TRAMmoniTTR Study Genetic Screening of an At-risk Population for hATTR and Monitoring of TTR Positive Subjects

Cardiomyopathies Clinical Trial

— TRAMmoniTTR  

Official title:

Genetic Screening of an At-risk Population for Hereditary TransthyRetin-related AMyloidosis and Longitudinal Monitoring of TTR Positive Subjects- A Multicenter Epidemiological Longitudinal Protocol

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03237494
• Other study ID #: TRAM2 analysis
• Status: Recruiting
• Start date: July 20, 2017
• Est. completion date: April 30, 2025

Study information

• Verified date: September 2023
• Source: CENTOGENE GmbH Rostock
• Contact: Sabine Roesner
• Phone: +49 381 80113657
• Email: sabine.roesner[@]centogene.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

National, multicenter, epidemiological, longitudinal protocol to investigate the hATTR prevalence in an at-risk population for Hereditary Transthyretin Amyloidosis (hATTR) and subjects diagnosed with hATTR, to monitor the clinical status in TTR positive subjects and to establish hATTR biomarker/s

Description:

Hereditary TransThyRetin Amyloidosis (hATTR) is a slowly progressive condition, that is transmitted as an autosomal dominant trait and is characterized by abnormal extracellular deposits of fibrillar, misfolded proteins (amyloid fibrils) in the body. Amyloid fibrils can be deposited in different body compartments, such as the nerves, heart, gastrointestinal tract, kidneys and brain, causing severe structural changes. More than 30 proteins can trigger the formation of amyloid fibrils, 5 of which can infiltrate the heart and cause cardiac amyloidosis.

One of these amyloidogenic protein is transthyretin, formerly known as prealbumin. Transthyretin (TTR) is found primarily in the serum (secreted by the liver) and cerebrospinal fluid (secreted by the choroid plexus) and functions as a carrier for the hormone thyroxine (T4) and retinol-binding protein (bound to retinol or vitamin A). The destabilization of the TTR protein and the formation of misfolded TTR.

It is the goal of this study to investigate the prevalence of Hereditary Transthyretin-related Amyloidosis (hATTR) in a cohort of 5.000 subjects are at risk for Hereditary Transthyretin Amyloidosis (hATTR) and subjects diagnosed with hATTR, to monitor the clinical status in TTR positive subjects and to establish hATTR biomarker/s.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent is obtained from the participant

• The participant is 18 years of age or older

• The participant has no diagnosis of alcoholism according to international guidelines

• The participant has not undergone chemotherapy for any carcinoma

AND

The participant is at risk for hATTR due to two or more the factors listed below:

• cardiomyopathy or polyneuropathy with no obvious etiology atypical Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or Motor Neuron Disease (MND)

• autonomic dysfunction

• hypertrophic cardiomyopathy or heart failure with preserved ejection fraction Left Ventricular Hypertrophy (LVH)

• bilateral carpal tunnel syndrome

• spinal stenosis or spinal radiculopathy

• gait disorders

• ocular changes involving vitreous opacities

• unexplained weight loss >5kg

• renal abnormalities

• family history of hATTR

• based on imaging or biopsy suspected for the wild type TTR (ATTR) and not genetically tested for hATTR

OR • The participant is diagnosed with hATTR

OR

• The participant is a 1st or 2nd degree relative of the TTR positive subject

Exclusion Criteria

• Informed consent is not obtained from the participant

• The participant is younger than 18 years of age

• The participant has a diagnosis of alcoholism according to International guidelines

• The participant has undergone chemotherapy for any carcinoma

• The participant is not at risk for hATTR

Related Conditions & MeSH terms

• Amyloid Neuropathies
• Amyloid Neuropathies, Familial
• Amyloidosis
• Cardiomyopathies
• Polyneuropathies
• Transthyretin Amyloidosis
• Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy
• Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy

Locations

Country	Name	City	State
Austria	Kepler Universitätsklinikum, Klinik für Interne 1 - Kardiologie und internistische Intensivmedizin; Cardiology	Linz
Austria	Kepler Universitätsklinikum, Neuromed Campus; Neurology	Linz
Germany	Universitätsklinikum Aachen, Neurology	Aachen
Germany	Klinikum Westmünsterland GmbH, I. Medizinische Klinik und Interventionelle Kardiologie	Ahaus
Germany	Kreiskrankenhaus Altenburg, Neurology	Altenburg
Germany	Sächsisches Krankenhaus Arnsdorf, Akademisches Lehrkrankenhaus der TU Dresden, Neurology	Arnsdorf
Germany	Gemeinschaftspraxis Neurologie & Psychiatrie im Stadtpalais	Aschaffenburg
Germany	Kerckhoff-Klinik GmbH, Klinik für Kardiologie, Cardiology	Bad Nauheim
Germany	RHÖN-KLINIKUM Campus Bad Neustadt, Neurology	Bad Neustadt An Der Saale
Germany	Charité - Universitätsmedizin Berlin Funktionsdiagnostik und Stationen, Cardiology	Berlin
Germany	Charité Universitätsmedizin Berlin - Campus Virchow Klinikum (CVK), Cardiology	Berlin
Germany	Charité Universitätsmedizin Berlin, Klinik für Neurologie, Neurology	Berlin
Germany	Evangelisches Klinikum Bethel gGmbH v. Bodelschwinghsche Stiftungen Bethel, Neurology	Bielefeld
Germany	Klinikum Bielefeld, Klinik für Kardiologie und internistische Intensivmedizin, Cardiology	Bielefeld
Germany	Gesundheit Nord gGmbH - Klinikverband Bremen	Bremen
Germany	Klinikum Bremen Mitte gGmbH, Neurologische Klinik, Neurology	Bremen
Germany	Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Cardiology	Buchholz In Der Nordheide
Germany	Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Neurology	Buchholz In Der Nordheide
Germany	Allgemeines Krankenhaus Celle, Neurology	Celle
Germany	Carl-Thiem-Klinikum Cottbus gGmbH	Cottbus
Germany	St. Vincenz Krankenhaus Datteln, Medizinische Klinik II, Cardiology	Datteln
Germany	Klinikum Dortmund gGmbH,Stroke-Unit und Neurologische Intensivstation, Neurology	Dortmund
Germany	LVR Klinikum Düsseldorf, Neurology	Düsseldorf
Germany	Martin Gropius Krankenhaus, Klinik für Neurologie, Neurology	Eberswalde
Germany	Universitätsklinikum Erlangen, Cardiology	Erlangen
Germany	Alfried Krupp Krankenhaus Rüttenscheid, Neurology	Essen
Germany	Contilia Herz- und Gefäßzentrum, Elisabeth-Krankenhaus Essen, Cardiology	Essen
Germany	Kliniken an der Paar Friedberg Krankenhaus, Cardiology	Friedberg
Germany	Herz-Thorax-Zentrum Fulda, Klinikum Fulda gAG, Universitätsmedizin Marburg - Campus Fulda, Cardiology	Fulda
Germany	University of Giessen-Marburg, Neurology	Giessen
Germany	Universitätsmedizin Göttingen - Herzzentrum; Cardiology	Göttingen
Germany	Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität, Neurology	Greifswald
Germany	kbo-Isar-Amper-Klinikum München-Ost, Klinik für Neurologie, Neurology	Haar
Germany	Martin-Luther-Universität, Universitätsklinik und Poliklinik für Neurologie, Neurology	Halle (Saale)
Germany	Universitätsklinik und Poliklinik für Innere Medizin III, Cardiology	Halle (Saale)
Germany	Albertinen-Krankenhaus, Cardiology	Hamburg
Germany	Asklepios Klinik Altona, Neurologische Abteilung mit überregionaler Stroke Unit, Neurophysiologie und Neurologischer Intensivmedizin	Hamburg
Germany	Asklepios Klinik St. Georg, Klinik für Neurologie	Hamburg
Germany	Neurologie Neuer Wall, Fachärzte für Neurologie & Psychiatrie, Neurology	Hamburg
Germany	Universitäres Herzzentrum Hamburg, Klinik für Allgemeine und Interventionelle Kardiologie, Universitätsklinikum Hamburg-Eppendorf, Cardiology	Hamburg
Germany	Medizinische Hochschule Hannover, Klinik für Neurologie; Neurology	Hannover
Germany	Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie und Pneumologie, Cardiology	Heidelberg
Germany	Lausitzer Seenland Klinikum GmbH, Klinik für Neurologie, Neurology	Hoyerswerda
Germany	Universitätsklinikum Jena, Neurology	Jena
Germany	DRK-Kliniken Nordhessen gGmbH , Klinik für Neurologie und Klinische Neurophysiologie, Neurology	Kassel
Germany	Alexianer Krefeld GmbH, Krankenhaus Maria Hilf, Neurology	Krefeld
Germany	Klinikum St. Georg gGmbH	Leipzig
Germany	Universitaetsklinikum Leipzig, Neurology	Leipzig
Germany	Asklepios Fachklinikum Lübben, Neurology	Lübben
Germany	Sana Kliniken Lübeck GmbH, Medizinische Klinik II	Lübeck
Germany	Universitäres Herzzentrum Lübeck, Medizinische Klinik II	Lübeck
Germany	DRK Schmerz-Zentrum, Neurology	Mainz
Germany	Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurologie; Neurology	Mainz
Germany	Diakonissen Speyer-Mannheim, Diakonissenkrankenhaus Mannheim, Neurology	Mannheim
Germany	Neckar-Odenwald Kliniken gGmbH, Kreiskrankenhaus Mosbach, Kardiologie der Klinik für Innere Medizin	Mosbach
Germany	Ökumenisches Hainich Klinikum gGmbH, Neurology	Mühlhausen
Germany	Friedrich-Baur-Institut, Neurologische Klinik und Poliklinik, Neurology	München
Germany	Kardiologie München Nord, Cardiology	München
Germany	Klinik und Poliklinik für Neurologie, Klinikum rechts der Isar, Technische Universität München	München
Germany	Ludwig-Maximilians-Universität München, Klinikum Großhadern, Neurologische Klinik und Poliklinik & Deutsches Schwindel- und Gleichgewichtszentrum DSGZ, Neurology	München
Germany	Praxis für Neurologie, Neurology	München
Germany	Ruppiner Kliniken GmbH,Hochschulklinikum der MHB, Neurology	Neuruppin
Germany	Kreiskrankenhaus Prignitz gGmbH, Neurology	Perleberg
Germany	Krankenhaus Barmherzige Brüder Regensburg, Klinik für Neurologie, Neurology	Regensburg
Germany	Universitätsklinikum Regensburg, Cardiology	Regensburg
Germany	Nordwest-Krankenhaus Sanderbusch gGmbH, Neurologische Klinik, Neurology	Sande
Germany	Sächsisches Krankenhaus Altscherbitz, Neurology	Schkeuditz
Germany	Jung-Stilling Klinikum Siegen, Diakonie Westfalen Süd Neuro, Neurogeriatrie, Neurology	Siegen
Germany	Elbe Klinikum Stade	Stade
Germany	Asklepios Fachklinikum Teupitz, Neurology	Teupitz
Germany	Universitätsklinikum Tübingen, Zentrum für Neurologie	Tübingen
Germany	NeuroPoint, Neurology	Ulm
Germany	University of Ulm, Neurology	Ulm
Germany	Sophien-u.Hufeland-Klinikum, Klinik für Neurologie und Klinische Neurophysiologie, Neurology	Weimar
Germany	Fachkrankenhaus Hubertusburg gGmbH, Neurologische Klinik, Neurology	Wermsdorf
Germany	Sana HANSE Klinikum Wismar, Klinik für Neurologie, Neurology	Wismar
Germany	Praxis für Neurologie, Neurology	Wolfratshausen
Switzerland	Luzerner Kantonspital, Cardiology	Luzern
Switzerland	Solothurner Spitäler AG, Bürgerspital Solothurn, Cardiology	Olten
Switzerland	Praxisgemeinschaft für Kardiologie, Innere Medizin und Psychosomatische Medizin, Cardiology	Zug

Sponsors (2)

Lead Sponsor	Collaborator
CENTOGENE GmbH Rostock	Alnylam Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of prevalance of hATTR mutations among a cohort of participants at risk for hATTR.	DBS-based genetic analyses of TTR gene will be perfomed via the combination of the Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification.	4 years
Primary	To monitor clinical status in TTR positive subjects.	8 Follow up visits within 24 months	4 years
Secondary	Establishment of biomarker/s in TTR positive cohort.	hATTR-positive samples will be analyzed for the identification of potential biomarkers (based on MS/MS-Tandem spectroscopy) and compared with the merged control samples in order establish a HAE specific biomarker.	4 years

External Links

•   Centogene GmbH web page