Back

TRAMmoniTTR  Study

In cooperation with Alnylam® Pharmaceuticals

The genetic screening of an at-risk population for hereditary TransthyRetin-related AMyloidosis and longitudinal monitoring of TTR positive subjects, the TRAMmoniTTR study, is a multicenter, observational, epidemiological, longitudinal study.

  1. Home
  2. Clinical Studies
  3. Global Patient Testing Programs
  4. Hereditary Transthyretin-Related Amyloidosis and Longitudinal Monitoring of TTR Positive Subjects (TRAMmoniTTR)

Summary and Rationale

Overview

The TRAMmoniTTR study aims to investigate the ATTRv prevalence in an at-risk population, monitor clinical status in TTR positive subject, and establish ATTRv biomarker(s).


Study access on CentoPortal® for participating physicians

CentoPortal®

Study Rationale

Hereditary Transthyretin Amyloidosis (ATTRv, hereditary amyloidosis, transthyretin-related) is an autosomal dominant condition caused by a pathogenic variant in the TTR gene (Plante-Bordeneuve et al. 2011). The TTR gene is coding for 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 proteins results in the transthyretin amyloidosis (ATTRv) diseases.

On average, the diagnosis is delayed by 4–5 years, especially in non-endemic areas. Also, potential misdiagnosis is due to ATTRv´s clinical heterogeneity (Adams et al., 2016).

In order to facilitate early diagnosis, treatment choice, and individualization, ATTRv biomarker(s) are crucial.

Patient Benefits

Participants will receive a definite diagnosis if a pathogenic variant in the TTR gene is found.

Information about the Study

Design: National, multicenter, epidemiological, observational, longitudinal study

Study population: Participants at risk for Hereditary Transthyretin Amyloidosis (ATTRv) and participants diagnosed with ATTRv

Number of patients: 5,000 participants

First patient in: November 2020

Last patient in: July 2022

Duration of study: 48 months

Objectives:

  • Monitoring of the clinical status in TTR positive subjects
  • Investigating the prevalence of ATTRv in an at-risk population
  • Establishing ATTRv biomarker(s)


Find out how you can participate: ClinicalTrials.gov

Study Design

The patients fulfilling the inclusion criteria will be enrolled in the study. All participants will have a single research blood sample drawn, which will be equivalent to 30 drops of blood (around 1ml). The sample will be applied to a CentoCard®, which will be sent to CENTOGENE and analyzed in CENTOGENE’s laboratory.

The sample will be genetically tested for ATTRv.

The TTR genetically positive subjects can participate further in the study.

First and second degree relatives of subjects with a class 1 (pathogenic), class 2 (likely pathogenic), or class 3 (variant of uncertain significance) variant in the TTR gene will be invited to the study site by a study doctor. The study doctor will check the clinical history of subjects. Symptomatic family members will be offered to be enrolled in the TRAMmoniTTR study, and the TTR gene will be genetically tested.

Asymptomatic family members will be offered genetic counseling prior to the predictive genetic testing for ATTRv.

QUARTERLY VISITSTIMEBLOOD COLLECTIONeCRF
V10 monthsyesyes
V23 monthsyesyes
V36 monthsyesyes
V49 monthsyesyes
V512 monthsyesyes
V615 monthsyesyes
V718 monthsyesyes
V821 monthsyesyes
V924 monthsyesyes

TRAM STUDY RESULTS PUBLICATION: ANNALS OF MEDICINE; 53:1, 1787-1796. PUBLISHED 2021 OCT 16.

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
The participant is at risk for ATTRv 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 ATTRv
  • Based on imaging or biopsy suspected for the wild type TTR (ATTR) and not genetically tested for ATTRv
OR
  • The participant is diagnosed with ATTRv
OR
  • The participant is a first or second degree relative of the TTR positive subject

Contact

Scientific Advisory Board (SAB)

PD Dr. Katrin Hahn (Chairwoman)
Universitätsmedizin Charité
10117  Berlin
Germany
Email: Katrin.Hahn(at)charite(dot)de

Prof. Dr. Birgit Aßmus
UKGM Giessen
35385 Giessen 
Germany
Email: birgit.assmus(at)innere.med.uni-giessen(dot)de

Prof. Dr. Thomas Skripuletz
Medizinische Hochschule Hannover
30625 Hannover
Germany
Email: Skripuletz.Thomas(at)mh-hannover(dot)de

Prof. Dr. Monika Patten-Hamel
UKE Hamburg
20246 Hamburg
Germany
Email: patten(at)uke(dot)de

Prof. Dr. Peter Bauer
CENTOGENE GmbH
Am Strande 7
18055 Rostock
Germany
Email: peter.bauer(at)centogene(dot)com

Project Team - CENTOGENE

Sabine Rösner
Clinical Project Manager
CENTOGENE GmbH
Am Strande 7
18055 Rostock
Germany
Email: sabine.roesner(at)centogene(dot)com

Dr. Xenia Bogdanovic
Clinical Study Researcher
CENTOGENE GmbH
Am Strande 7
18055 Rostock
Germany
Email: dr.xenia.bogdanovic(at)centogene(dot)com

Felix Reder
CPM Team Leader
CENTOGENE GmbH
Am Strande 7
18055 Rostock
Germany
Email: felix.reder(at)centogene(dot)com


Are you already enrolled in the study and want to log in to your CentoPortal® account?

CentoPortal®