alpha1-antitrypsin DeficiencyNCT02929940
Liver Disease in Patients With alpha1-antitrypsin Deficiency
An observational study of alpha1-antitrypsin Deficiency, run by RWTH Aachen University at 1 site in Germany.
Trial summary
Alpha1-antitrypsin deficiency (AATD) is the third most common genetic disorder leading to death worldwide. Apart from lung disease, AATD also leads to liver involvement in up to 50% of patients. Hence, liver involvement is the second most common cause of morbidity and mortality in AATD patients. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- alpha1-antitrypsin Deficiency
- How many people
- 500 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2015to Dec 2020
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: All patients with alpha1-antitrypsin deficiency (AATD) and their relatives. AATD is the third most common genetic disorder leading to death worldwide. Apart from lung disease, AATD also leads to liver involvement in up to 50% of patients. Hence, liver involvement is the second most common cause of morbidity and mortality in AATD patients. The natural history of disease is not well understood and specific therapies are lacking. Accordingly, the AATD-related liver disease is still largely being neglected by both the patients and the healthcare professionals.
Who may be able to join
- All patients with known AATD (every genotype)
- Relatives of patients with known AATD
Who cannot join
- Children
- Pregnant women
- Patients who cannot give informed consent
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
RWTH Aachen University
Aachen, North Rhine-Westphalia, 52074
Pavel Strnad, MD, 0241-80-36606, pstrnad@ukaachen.de
Karim Hamesch, MD, 0241-80-36606, khamesch@ukaachen.de
About this study
Official title: Multi-center Study of the Liver Disease in European Patients With alpha1-antitrypsin Deficiency
Alpha1-antitrypsin deficiency (AATD) is the third most common genetic disorder leading to death worldwide. Apart from lung disease, AATD also leads to liver involvement in up to 50% of patients. Hence, liver involvement is the second most common cause of morbidity and mortality in AATD patients. But the natural history of disease in adults is not well understood and specific therapies are still in the phase of preclinical studies. Despite these facts and the therapeutic and preventative potential, the AATD-related liver disease is still largely being neglected by both the patients and the healthcare professionals.
To improve the hepatologic care of patients with AATD, the investigators initiated a prospective multi-center study in Europe that systematically evaluates the liver function in these patients and their relatives. The investigators cooperate with both patient organizations as well as with lung centers specialized on AATD-related lung disease.
Read the detailed description
Alpha1-antitrypsin deficiency (AAT deficiency) is a frequently overlooked metabolic disorder. Apart from lung disease, AAT deficiency also leads to liver disease. This can affect people of all ages and all ethnic groups. Although involvement of the liver is the second most common cause of decreased quality of life and life expectancy in Alpha1 patients, no preventative care plan, like that one implemented to avoid lung involvement, has yet been drawn up.
Chronic liver involvement therefore often remains undetected until a very late stage in diagnosed cases of AAT deficiency. This is compounded by the fact that the patients affected generally have only unspecific symptoms if any at all. Moreover, routine diagnostic measurements (e.g. liver function tests) often reveal no abnormalities. In the case of a late diagnosis, the diverse complications of liver disease can no longer be effectively prevented.
Liver involvement in AAT deficiency can lead to liver cirrhosis or liver cancer. Liver cirrhosis is the life-threatening consequence of many liver disorders and carries a poor prognosis. Besides AAT deficiency, many other - potentially treatable - conditions, such as viral hepatitis, excessive alcohol consumption and diabetes, can cause liver damage. Liver cirrhosis itself leads to many, often life-threatening secondary disorders such as heavy bleeding or liver cancer. It is therefore crucial that liver disorders such as AAT deficiency are diagnosed at an early stage, so as to prevent complications and to treat concomitant risk factors.
The investigators collaborate with various patient support groups and other hospitals specialising in AAT deficiency-associated lung disease. Together with their collaborators, the investigators hope to improve the care of affected patients and help to bring about therapeutic advances.
The aim of this study is to clarify how liver function is modified in patients with AAT deficiency. For this, among other things, the investigators use:
(i) modern ultrasound-based scanners for non-invasive measurement of the degree of liver scarring.
(ii) Specialized liver parameters in blood samples, which also provide information on any existing liver disorders (iii) Questionnaire.
Study participants receive a full, cost-free analysis of their individual liver involvement and are given appropriate recommendations for disease prevention. The examinations provide a relief to many and to everybody,the investigators are able to offer an individual liver damage prevention plan.
All adult patients (of every genotype) as well as any family members interested will be studied and advised. Besides the specialist clinic in Aachen (Germany), free examinations throughout and even outside of Germany will be offered.
- Conditions
- alpha1-antitrypsin Deficiency
- Being tested
- No intervention
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No Intervention, observational
| Study group | Role | What they receive |
|---|---|---|
| PiZZ | Observational Receives: Other: No intervention | |
| PiMZ | Observational Receives: Other: No intervention | |
| Other AATD variants | Observational Receives: Other: No intervention | |
| PiMM (Control) | Observational Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Liver fibrosis, Hepatic decompensation, Liver cancer, Death or Liver transplantation
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2016 (estimated)
- Study startApr 2015
- Primary completionApr 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for alpha1-antitrypsin DeficiencyStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pavel Strnad, MD, Principal investigator, RWTH Aachen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02929940
- Sponsor's protocol ID
- Alpha1-Liver
- Status last verified
- May 2017
- First submitted
- 6 Oct 2016
- Last updated
- 31 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Balasubramani S, Remih K, Karl AS, Borchert JA, Schrader C, Fromme M, Kayatekin C, Zhang B, Levit M, Krishnaswami P, van Eekeren LE, Joosten LAB, Otten T, Tomanova P, Strnad P. Affinity Proteomics-Based Non-Invasive Detection of Clinically Significant Liver Disease. Aliment Pharmacol Ther. 2026 Jul;64(1):74-88. doi: 10.1111/apt.70656. Epub 2026 Apr 16.
PubMed 41992602Spivak I, Guldiken N, Usachov V, Schaap F, Damink SWMO, Bouchecareilh M, Lehmann A, Fu L, Mo FR, Ensari GK, Hufnagel F, Fromme M, Preisinger C, Strnad P. Alpha-1 Antitrypsin Inclusions Sequester GRP78 in a Bile Acid-Inducible Manner. Liver Int. 2025 Jan;45(1):e16207. doi: 10.1111/liv.16207.
PubMed 39665869Hamesch K, Mandorfer M, Pereira VM, Moeller LS, Pons M, Dolman GE, Reichert MC, Schneider CV, Woditsch V, Voss J, Lindhauer C, Fromme M, Spivak I, Guldiken N, Zhou B, Arslanow A, Schaefer B, Zoller H, Aigner E, Reiberger T, Wetzel M, Siegmund B, Simoes C, Gaspar R, Maia L, Costa D, Bento-Miranda M, van Helden J, Yagmur E, Bzdok D, Stolk J, Gleiber W, Knipel V, Windisch W, Mahadeva R, Bals R, Koczulla R, Barrecheguren M, Miravitlles M, Janciauskiene S, Stickel F, Lammert F, Liberal R, Genesca J, Griffiths WJ, Trauner M, Krag A, Trautwein C, Strnad P; European Alpha1-Liver Study Group. Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation. Gastroenterology. 2019 Sep;157(3):705-719.e18. doi: 10.1053/j.gastro.2019.05.013. Epub 2019 May 20.
PubMed 31121167
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center Study of the Liver Disease in European Patients With alpha1-antitrypsin Deficiency
- ClinicalTrials.gov ID
- NCT02929940
- Acronym / sponsor ID
- Alpha1-Liver
- Conditions
- alpha1-antitrypsin Deficiency
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 11 Oct 2016 (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.
Alpha1-antitrypsin deficiency (AATD) is the third most common genetic disorder leading to death worldwide. Apart from lung disease, AATD also leads to liver involvement in up to 50% of patients. Hence, liver involvement is the second most common cause of morbidity and mortality in AATD patients. But the natural history of disease in adults is not well understood and specific therapies are still in the phase of preclinical studies. Despite these facts and the therapeutic and preventative potential, the AATD-related liver disease is still largely being neglected by both the patients and the healthcare professionals.
To improve the hepatologic care of patients with AATD, the investigators initiated a prospective multi-center study in Europe that systematically evaluates the liver function in these patients and their relatives. The investigators cooperate with both patient organizations as well as with lung centers specialized on AATD-related lung disease.
Detailed description
Alpha1-antitrypsin deficiency (AAT deficiency) is a frequently overlooked metabolic disorder. Apart from lung disease, AAT deficiency also leads to liver disease. This can affect people of all ages and all ethnic groups. Although involvement of the liver is the second most common cause of decreased quality of life and life expectancy in Alpha1 patients, no preventative care plan, like that one implemented to avoid lung involvement, has yet been drawn up.
Chronic liver involvement therefore often remains undetected until a very late stage in diagnosed cases of AAT deficiency. This is compounded by the fact that the patients affected generally have only unspecific symptoms if any at all. Moreover, routine diagnostic measurements (e.g. liver function tests) often reveal no abnormalities. In the case of a late diagnosis, the diverse complications of liver disease can no longer be effectively prevented.
Liver involvement in AAT deficiency can lead to liver cirrhosis or liver cancer. Liver cirrhosis is the life-threatening consequence of many liver disorders and carries a poor prognosis. Besides AAT deficiency, many other - potentially treatable - conditions, such as viral hepatitis, excessive alcohol consumption and diabetes, can cause liver damage. Liver cirrhosis itself leads to many, often life-threatening secondary disorders such as heavy bleeding or liver cancer. It is therefore crucial that liver disorders such as AAT deficiency are diagnosed at an early stage, so as to prevent complications and to treat concomitant risk factors.
The investigators collaborate with various patient support groups and other hospitals specialising in AAT deficiency-associated lung disease. Together with their collaborators, the investigators hope to improve the care of affected patients and help to bring about therapeutic advances.
The aim of this study is to clarify how liver function is modified in patients with AAT deficiency. For this, among other things, the investigators use:
(i) modern ultrasound-based scanners for non-invasive measurement of the degree of liver scarring.
(ii) Specialized liver parameters in blood samples, which also provide information on any existing liver disorders (iii) Questionnaire.
Study participants receive a full, cost-free analysis of their individual liver involvement and are given appropriate recommendations for disease prevention. The examinations provide a relief to many and to everybody,the investigators are able to offer an individual liver damage prevention plan.
All adult patients (of every genotype) as well as any family members interested will be studied and advised. Besides the specialist clinic in Aachen (Germany), free examinations throughout and even outside of Germany will be offered.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| PiZZ | – | Other: No interventionObservational |
| PiMZ | – | Other: No interventionObservational |
| Other AATD variants | – | Other: No interventionObservational |
| PiMM (Control) | – | Other: No interventionObservational |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- All patients with alpha1-antitrypsin deficiency (AATD) and their relatives. AATD is the third most common genetic disorder leading to death worldwide. Apart from lung disease, AATD also leads to liver involvement in up to 50% of patients. Hence, liver involvement is the second most common cause of morbidity and mortality in AATD patients. The natural history of disease is not well understood and specific therapies are lacking. Accordingly, the AATD-related liver disease is still largely being neglected by both the patients and the healthcare professionals.
Key inclusion criteria (2 listed)
- All patients with known AATD (every genotype)
- Relatives of patients with known AATD
Key exclusion criteria (3 listed)
- Children
- Pregnant women
- Patients who cannot give informed consent
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 |
|---|---|---|
| No interventionNo Intervention, observational | Other | Other AATD variants, PiMM (Control), PiMZ, PiZZ |
Primary outcome
Number of participants with Liver fibrosis, Hepatic decompensation, Liver cancer, Death or Liver transplantation
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2017.
- Derived from this study: PubMed 41992602Balasubramani S, Remih K, Karl AS, Borchert JA, Schrader C, Fromme M, Kayatekin C, Zhang B, Levit M, Krishnaswami P, van Eekeren LE, Joosten LAB, Otten T, Tomanova P, Strnad P. Affinity Proteomics-Based Non-Invasive Detection of Clinically Significant Liver Disease. Aliment Pharmacol Ther. 2026 Jul;64(1):74-88. doi: 10.1111/apt.70656. Epub 2026 Apr 16.
- Derived from this study: PubMed 39665869Spivak I, Guldiken N, Usachov V, Schaap F, Damink SWMO, Bouchecareilh M, Lehmann A, Fu L, Mo FR, Ensari GK, Hufnagel F, Fromme M, Preisinger C, Strnad P. Alpha-1 Antitrypsin Inclusions Sequester GRP78 in a Bile Acid-Inducible Manner. Liver Int. 2025 Jan;45(1):e16207. doi: 10.1111/liv.16207.
- Derived from this study: PubMed 31121167Hamesch K, Mandorfer M, Pereira VM, Moeller LS, Pons M, Dolman GE, Reichert MC, Schneider CV, Woditsch V, Voss J, Lindhauer C, Fromme M, Spivak I, Guldiken N, Zhou B, Arslanow A, Schaefer B, Zoller H, Aigner E, Reiberger T, Wetzel M, Siegmund B, Simoes C, Gaspar R, Maia L, Costa D, Bento-Miranda M, van Helden J, Yagmur E, Bzdok D, Stolk J, Gleiber W, Knipel V, Windisch W, Mahadeva R, Bals R, Koczulla R, Barrecheguren M, Miravitlles M, Janciauskiene S, Stickel F, Lammert F, Liberal R, Genesca J, Griffiths WJ, Trauner M, Krag A, Trautwein C, Strnad P; European Alpha1-Liver Study Group. Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation. Gastroenterology. 2019 Sep;157(3):705-719.e18. doi: 10.1053/j.gastro.2019.05.013. Epub 2019 May 20.
- Alpha1-Liver Website (German)Link provided by the sponsor.
- Alpha1-Liver Website (English)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Pavel Strnad, MD principal investigator
RWTH Aachen University
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 alpha1-antitrypsin Deficiency, run by RWTH Aachen University at 1 site in Germany.
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 2 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 31 May 2017. 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 Germany. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pavel Strnad, MD (0241-80-36606, alpha1-leber@ukaachen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Liver fibrosis, Hepatic decompensation, Liver cancer, Death or Liver transplantation (time frame: 5 years). 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 NCT02929940, which also lists 3 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 31 May 2017.