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AzTrials

Alpha 1-antitrypsin Deficiency (AATD)NCT07639996

Natural Course and Molecular Basis of Alpha 1- Antitrypsin Deficiency-associated Liver Disease.

An observational study of Alpha 1-antitrypsin Deficiency (AATD), run by Assiut University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial summary

To define the course of AATD-associated liver disease. To use the obtained samples for biomedical research which includes: 1. Search for serum-based disease biomarkers and the associated molecular pathways. 2. Multi-omic spatial analysis of human AATD-LD. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Alpha 1-antitrypsin Deficiency (AATD)
What is being tested?
Multi-omic spatial analysis
How many people
45 participants
Where
No sites listed yet
Study dates
1 Oct 2026to 30 Sep 2028
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
  • Adult, Older adult

Study population: * Adult patients (≥18 years) with genetically confirmed alpha-1 antitrypsin deficiency (Pi*ZZ genotype). * Availability of longitudinal clinical follow-up data (minimum 5 years) within the AATD consortium. * At least one documented liver assessment including liver stiffness measurement (LSM) and serum-based fibrosis markers. * Availability of stored serum samples for proteomic analysis. * For translational analyses: availability of liver tissue samples (pediatric or adult) and/or induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells.

Who may be able to join

  • Adult patients (≥18 years) with genetically confirmed alpha-1 antitrypsin deficiency (Pi*ZZ genotype).
  • Availability of longitudinal clinical follow-up data (minimum 5 years) within the AATD consortium.
  • At least one documented liver assessment including liver stiffness measurement (LSM) and serum-based fibrosis markers.
  • Availability of stored serum samples for proteomic analysis.
  • For translational analyses: availability of liver tissue samples (pediatric or adult) and/or induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells.

Who cannot join

  • Presence of other chronic liver diseases (e.g., viral hepatitis, autoimmune hepatitis) that may confound fibrosis assessment.
  • History of liver transplantation prior to study inclusion.
  • Incomplete clinical, laboratory, or follow-up data.
  • Poor-quality or insufficient biological samples for proteomic or molecular analyses.
  • Patients lost to follow-up or with unreliable longitudinal data

About this study

  • To define the course of AATD-associated liver disease.
  • To use the obtained samples for biomedical research which includes:
  1. Search for serum-based disease biomarkers and the associated molecular pathways.
  2. Multi-omic spatial analysis of human AATD-LD.
Read the detailed description

AATD is one of the most common, potentially lethal genetic conditions and results from mutations in alpha-1 antitrypsin (AAT), an abundant serine protease inhibitor (SERPIN) produced primarily in hepatocytes. The majority of severe AATD cases result from a homozygous PiZ mutation termed PiZZ that leads to a rapid polymerization of the mutated protein and its retention in the endoplasmic reticulum (ER) of hepatocytes. The consecutive lack of AAT in circulation increases proteolytic digestion of lung tissue and predisposes to chronic obstructive pulmonary disease and lung emphysema. The hepatic AAT misfolding confers a proteotoxic stress and may lead to both pediatric and adult liver disease (pAATD-LD/aAATD-LD). The former becomes apparent as neonatal jaundice and constitutes one of the most common causes of pediatric liver transplantation while the latter emerges mostly at >40 years of age as significant liver fibrosis and occurs more frequently in subjects with metabolic risk factors such as obesity and diabetes mellitus.

Much less is known about pAATD-LD that is considered a more cholestatic condition with less obvious AAT accumulation. Moreover, the exact relationship between AAT accumulation and development of AATD-LD remains unclear.

A major obstacle when studying AATD-LD is the lack of a suitable experimental model system. While transgenic animals overexpressing PiZ have been widely used, they have several disadvantages such as presence of multiple PiZ copies as well as inability to reproduce pAATD-LD. To circumvent that, analyses of human specimen as well as human induced pluripotent stem cells (iPSC) derived hepatocyte like cells (HLCs) are essential. Therefore, our research aims to obtain further insights into the process of AAT accumulation as well as to delineate the mechanistic differences between pediatric and adult AATD-LD.

Being tested
Multi-omic spatial analysis
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.

  • Multi-omic spatial analysisDiagnostic test

    conduction of spatial multi-omic analyses comparing pediatric and adult liver tissues. This will include proteomic and transcriptomic mapping to understand how AAT accumulation and ductular reactions differ between the two forms.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Search for serum-based disease biomarkers and the associated molecular pathways

    Measured: Eight months of performing serum proteomics to identify biomarkers that reflect liver disease severity and predict poor outcomes

Secondary outcomes (1)

  1. Multi-omic spatial analysis of human AATD-LD.

    Measured: Eight months of conduction of spatial multi-omic analyses comparing pediatric and adult liver tissues. This will include proteomic and transcriptomic mapping to understand how AAT accumulation and ductular reactions differ between the two forms.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2026
  2. Study start1 Oct 2026 (estimated)
  3. Primary completion30 Sep 2027 (estimated)
  4. Study completion30 Sep 2028 (estimated)

Resources

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
Cross-sectional
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07639996
Sponsor's protocol ID
Alpha 1 antitrypsin deficiency
Status last verified
May 2026
First submitted
1 Jun 2026
Last updated
10 Jun 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Townsend SA, Edgar RG, Ellis PR, Kantas D, Newsome PN, Turner AM. Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease. Aliment Pharmacol Ther. 2018 Apr;47(7):877-885. doi: 10.1111/apt.14537. Epub 2018 Feb 15.

    PubMed 29446109

  • Tafaleng EN, Chakraborty S, Han B, Hale P, Wu W, Soto-Gutierrez A, Feghali-Bostwick CA, Wilson AA, Kotton DN, Nagaya M, Strom SC, Roy-Chowdhury J, Stolz DB, Perlmutter DH, Fox IJ. Induced pluripotent stem cells model personalized variations in liver disease resulting from alpha1-antitrypsin deficiency. Hepatology. 2015 Jul;62(1):147-57. doi: 10.1002/hep.27753. Epub 2015 Apr 13.

    PubMed 25690322

  • Strnad P, McElvaney NG, Lomas DA. Alpha1-Antitrypsin Deficiency. N Engl J Med. 2020 Apr 9;382(15):1443-1455. doi: 10.1056/NEJMra1910234. No abstract available.

    PubMed 32268028

  • Ruiz M, Lacaille F, Schrader C, Pons M, Socha P, Krag A, Sturm E, Bouchecareilh M, Strnad P. Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency. Semin Liver Dis. 2023 Aug;43(3):258-266. doi: 10.1055/a-2122-7674. Epub 2023 Jul 4.

    PubMed 37402396

  • Patel D, McAllister SL, Teckman JH. Alpha-1 antitrypsin deficiency liver disease. Transl Gastroenterol Hepatol. 2021 Apr 5;6:23. doi: 10.21037/tgh.2020.02.23. eCollection 2021.

    PubMed 33824927

  • Ncube A, Bewersdorf L, Spitzhorn LS, Loerch C, Bohndorf M, Graffmann N, May L, Amzou S, Fromme M, Wruck W, Strnad P, Adjaye J. Generation of two Alpha-I antitrypsin deficiency patient-derived induced pluripotent stem cell lines ISRM-AATD-iPSC-1 (HHUUKDi011-A) and ISRM-AATD-iPSC-2 (HHUUKDi012-A). Stem Cell Res. 2023 Sep;71:103171. doi: 10.1016/j.scr.2023.103171. Epub 2023 Jul 23.

    PubMed 37506509

  • Kaserman JE, Hurley K, Dodge M, Villacorta-Martin C, Vedaie M, Jean JC, Liberti DC, James MF, Higgins MI, Lee NJ, Washko GR, San Jose Estepar R, Teckman J, Kotton DN, Wilson AA. A Highly Phenotyped Open Access Repository of Alpha-1 Antitrypsin Deficiency Pluripotent Stem Cells. Stem Cell Reports. 2020 Jul 14;15(1):242-255. doi: 10.1016/j.stemcr.2020.06.006. Epub 2020 Jul 2.

    PubMed 32619491

  • Hamesch 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

  • Greene CM, Marciniak SJ, Teckman J, Ferrarotti I, Brantly ML, Lomas DA, Stoller JK, McElvaney NG. alpha1-Antitrypsin deficiency. Nat Rev Dis Primers. 2016 Jul 28;2:16051. doi: 10.1038/nrdp.2016.51.

    PubMed 27465791

  • Fromme M, Schneider CV, Trautwein C, Brunetti-Pierri N, Strnad P. Alpha-1 antitrypsin deficiency: A re-surfacing adult liver disorder. J Hepatol. 2022 Apr;76(4):946-958. doi: 10.1016/j.jhep.2021.11.022. Epub 2021 Nov 27.

    PubMed 34848258

Questions about this trial

What is this clinical trial studying?

An observational study of Alpha 1-antitrypsin Deficiency (AATD), run by Assiut University.

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 5 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: opening soon, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Search for serum-based disease biomarkers and the associated molecular pathways (time frame: Eight months of performing serum proteomics to identify biomarkers that reflect liver disease severity and predict poor outcomes). 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 NCT07639996, 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 10 Jun 2026.

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