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Recruiting NCT01851642

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

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

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: History and physical exam., Blood draw., Pulmonary function testing., Albuterol inhaler..
Who it may be relevant to
Registry conditions: Alpha-1 Antitrypsin Deficiency, AAT Deficiency, AATD, Cystic Fibrosis (CF). Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

The Role of Conformational Diseases on Macrophage Function

Overview

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

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.

Interventions

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

Primary outcome measures

  • Evaluation of macrophage function. [Time frame: On average, within 30 days from the time the blood is collected.]
Secondary outcome measures (3)
  • Comparison of the amount of alpha-1 antitrypsin in the blood. [Time frame: On average, within 30 days from the time the blood was collected.]
  • Comparison of the amount of an inflammatory marker in the blood, called C-reactive protein. [Time frame: On average, within 30 days from the time the blood is collected.]
  • Evaluation of lung function. [Time frame: On average, within 30 days from the time the testing is completed.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model
Case-control

Study locations

United States · 1 center
  • Shands at the University of Florida — Gainesville

Publications

  • 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. PMID 8109800
  • 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. PMID 1083527
  • 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. PMID 1084290
  • 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. PMID 1608473
  • 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. PMID 12464659
  • 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. PMID 16183649
  • 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. PMID 12438434
  • 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. PMID 16449189

Identifiers

NCT: NCT01851642 · IRB201501051 · 699 · 08-2007

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗