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

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ClinicalTrials.gov Identifier: NCT03237494
Recruitment Status : Recruiting
First Posted : August 2, 2017
Last Update Posted : April 22, 2021
Sponsor:
Collaborator:
Alnylam Pharmaceuticals
Information provided by (Responsible Party):
CENTOGENE GmbH Rostock

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

Condition or disease
Transthyretin Amyloidosis Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy Polyneuropathies Cardiomyopathies

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.

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Study Type : Observational
Estimated Enrollment : 5000 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : July 20, 2017
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024


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



Primary Outcome Measures :
  1. 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.

  2. To monitor clinical status in TTR positive subjects. [ Time Frame: 4 years ]
    8 Follow up visits within 24 months


Secondary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Participants at risk for Hereditary Transthyretin Amyloidosis (hATTR) and participants diagnosed with hATTR
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03237494


Contacts
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Contact: Sabine Roesner +49 381 80113657 sabine.roesner@centogene.com

Locations
Show Show 76 study locations
Sponsors and Collaborators
CENTOGENE GmbH Rostock
Alnylam Pharmaceuticals
Investigators
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Study Chair: Peter Bauer, Prof. Centogene GmbH
Additional Information:
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Responsible Party: CENTOGENE GmbH Rostock
ClinicalTrials.gov Identifier: NCT03237494    
Other Study ID Numbers: TRAM2 analysis
First Posted: August 2, 2017    Key Record Dates
Last Update Posted: April 22, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CENTOGENE GmbH Rostock:
Peripheral Nervous System Diseases
Transthyretin Amyloidosis
Transthyretin-related familial amyloid polyneuropathy
Transthyretin-related familial amyloid cardiomyopathy
Additional relevant MeSH terms:
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Polyneuropathies
Amyloid Neuropathies, Familial
Amyloid Neuropathies
Cardiomyopathies
Amyloidosis
Heart Diseases
Cardiovascular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors