Clinical trial NCT03237494: TRAMmoniTTR Study Genetic Screening of an At-risk Population for HATTR and Monitoring of TTR Positive Subjects
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Transthyretin Amyloidosis
Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy
Polyneuropathies
Cardiomyopathies
Keywords: Peripheral Nervous System Diseases
Transthyretin Amyloidosis
Transthyretin-related familial amyloid polyneuropathy
Transthyretin-related familial amyloid cardiomyopathy
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
Collaborators: name: Alnylam Pharmaceuticals
First posted: 2017-08-02
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants at risk for Hereditary Transthyretin Amyloidosis (hATTR) and participants diagnosed with hATTR

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Analysis of prevalance of hATTR mutations among a cohort of participants at risk for hATTR.
timeFrame: 4 years
measure: To monitor clinical status in TTR positive subjects.
timeFrame: 4 years
Secondary outcomes:
measure: Establishment of biomarker/s in TTR positive cohort.
timeFrame: 4 years
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Kepler Universitätsklinikum, Klinik für Interne 1 - Kardiologie und internistische Intensivmedizin; Cardiology
city: Linz
country: Austria
facility: Kepler Universitätsklinikum, Neuromed Campus; Neurology
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, Neurology
city: Ahaus
country: Germany
facility: Klinikum Westmünsterland GmbH, I. Medizinische Klinik und Interventionelle Kardiologie
city: Altenburg
country: Germany
facility: Kreiskrankenhaus Altenburg, Neurology
city: Arnsdorf
country: Germany
facility: Sächsisches Krankenhaus Arnsdorf, Akademisches Lehrkrankenhaus der TU Dresden, Neurology
city: Aschaffenburg
country: Germany
facility: Gemeinschaftspraxis Neurologie & Psychiatrie im Stadtpalais
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH, Klinik für Kardiologie, Cardiology
city: Bad Neustadt An Der Saale
country: Germany
facility: RHÖN-KLINIKUM Campus Bad Neustadt, Neurology
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin Funktionsdiagnostik und Stationen, Cardiology
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Klinik für Neurologie, Neurology
city: Berlin
country: Germany
facility: Sana Klinikum Lichtenberg
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin - Campus Virchow Klinikum (CVK), Cardiology
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld, Klinik für Kardiologie und internistische Intensivmedizin, Cardiology
city: Bielefeld
country: Germany
facility: Evangelisches Klinikum Bethel gGmbH v. Bodelschwinghsche Stiftungen Bethel, Neurology
city: Bremen
country: Germany
facility: Klinikum Bremen Mitte gGmbH, Neurologische Klinik, Neurology
city: Bremen
country: Germany
facility: Gesundheit Nord gGmbH - Klinikverband Bremen
city: Buchholz In Der Nordheide
country: Germany
facility: Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Cardiology
city: Buchholz In Der Nordheide
country: Germany
facility: Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Neurology
city: Celle
country: Germany
facility: Allgemeines Krankenhaus Celle, Neurology
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus gGmbH
city: Datteln
country: Germany
facility: St. Vincenz Krankenhaus Datteln, Medizinische Klinik II, Cardiology
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH,Stroke-Unit und Neurologische Intensivstation, Neurology
city: Düsseldorf
country: Germany
facility: LVR Klinikum Düsseldorf, Neurology
city: Eberswalde
country: Germany
facility: Martin Gropius Krankenhaus, Klinik für Neurologie, Neurology
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Cardiology
city: Essen
country: Germany
facility: Alfried Krupp Krankenhaus Rüttenscheid, Neurology
city: Essen
country: Germany
facility: Contilia Herz- und Gefäßzentrum, Elisabeth-Krankenhaus Essen, Cardiology
city: Friedberg
country: Germany
facility: Kliniken an der Paar Friedberg Krankenhaus, Cardiology
city: Fulda
country: Germany
facility: Herz-Thorax-Zentrum Fulda, Klinikum Fulda gAG, Universitätsmedizin Marburg - Campus Fulda, Cardiology
city: Giessen
country: Germany
facility: University of Giessen-Marburg, Neurology
city: Greifswald
country: Germany
facility: Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität, Neurology
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen - Herzzentrum; Cardiology
city: Haar
country: Germany
facility: kbo-Isar-Amper-Klinikum München-Ost, Klinik für Neurologie, Neurology
city: Halle (Saale)
country: Germany
facility: Martin-Luther-Universität, Universitätsklinik und Poliklinik für Neurologie, Neurology
city: Halle (Saale)
country: Germany
facility: Universitätsklinik und Poliklinik für Innere Medizin III, Cardiology
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg, Klinik für Neurologie
city: Hamburg
country: Germany
facility: Universitäres Herzzentrum Hamburg, Klinik für Allgemeine und Interventionelle Kardiologie, Universitätsklinikum Hamburg-Eppendorf, Cardiology
city: Hamburg
country: Germany
facility: Neurologie Neuer Wall, Fachärzte für Neurologie & Psychiatrie, Neurology
city: Hamburg
country: Germany
facility: Albertinen-Krankenhaus, Cardiology
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona, Neurologische Abteilung mit überregionaler Stroke Unit, Neurophysiologie und Neurologischer Intensivmedizin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Neurologie; Neurology
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie und Pneumologie, Cardiology
city: Hoyerswerda
country: Germany
facility: Lausitzer Seenland Klinikum GmbH, Klinik für Neurologie, Neurology
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Neurology
city: Jena
country: Germany
facility: Universitätsklinikum Jena Klinik für Innere Medizin I
city: Kassel
country: Germany
facility: DRK-Kliniken Nordhessen gGmbH , Klinik für Neurologie und Klinische Neurophysiologie, Neurology
city: Krefeld
country: Germany
facility: Alexianer Krefeld GmbH, Krankenhaus Maria Hilf, Neurology
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig, Neurology
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH
city: Lübben
country: Germany
facility: Asklepios Fachklinikum Lübben, Neurology
city: Lübeck
country: Germany
facility: Universitäres Herzzentrum Lübeck, Medizinische Klinik II
city: Lübeck
country: Germany
facility: Sana Kliniken Lübeck GmbH, Medizinische Klinik II
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Mainz
country: Germany
facility: DRK Schmerz-Zentrum, Neurology
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurologie; Neurology
city: Mannheim
country: Germany
facility: Diakonissen Speyer-Mannheim, Diakonissenkrankenhaus Mannheim, Neurology
city: Mosbach
country: Germany
facility: Neckar-Odenwald Kliniken gGmbH, Kreiskrankenhaus Mosbach, Kardiologie der Klinik für Innere Medizin
city: Mühlhausen
country: Germany
facility: Ökumenisches Hainich Klinikum gGmbH, Neurology
city: München
country: Germany
facility: Friedrich-Baur-Institut, Neurologische Klinik und Poliklinik, Neurology
city: München
country: Germany
facility: Kardiologie München Nord, Cardiology
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München, Klinikum Großhadern, Neurologische Klinik und Poliklinik & Deutsches Schwindel- und Gleichgewichtszentrum DSGZ, Neurology
city: München
country: Germany
facility: Klinik und Poliklinik für Neurologie, Klinikum rechts der Isar, Technische Universität München
city: München
country: Germany
facility: Praxis für Neurologie, Neurology
city: Neuruppin
country: Germany
facility: Ruppiner Kliniken GmbH,Hochschulklinikum der MHB, Neurology
city: Neuruppin
country: Germany
facility: UKRB Universitätsklinikum Ruppin Brandenburg
city: Perleberg
country: Germany
facility: Kreiskrankenhaus Prignitz gGmbH, Neurology
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brüder Regensburg, Klinik für Neurologie, Neurology
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Cardiology
city: Sande
country: Germany
facility: Nordwest-Krankenhaus Sanderbusch gGmbH, Neurologische Klinik, Neurology
city: Schkeuditz
country: Germany
facility: Sächsisches Krankenhaus Altscherbitz, Neurology
city: Siegen
country: Germany
facility: Jung-Stilling Klinikum Siegen, Diakonie Westfalen Süd Neuro, Neurogeriatrie, Neurology
city: Stade
country: Germany
facility: Elbe Klinikum Stade
city: Teupitz
country: Germany
facility: Asklepios Fachklinikum Teupitz, Neurology
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Zentrum für Neurologie
city: Ulm
country: Germany
facility: NeuroPoint, Neurology
city: Ulm
country: Germany
facility: University of Ulm, Neurology
city: Weimar
country: Germany
facility: Sophien-u.Hufeland-Klinikum, Klinik für Neurologie und Klinische Neurophysiologie, Neurology
city: Wermsdorf
country: Germany
facility: Fachkrankenhaus Hubertusburg gGmbH, Neurologische Klinik, Neurology
city: Wismar
country: Germany
facility: Sana HANSE Klinikum Wismar, Klinik für Neurologie, Neurology
city: Wolfratshausen
country: Germany
facility: Praxis für Neurologie, Neurology
city: Luzern
country: Switzerland
facility: Luzerner Kantonspital, Cardiology
city: Olten
country: Switzerland
facility: Solothurner Spitäler AG, Bürgerspital Solothurn, Cardiology
city: Zug
country: Switzerland
facility: Praxisgemeinschaft für Kardiologie, Innere Medizin und Psychosomatische Medizin, Cardiology
Study officials:
affiliation: Centogene GmbH
name: Peter Bauer, Prof.
role: STUDY_CHAIR
References: