 50 kg
* History of anemia requiring blood transfusions, erythropoietin supplementation, or iron supplementation within the past 36 months
* Known hemoglobin \<12.5 g/dl within the past 90 days
* Systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \>100 mmHg
* Poor venous access
* Large volume blood donation (\>200 ml or 7 ounces) within the previous 56 days (e.g. blood donation for the purposes of blood banking)
* Clinically significant cardiac, hemostatic or neurological impairment or any other significant medical condition that, in the opinion of the investigator would affect subject safety (e.g., recent myocardial infarction, history of prolonged bleeding time, cerebral vascular accident, advanced cancer or uncontrolled medical condition)
* Psychiatric or cognitive disturbance or illness that would affect subject safety
* Current smoker
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Florida

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karina Serban, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida, College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine

Locations

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Shands at the University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Allison E. Faunce, B.A.

Role: CONTACT

352-273-8666

Michelle Owens, RN, BSN

Role: CONTACT

352-273-6339

Facility Contacts

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Allison Faunce, B.A.

Role: primary

352-273-8666

Michelle Owens, RN,BSN

Role: backup

352-273-6339

References

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Blank CA, Brantly M. Clinical features and molecular characteristics of alpha 1-antitrypsin deficiency. Ann Allergy. 1994 Feb;72(2):105-20; quiz 120-2.

Reference Type BACKGROUND
PMID: 8109800 (View on PubMed)

Yoshida A, Lieberman J, Gaidulis L, Ewing C. Molecular abnormality of human alpha1-antitrypsin variant (Pi-ZZ) associated with plasma activity deficiency. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1324-8. doi: 10.1073/pnas.73.4.1324.

Reference Type BACKGROUND
PMID: 1083527 (View on PubMed)

Jeppsson JO. Amino acid substitution Glu leads to Lys alpha1-antitrypsin PiZ. FEBS Lett. 1976 Jun 1;65(2):195-7. doi: 10.1016/0014-5793(76)80478-4. No abstract available.

Reference Type BACKGROUND
PMID: 1084290 (View on PubMed)

Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature. 1992 Jun 18;357(6379):605-7. doi: 10.1038/357605a0.

Reference Type BACKGROUND
PMID: 1608473 (View on PubMed)

Perlmutter DH. Liver injury in alpha1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury. J Clin Invest. 2002 Dec;110(11):1579-83. doi: 10.1172/JCI16787. No abstract available.

Reference Type BACKGROUND
PMID: 12464659 (View on PubMed)

Hidvegi T, Schmidt BZ, Hale P, Perlmutter DH. Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response. J Biol Chem. 2005 Nov 25;280(47):39002-15. doi: 10.1074/jbc.M508652200. Epub 2005 Sep 23.

Reference Type BACKGROUND
PMID: 16183649 (View on PubMed)

Kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest. 2002 Nov;110(10):1389-98. doi: 10.1172/JCI16886. No abstract available.

Reference Type BACKGROUND
PMID: 12438434 (View on PubMed)

Oda Y, Okada T, Yoshida H, Kaufman RJ, Nagata K, Mori K. Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation. J Cell Biol. 2006 Jan 30;172(3):383-93. doi: 10.1083/jcb.200507057.

Reference Type BACKGROUND
PMID: 16449189 (View on PubMed)

Seager Danciger J, Lutz M, Hama S, Cruz D, Castrillo A, Lazaro J, Phillips R, Premack B, Berliner J. Method for large scale isolation, culture and cryopreservation of human monocytes suitable for chemotaxis, cellular adhesion assays, macrophage and dendritic cell differentiation. J Immunol Methods. 2004 May;288(1-2):123-34. doi: 10.1016/j.jim.2004.03.003.

Reference Type BACKGROUND
PMID: 15183091 (View on PubMed)

Newman BH. Donor reactions and injuries from whole blood donation. Transfus Med Rev. 1997 Jan;11(1):64-75. doi: 10.1016/s0887-7963(97)80011-9.

Reference Type BACKGROUND
PMID: 9031492 (View on PubMed)

Related Links

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http://pulmonary.medicine.ufl.edu/

University of Florida, Division of Pulmonary Medicine, Critical Care \& Sleep Medicine

Other Identifiers

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699

Identifier Type: OTHER

Identifier Source: secondary_id

08-2007

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201501051

Identifier Type: -

Identifier Source: org_study_id

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