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

June 25, 2025 updated by: CENTOGENE GmbH Rostock

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

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

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

5028

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Participants at risk for hATTR and participants diagnosed with hATTR
Participants 18 years of age or older

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analysis of prevalance of hATTR mutations among a cohort of participants at risk for hATTR.
Time Frame: 4 years
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
To monitor clinical status in TTR positive subjects.
Time Frame: 4 years
8 Follow up visits within 24 months
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Establishment of biomarker/s in TTR positive cohort.
Time Frame: 4 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CENTOGENE GmbH Rostock

Collaborators

Alnylam Pharmaceuticals

Investigators

  • Study Chair: Peter Bauer, Prof., CENTOGENE GmbH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2017

Primary Completion (Actual)

May 16, 2025

Study Completion (Actual)

May 16, 2025

Study Registration Dates

First Submitted

July 31, 2017

First Submitted That Met QC Criteria

July 31, 2017

First Posted (Actual)

August 2, 2017

Study Record Updates

Last Update Posted (Actual)

June 29, 2025

Last Update Submitted That Met QC Criteria

June 25, 2025

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRAM2 analysis

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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