Hereditary Transthyretin-Related Amyloidosis and Longitudinal Monitoring of TTR Positive Subjects (TRAMmoniTTR)
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.
Summary
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).
Hereditary Transthyretin Amyloidosis is an autosomal dominant condition caused by a pathogenic variant in the TTR gene (Plante-Bordeneuve et al. 2011), also known as ATTRv (hereditary amyloidosis transthyretin variant). The TTR gene is coding for transthyretin protein (Ttr), formerly known as prealbumin. Transthyretin is found primarily in the serum (secreted by the liver) and cerebrospinal fluid (secreted by the choroid plexus), and functions as a carrier, *trans*port for the hormone *thyr*oxine (T4) and *retin*ol-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 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).
Patient Benefits
Participants will receive a definite diagnosis if a pathogenic variant in the TTR gene is found.
Clinical Trials
Study access on CentoPortal® for participating physicians
Study Rationale & Design
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.
Study Design
The patients fulfilling the inclusion criteria will be enrolled into 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 molecular genetically tested with NGS-based sequencing of the entire TTR gene.
| QUARTERLY VISITS | TIME | BLOOD COLLECTION | eCRF |
|---|---|---|---|
| V1 | 0 months | yes | yes |
| V2 | 3 months | yes | yes |
| V3 | 6 months | yes | yes |
| V4 | 9 months | yes | yes |
| V5 | 12 months | yes | yes |
| V6 | 15 months | yes | yes |
| V7 | 18 months | yes | yes |
| V8 | 21 months | yes | yes |
| V9 | 24 months | yes | yes |
TRAM STUDY RESULTS PUBLICATION: ANNALS OF MEDICINE; 53:1, 1787-1796. PUBLISHED 2021 OCT 16.
Information About the Study
Design: Epidemiological, multicenter, international, and non-interventional study
Study population: Participants at risk for Hereditary Transthyretin Amyloidosis (hATTR) and participants diagnosed with hATTR
Number of patients: 5,000 participants
First patient in: April 2018
End of study: April 2024
Objectives:
- To monitor clinical status in TTR positive subjects
- To investigate the hATTR prevalence in an at-risk population
- To establish hATTR biomarker/s
Find out how you can participate: ClinicalTrials.gov
Inclusion 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 |
The participant is at risk for ATTRv due to two or more the factors listed below:
|
Resources
Quick Links
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Contact TRAMmoniTTR Study
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