Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01705626
First received: October 9, 2012
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to determine the prevalence of patients with a polyneuropathy of undetermined etiology based on the normal results of laboratory data (CRP, glucose, electrolytes, urea, transaminases, TSH, immunoglobulins, cryoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia, HIV, anti-GM1 antibodies) and CSF; no anamnesis for carcinoma, no continuous alcohol consumption; no light-chain-amyloidosis; no anamnesis for heavy metal exposure.


Condition
Polyneuropathies
Amyloidosis
Amyloid Neuropathies
Amyloidosis, Familial
Metabolic Diseases

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: TTR-FAP Screening - Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy - a National, Multicentre, Epidemiological Protocol

Resource links provided by NLM:


Further study details as provided by University of Rostock:

Biospecimen Retention:   Samples With DNA

For the molecular genetic diagnosis of the disease TTR-FAP a sequencing of the entire TTR gene in all study patients will be performed. Dried blood spots will be used for this procedure.


Enrollment: 550
Study Start Date: January 2013
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Observation
all adult patients at 18 years with a polyneuropathy of undetermined etiology based on the normal results of laboratory data (CRP, glucose, electrolytes, urea, transaminases, TSH, immunoglobulins, cryoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia, HIV, anti-GM1 antibodies) and CSF; no anamnesis for carcinoma, no continuous alcohol consumption; no light-chain-amyloidosis; no anamnesis for heavy metal exposure

Detailed Description:

Diseases of diverse etiology can be correlated to the term polyneuropathy(PNP). The pathogenesis may be of inflammatory, autoimmune, metabolic, toxic or hereditary nature. Careful clinical and electrodiagnostic assessment, with attention to the pattern of involvement and the types of nerve fibers most affected, narrows the differential diagnosis and helps to focus the laboratory evaluation. Beside the frequent genetic etiologies in PNP (pmp22, MFN2) one cause of a polyneuropathy may be a hereditary amyloidosis. This term describes the accumulation of misfolded protein in the interstitial space. The abnormal accumulation of β-fibrils can be detected histologically by Congo pink staining. Aside from acquired amyloidotic neuropathies (e.g. PNP caused by AL-amyloidosis [AL=amyloidosis with light chain immunoglobins]) there are also hereditary amyloidotic neuropathies.These have been described as endemic in Sweden, Portugal or Japan. More recent studies provided evidence for the presence of hereditary amyloidotic neuropathies amongst the German population and that they are currently underdiagnosed. The most common form of the hereditary familial amyloidotic neuropathy (FAP) is the Transthyretin-related FAP, however two other amyloidogenic proteins have been described: Apolipoprotein A-I and Gelsolin.

This study focuses on TTR-FAP, whose prevalence shall be determined in a cohort of 500 patients with polyneuropathy of unknown etiology. The TTR-FAP is an autosomal dominant disease, the exact prevalence of which is unknown but estimated to be around 1:100,000 to 1:1,000,000 in the normal population.By limiting the study population to patients with PNP of unknown etiology it should be possible to gain evidence for the prevalence of the disease in Germany by investigating fewer patients.

While the diagnosis of the amyloidotic neuropathy can be conducted histologically, a molecular genetic approach is necessary to diagnose TTR-FAP. Even though more than 100 point mutations are known to cause the disease, the most common amino acid change is V30M.The mutation in the TTR gene causes the destabilization of the physiologically tetrameric protein. Usually transthyretin consists of four identical monomeric subunits and binds the thyroxin circulating in the blood plasma. The monomeric subunits exhibit a pronounced β-sheet structure which leads to the accumulation of unsoluble β-fibrils when they are destabilized as in TTR-FAP.This accumulation of misfolded TTR can lead to three phenotypes known as-cardiac TTR amyloidosis,

- leptomeningeal TTR amyloidosis and the TTR-FAP.The TTR-FAP has a very heterogeneous phenotype which can manifest starting at the age of 18 and may lead to death within 10 years. The symptoms can be categorized in three groups

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

adult Patients with a polyneuropathy of undetermined etiology based on the normal results of laboratory data (CRP, glucose, electrolytes, urea, transaminases, TSH, immunoglobulins, cryoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia, HIV, anti-GM1 antibodies) and CSF; no anamnesis for carcinoma, no continuous alcohol consumption; no light-chain-amyloidosis; no anamnesis for heavy metal exposure

Criteria

Inclusion Criteria:

  • Informed consent will be obtained from the patient before any study related procedures
  • Patients with a polyneuropathy of undetermined etiology based on the normal results of laboratory data (CRP, glucose, electrolytes, urea, transaminases, TSH, immunoglobulins, cryoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia, HIV, anti-GM1 antibodies) and CSF; no anamnesis for carcinoma, no continuous alcohol consumption; no light-chain-amyloidosis; no anamnesis for heavy metal exposure
  • Patients older than 18 years of age
  • Progressive idiopathic polyneuropathy

Exclusion Criteria:

  • No Informed consent from the patient before any study related procedures
  • Patients younger than 18 years of age
  • The etiology of the polyneuropathy is already known based on the pathological results of laboratory data (CRP, glucose, electrolytes, urea, transaminases, TSH, immunoglobulins, cryoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia, HIV, anti-GM1 antibodies) and pathological CSF; anamnesis for carcinoma, continuous alcohol consumption or light-chain-amyloidosis or anamnesis for heavy metal exposure
  • No progression within the last two years
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01705626

Locations
Austria
Universität Innsbruck, Neuologische Klinik
Innsbruck, Austria, 6020
Germany
Universitätsklinikum der RWTH Aachen
Aachen, Germany, 52074
Klinikum Altenburger Land GmbH, Klinik für Neurologie
Altenburg, Germany, 04600
Fachklinik für Physikalisch Medizin und Medizinische Rehabilitation, Buchberg-Klinik
Bad Tölz, Germany, 83646
Krankenhaus Hohe Warte, Klinik für Neurologie
Bayreuth, Germany, 95445
Kliniken Beelitz GmbH, Neurologische Reha-Kliniken
Beelitz, Germany, 14547
Vivantes Netzwerk, Auguste Viktoria Klinikum, Klinik für Neurologie
Berlin, Germany, 12157
Jüdisches Krankenhaus Berlin, Klinik für Neurologie
Berlin, Germany, 13347
St. Josef Hospital, Universitätsklinik Bochum, Klinik für Neurologie
Bochum, Germany, 44791
MVZ Dreiländereck
Boizenburg, Germany, 19258
Allgemeines Krankenhaus Celle
Celle, Germany, 29223
Klinikum Dachau, Neurologisches u. Schlafmedizinisches Zentrum
Dachau, Germany, 85221
Bezirksklinikum Mainkofen, Klinik für Neurologie
Deggendorf, Germany, 94469
Städtisches Klinikum Dessau, Klinik für Neurologie mit klinischer Neurophysiologie
Dessau, Germany, 06847
Klinikzentrum Mitte, Neurologische Klinik
Dortmund, Germany, 44137
Martin Gropius Krankenhaus, Klinik für Neurologie
Eberswalde, Germany, 16225
Alfried Krupp Krankenhaus, Rüttenscheid, Klinik für Neurologie
Essen, Germany, 45131
Universitätsklinikum Essen, Neurologische Klinik
Essen, Germany, 45147
Universitätsmedizin Greifswald, Klinik und Poliklinik für Neurologie
Greifswald, Germany, 17475
Städtisches Klinikum Görlitz gGmbH, Neurologische Klinik
Görlitz, Germany, 02828
KMG Klinikum Güstrow GmbH, Klinik für Neurologie
Güstrow, Germany, 18273
Krankenhaus Martha-Maria Halle-Dölau gGmbH, Akademisches Lehrkrankenhaus der Martin-Luther-Universität Halle
Halle, Germany, 06120
Universitätsklinikum Hamburg-Eppendorf, Kopf-u.Neurozentrum, Klinik für Neurologie,
Hamburg, Germany, 20251
Universitätsklinikum Jena, Klinikum für Neurologie
Jena, Germany, 07747
KliUniversitätsklinikum Leipzig - AöR, Klinik und Poliklinik für Neurologie
Leipzig, Germany, 04103
DRK-Schmerz-Zentrum Mainz
Mainz, Germany, 55127
Neurologische Klinik am Johannes-Wesling-Klinikum Minden
Minden, Germany, 32429
Hainich Klinikum Mühlhausen
Mühlhausen, Germany, 99974
Dietrich Bonhoeffer Klinikum, Klinik für Neurologie
Neubrandenburg, Germany, 17036
Neurologische Klinik Ruppiner Kliniken GmbH
Neuruppin, Germany, 16816
Kreiskrankenhaus Prignitz, Klinik für Neurologie
Perleberg, Germany, 19348
St. Josefs-Krankenhaus Potsdam
Potsdam, Germany, 14471
Arztpraxis für Neurologie und Psychiatrie
Ribnitz Damgarten, Germany
University of Rostock, Albrecht Kossel Institute
Rostock, Germany, 18147
Klinikum Saarbrücken, Neurologische Klinik
Saarbrücken, Germany, 66119
Kreiskrankenhaus Sigmaringen, Klinik fürNeurologie
Sigmaringen, Germany, 72488
Asklepios Fachklinik Brandenburg
Teupitz, Germany, 15755
St. Johannes Krankenhaus
Troisdorf-Sieglar, Germany, 53844
NeuroPoint
Ulm, Germany, 89073
Arztpraxis für Neurologie Neue Mitte
Ulm, Germany, 89073
Universitätsklinikum Ulm, Klinik für Neurologie
Ulm, Germany, 89081
Sophien-u.Hufeland-Klinikum Klinik für Neurologie und Klinische Neurophysiologie
Weimar, Germany, 99425
Fachkrankenhaus Hubertusburg, Klinik für Neurologie
Wermsdorf, Germany, 04779
Sponsors and Collaborators
University of Rostock
Pfizer
Investigators
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier: NCT01705626     History of Changes
Other Study ID Numbers: TRAP 08-2012
Study First Received: October 9, 2012
Last Updated: February 4, 2014
Health Authority: Germany: Ethics Commission

Keywords provided by University of Rostock:
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn

Additional relevant MeSH terms:
Amyloidosis
Metabolic Diseases
Polyneuropathies
Amyloid Neuropathies
Amyloidosis, Familial
Proteostasis Deficiencies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on April 23, 2014