Alpha-1 Antitrypsin DeficiencyNCT01851642
Lung Disease and Its Affect on the Work of White Blood Cells in the Lungs
An observational study of Alpha-1 Antitrypsin Deficiency and AAT Deficiency, run by University of Florida at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency, AAT Deficiency, AATD
- What is being tested?
- History and physical exam., Blood draw. and Pulmonary function testing.
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 220 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Aug 2007to 20 Jul 2033
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Alpha-1 Antitrypsin (AAT) Deficient subjects, Cystic Fibrosis(CF) subjects with mutation Delta F508, and subjects without either diagnosis.
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Shands at the University of Florida
Gainesville, Florida, 32610
Allison Faunce, B.A., 352-273-8666, Allison.Faunce@medicine.ufl.edu
Michelle Owens, RN,BSN, 352-273-6339, Sandra.Owens@medicine.ufl.edu
About this study
Official title: The Role of Conformational Diseases on Macrophage Function
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.
Read the 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.
- Being tested
- History and physical exam., Blood draw., Pulmonary function testing., Albuterol inhaler.
- Keywords
- Macrophage, Alpha-1 Antitrypsin Deficiency, Cystic Fibrosis
- Medical subject headings
- alpha 1-Antitrypsin Deficiency, Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
History and physical exam.Procedure or surgery
Also called H&P
At every study visit, participant's will be asked about their medical history and will have a physical exam.
Blood draw.Procedure or surgery
Also called Phlebotomy
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.Procedure or surgery
Also called PFTs
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.Drug
Also called Ventolin, Proventil, Proventil-HFA, AccuNeb
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: History and physical exam.; Procedure: Blood draw.; Procedure: Pulmonary function testing.; Drug: Albuterol inhaler. | |
| 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. Receives: Procedure: History and physical exam.; Procedure: Blood draw.; Procedure: Pulmonary function testing.; Drug: Albuterol inhaler. | |
| 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. Receives: Procedure: History and physical exam.; Procedure: Blood draw.; Procedure: Pulmonary function testing.; Drug: Albuterol inhaler. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of macrophage function.
From every study participant, we will collect blood from a vein through the placement of an intravenous catheter (IV). We will complete various experiments that will allow us to see how well each participant's macrophage cells are working.
Measured: On average, within 30 days from the time the blood is collected.
Secondary outcomes (3)
Comparison of the amount of alpha-1 antitrypsin in the blood.
From every study participant, we will collect blood from a vein through an IV.
Measured: 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.
From every study participant, we will collect blood from a vein through and IV.
Measured: On average, within 30 days from the time the blood is collected.
Evaluation of lung function.
Lung function testing will be done on every study participant. This is is done by forcefully blowing into a tube on at least 3 separate occasions. Albuterol, an inhaled medication used to expand lung airways, will be given after lung function testing and then the testing will be repeated after 30 minutes.
Measured: On average, within 30 days from the time the testing is completed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study start9 Aug 2007
- Primary completion20 Jul 2032 (estimated)
- Study completion20 Jul 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Alpha-1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Karina Serban, MD, Principal investigator, University of Florida, College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851642
- Sponsor's protocol ID
- IRB201501051
- Other IDs
- 699, 08-2007
- Status last verified
- Nov 2025
- First submitted
- 25 Apr 2013
- Last updated
- 6 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Enrolled subjects may request a copy of their clinical testing done while enrolled in the clinical trial. All other data used for publication purposes will be de-identified.
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.
PubMed 8109800Yoshida 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.
PubMed 1083527Jeppsson 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.
PubMed 1084290Lomas 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.
PubMed 1608473Perlmutter 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.
PubMed 12464659Hidvegi 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.
PubMed 16183649Kaufman 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.
PubMed 12438434Oda 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.
PubMed 16449189Seager 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.
PubMed 15183091Newman 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.
PubMed 9031492
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Conformational Diseases on Macrophage Function
- ClinicalTrials.gov ID
- NCT01851642
- Acronym / sponsor ID
- IRB201501051
- Keywords
- Macrophage, Alpha-1 Antitrypsin Deficiency, Cystic Fibrosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- 9 Aug 2007 (actual)
- Primary completion
- 20 Jul 2032 (estimated)
- Study completion
- 20 Jul 2033 (estimated)
- First posted
- 10 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AAT Deficiency | – | Procedure: History and physical exam., Procedure: Blood draw., Procedure: Pulmonary function testing., Drug: Albuterol inhaler.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. |
| Cystic Fibrosis | – | Procedure: History and physical exam., Procedure: Blood draw., Procedure: Pulmonary function testing., Drug: Albuterol inhaler.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. |
| Without Lung Disease Diagnosis | – | Procedure: History and physical exam., Procedure: Blood draw., Procedure: Pulmonary function testing., Drug: Albuterol inhaler.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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Alpha-1 Antitrypsin (AAT) Deficient subjects, Cystic Fibrosis(CF) subjects with mutation Delta F508, and subjects without either diagnosis.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| History and physical exam.Also: H&PAt every study visit, participant's will be asked about their medical history and will have a physical exam. | Procedure or surgery | AAT Deficiency, Cystic Fibrosis, Without Lung Disease Diagnosis |
| Blood draw.Also: PhlebotomyAt 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 or surgery | AAT Deficiency, Cystic Fibrosis, Without Lung Disease Diagnosis |
| Pulmonary function testing.Also: PFTsAt 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. | Procedure or surgery | AAT Deficiency, Cystic Fibrosis, Without Lung Disease Diagnosis |
| Albuterol inhaler.Also: Ventolin, Proventil, Proventil-HFA, AccuNebAt 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. | Drug | AAT Deficiency, Cystic Fibrosis, Without Lung Disease Diagnosis |
Primary outcome
Evaluation of macrophage function.
Time frame: On average, within 30 days from the time the blood is collected.
From every study participant, we will collect blood from a vein through the placement of an intravenous catheter (IV). We will complete various experiments that will allow us to see how well each participant's macrophage cells are working.
3 secondary outcomes
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2025.
- Background: PubMed 8109800Blank CA, Brantly M. Clinical features and molecular characteristics of alpha 1-antitrypsin deficiency. Ann Allergy. 1994 Feb;72(2):105-20; quiz 120-2.
- Background: PubMed 1083527Yoshida 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.
- Background: PubMed 1084290Jeppsson 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.
- Background: PubMed 1608473Lomas 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.
- Background: PubMed 12464659Perlmutter 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.
- Background: PubMed 16183649Hidvegi 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.
- Background: PubMed 12438434Kaufman 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.
- Background: PubMed 16449189Oda 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.
- Background: PubMed 15183091Seager 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.
- Background: PubMed 9031492Newman 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.
- University of Florida, Division of Pulmonary Medicine, Critical Care \& Sleep MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Enrolled subjects may request a copy of their clinical testing done while enrolled in the clinical trial. All other data used for publication purposes will be de-identified.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Karina Serban, MD principal investigator
University of Florida, College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alpha-1 Antitrypsin Deficiency and AAT Deficiency, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Allison E. Faunce, B.A. (352-273-8666, Allison.Faunce@medicine.ufl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of macrophage function. (time frame: On average, within 30 days from the time the blood is collected.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01851642, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2025.