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CompletedNCT03237494TRAMmoniTTRUpdated Jun 29, 2025

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

An observational study in Transthyretin Amyloidosis, Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy and Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy, sponsored by CENTOGENE GmbH Rostock. Completed at 84 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-29.

Sponsored by CENTOGENE GmbH Rostock · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
5,028
Ages
18 Years and older
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Probability sample

Study population

Participants at risk for Hereditary Transthyretin Amyloidosis (hATTR) and participants diagnosed with hATTR

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

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
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
5,028 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Participants at risk for hATTR and participants diagnosed with hATTR

    Participants 18 years of age or older

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 4 years

  2. To monitor clinical status in TTR positive subjects.

    8 Follow up visits within 24 months

    Time frame: 4 years

Secondary outcomes

  1. 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.

    Time frame: 4 years

06

Study locations

84 sites
  • Kepler Universitätsklinikum, Klinik für Interne 1 - Kardiologie und internistische Intensivmedizin; Cardiology
    Linz, 4021, Austria
  • Kepler Universitätsklinikum, Neuromed Campus; Neurology
    Linz, 4021, Austria
  • Universitätsklinikum Aachen, Neurology
    Aachen, 52074, Germany
  • Klinikum Westmünsterland GmbH, I. Medizinische Klinik und Interventionelle Kardiologie
    Ahaus, 48683, Germany
  • Kreiskrankenhaus Altenburg, Neurology
    Altenburg, 04600, Germany
  • Sächsisches Krankenhaus Arnsdorf, Akademisches Lehrkrankenhaus der TU Dresden, Neurology
    Arnsdorf, 01477, Germany
  • Gemeinschaftspraxis Neurologie & Psychiatrie im Stadtpalais
    Aschaffenburg, 63739, Germany
  • Kerckhoff-Klinik GmbH, Klinik für Kardiologie, Cardiology
    Bad Nauheim, 61231, Germany
  • RHÖN-KLINIKUM Campus Bad Neustadt, Neurology
    Bad Neustadt an der Saale, 97616, Germany
  • Charité - Universitätsmedizin Berlin Funktionsdiagnostik und Stationen, Cardiology
    Berlin, 10117, Germany
  • Charité Universitätsmedizin Berlin, Klinik für Neurologie, Neurology
    Berlin, 10117, Germany
  • Sana Klinikum Lichtenberg
    Berlin, 101365, Germany
  • Charité Universitätsmedizin Berlin - Campus Virchow Klinikum (CVK), Cardiology
    Berlin, 13353, Germany
  • Klinikum Bielefeld, Klinik für Kardiologie und internistische Intensivmedizin, Cardiology
    Bielefeld, 33604, Germany
  • Evangelisches Klinikum Bethel gGmbH v. Bodelschwinghsche Stiftungen Bethel, Neurology
    Bielefeld, 33617, Germany
  • Klinikum Bremen Mitte gGmbH, Neurologische Klinik, Neurology
    Bremen, 28177, Germany
  • Gesundheit Nord gGmbH - Klinikverband Bremen
    Bremen, 28211, Germany
  • Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Cardiology
    Buchholz in der Nordheide, 21244, Germany
  • Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Neurology
    Buchholz in der Nordheide, 21244, Germany
  • Allgemeines Krankenhaus Celle, Neurology
    Celle, 29223, Germany
  • Carl-Thiem-Klinikum Cottbus gGmbH
    Cottbus, 03048, Germany
  • St. Vincenz Krankenhaus Datteln, Medizinische Klinik II, Cardiology
    Datteln, 45711, Germany
  • Klinikum Dortmund gGmbH,Stroke-Unit und Neurologische Intensivstation, Neurology
    Dortmund, 44137, Germany
  • LVR Klinikum Düsseldorf, Neurology
    Düsseldorf, 40629, Germany
  • Martin Gropius Krankenhaus, Klinik für Neurologie, Neurology
    Eberswalde, 16225, Germany
  • Universitätsklinikum Erlangen, Cardiology
    Erlangen, 91045, Germany
  • Alfried Krupp Krankenhaus Rüttenscheid, Neurology
    Essen, 45131, Germany
  • Contilia Herz- und Gefäßzentrum, Elisabeth-Krankenhaus Essen, Cardiology
    Essen, 45138, Germany
  • Kliniken an der Paar Friedberg Krankenhaus, Cardiology
    Friedberg, 86316, Germany
  • Herz-Thorax-Zentrum Fulda, Klinikum Fulda gAG, Universitätsmedizin Marburg - Campus Fulda, Cardiology
    Fulda, 36043, Germany
  • University of Giessen-Marburg, Neurology
    Giessen, D-35385, Germany
  • Universitätsmedizin Göttingen - Herzzentrum; Cardiology
    Göttingen, 37075, Germany
  • Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität, Neurology
    Greifswald, 17489, Germany
  • kbo-Isar-Amper-Klinikum München-Ost, Klinik für Neurologie, Neurology
    Haar, 85540, Germany
  • Martin-Luther-Universität, Universitätsklinik und Poliklinik für Neurologie, Neurology
    Halle, 06120, Germany
  • Universitätsklinik und Poliklinik für Innere Medizin III, Cardiology
    Halle, 06120, Germany
  • Asklepios Klinik St. Georg, Klinik für Neurologie
    Hamburg, 20099, Germany
  • Universitäres Herzzentrum Hamburg, Klinik für Allgemeine und Interventionelle Kardiologie, Universitätsklinikum Hamburg-Eppendorf, Cardiology
    Hamburg, 20246, Germany
  • Neurologie Neuer Wall, Fachärzte für Neurologie & Psychiatrie, Neurology
    Hamburg, 20354, Germany
  • Albertinen-Krankenhaus, Cardiology
    Hamburg, 22457, Germany
  • Asklepios Klinik Altona, Neurologische Abteilung mit überregionaler Stroke Unit, Neurophysiologie und Neurologischer Intensivmedizin
    Hamburg, 22763, Germany
  • Medizinische Hochschule Hannover, Klinik für Neurologie; Neurology
    Hanover, 30625, Germany
  • Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie und Pneumologie, Cardiology
    Heidelberg, 69120, Germany
  • Lausitzer Seenland Klinikum GmbH, Klinik für Neurologie, Neurology
    Hoyerswerda, 02977, Germany
  • Universitätsklinikum Jena, Neurology
    Jena, 07740, Germany
  • Universitätsklinikum Jena Klinik für Innere Medizin I
    Jena, 07747, Germany
  • DRK-Kliniken Nordhessen gGmbH , Klinik für Neurologie und Klinische Neurophysiologie, Neurology
    Kassel, 34121, Germany
  • Alexianer Krefeld GmbH, Krankenhaus Maria Hilf, Neurology
    Krefeld, 47805, Germany
  • Universitaetsklinikum Leipzig, Neurology
    Leipzig, 04103, Germany
  • Klinikum St. Georg gGmbH
    Leipzig, 04129, Germany
  • Asklepios Fachklinikum Lübben, Neurology
    Lubin, 15907, Germany
  • Universitäres Herzzentrum Lübeck, Medizinische Klinik II
    Lübeck, 23538, Germany
  • Sana Kliniken Lübeck GmbH, Medizinische Klinik II
    Lübeck, 23560, Germany
  • Universitätsklinikum Schleswig-Holstein
    Lübeck, 23562, Germany
  • DRK Schmerz-Zentrum, Neurology
    Mainz, 55131, Germany
  • Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurologie; Neurology
    Mainz, Germany
  • Diakonissen Speyer-Mannheim, Diakonissenkrankenhaus Mannheim, Neurology
    Mannheim, 68163, Germany
  • Neckar-Odenwald Kliniken gGmbH, Kreiskrankenhaus Mosbach, Kardiologie der Klinik für Innere Medizin
    Mosbach, 74821, Germany
  • Ökumenisches Hainich Klinikum gGmbH, Neurology
    Mühlhausen, 99974, Germany
  • Friedrich-Baur-Institut, Neurologische Klinik und Poliklinik, Neurology
    München, 80336, Germany
  • Kardiologie München Nord, Cardiology
    München, 80939, Germany
  • Ludwig-Maximilians-Universität München, Klinikum Großhadern, Neurologische Klinik und Poliklinik & Deutsches Schwindel- und Gleichgewichtszentrum DSGZ, Neurology
    München, 81377, Germany
  • Klinik und Poliklinik für Neurologie, Klinikum rechts der Isar, Technische Universität München
    München, 81675, Germany
  • Praxis für Neurologie, Neurology
    München, 81825, Germany
  • Ruppiner Kliniken GmbH,Hochschulklinikum der MHB, Neurology
    Neuruppin, 16816, Germany
  • UKRB Universitätsklinikum Ruppin Brandenburg
    Neuruppin, 16816, Germany
  • Kreiskrankenhaus Prignitz gGmbH, Neurology
    Perleberg, 19348, Germany
  • Krankenhaus Barmherzige Brüder Regensburg, Klinik für Neurologie, Neurology
    Regensburg, 93049, Germany
  • Universitätsklinikum Regensburg, Cardiology
    Regensburg, 93053, Germany
  • Nordwest-Krankenhaus Sanderbusch gGmbH, Neurologische Klinik, Neurology
    Sande, 26452, Germany
  • Sächsisches Krankenhaus Altscherbitz, Neurology
    Schkeuditz, 04435, Germany
  • Jung-Stilling Klinikum Siegen, Diakonie Westfalen Süd Neuro, Neurogeriatrie, Neurology
    Siegen, 57074, Germany
  • Elbe Klinikum Stade
    Stade, 21682, Germany
  • Asklepios Fachklinikum Teupitz, Neurology
    Teupitz, 15755, Germany
  • Universitätsklinikum Tübingen, Zentrum für Neurologie
    Tübingen, 72076, Germany
  • NeuroPoint, Neurology
    Ulm, 89073, Germany
  • University of Ulm, Neurology
    Ulm, 89081, Germany
  • Sophien-u.Hufeland-Klinikum, Klinik für Neurologie und Klinische Neurophysiologie, Neurology
    Weimar, 99425, Germany
  • Fachkrankenhaus Hubertusburg gGmbH, Neurologische Klinik, Neurology
    Wermsdorf, 04779, Germany
  • Sana HANSE Klinikum Wismar, Klinik für Neurologie, Neurology
    Wismar, 23966, Germany
  • Praxis für Neurologie, Neurology
    Wolfratshausen, v, Germany
  • Luzerner Kantonspital, Cardiology
    Lucerne, 6000, Switzerland
  • Solothurner Spitäler AG, Bürgerspital Solothurn, Cardiology
    Olten, 4500, Switzerland
  • Praxisgemeinschaft für Kardiologie, Innere Medizin und Psychosomatische Medizin, Cardiology
    Zug, 6300, Switzerland
07

Registry details

Key details

Study ID
NCT03237494
Lead sponsor
CENTOGENE GmbH Rostock
Collaborators
Alnylam Pharmaceuticals
Responsible party
Sponsor
First posted
Aug 2, 2017
Start date
Jul 20, 2017
Primary completion
May 16, 2025
Completion
May 16, 2025
Last update
Jun 29, 2025

Study contacts

Peter Bauer, Prof.
study chair · Centogene GmbH

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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