Liver Disease in Patients With alpha1-antitrypsin Deficiency

NCT02929940 | Unknown DMC

• 1 other identifier: Alpha1-Liver
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

alpha1-antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• Number of participants with Liver fibrosis, Hepatic decompensation, Liver cancer, Death or Liver transplantation

  5 years

Study Arms (4)

PiZZ

Observational

Other: No intervention

PiMZ

Observational

Other: No intervention

Other AATD variants

Observational

Other: No intervention

PiMM (Control)

Observational

Other: No intervention

Interventions

No intervention OTHER

No Intervention, observational

Other AATD variants; PiMM (Control); PiMZ; PiZZ

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• All patients with known AATD (every genotype)
• Relatives of patients with known AATD

You may not qualify if:

• Children
• Pregnant women
• Patients who cannot give informed consent

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (1)

RWTH Aachen University

Aachen, North Rhine-Westphalia, 52074, Germany

RECRUITING

Related Publications (2)

• Spivak 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.

  PMID: 39665869 DERIVED

• 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.

  PMID: 31121167 DERIVED

Related Links

• Alpha1-Liver Website (German)
• Alpha1-Liver Website (English)

Biospecimen

Retention: SAMPLES WITH DNA

Blood specimen for serologic and genetic analyses

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pavel Strnad, MD

  RWTH Aachen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pavel Strnad, MD

CONTACT

0241-80-36606; alpha1-leber@ukaachen.de

Karim Hamesch, MD

CONTACT

0241-80-36606; mail@alpha1-liver.eu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 11, 2016
• Study Start: April 1, 2015
• Primary Completion: April 1, 2020
• Study Completion: December 1, 2020
• Last Updated: May 31, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)