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Screening for the Transthyretin-Related Familial Amyloidotic Small Fiber Polyneuropathy (TRAP2)

This study is currently recruiting participants.
Verified May 2017 by Prof. Dr. Arndt Rolfs, University of Rostock
Sponsor:
ClinicalTrials.gov Identifier:
NCT01705626
First Posted: October 12, 2012
Last Update Posted: May 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Centogene AG Rostock
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
  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, vitamin B12, RF, ANA, antibodies against Lyme borrelia) 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 Small Fiber Polyneuropathy - a International, Multicentre, Epidemiological Protocol

Resource links provided by NLM:


Further study details as provided by Prof. Dr. Arndt Rolfs, 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.

Estimated Enrollment: 500
Study Start Date: December 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts
Observation
all adult patients at 18 years with small fiber polyneuropathy of undetermined etiology based on the normal results of laboratory data (CRP, glucose, electrolytes, urea, transaminases, TSH, immunoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia ; no anamnesis for carcinoma, no continuous alcohol consumption; no light-chain-amyloidosis; no anamnesis for heavy metal exposure

Detailed Description:

Neuropathies are generalised disorders of the peripheral nervous system, due to deranged function of the peripheral motor, sensory and autonomic neurons, their fibres or their myelin sheath. Dysfunction of unmyelinated C and myelinated Aδ fibres causes symptoms like insensitivity or hypersensitivity to heat and/or cold and neuropathic pain. These fibres have slow conduction velocities, carrying temperature feeling and pain sensations from nociceptors and thermoreceptors respectively. An isolated disturbance of these fibres leads usually to the diagnosis of small fibre neuropathy (SFN). The pathogenesis of SFN 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 genetic polyneuropathy may be a hereditary amyloidosis. These have been described as endemic in Sweden, Portugal or Japan. 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 (Ando et al., 2005; Adams et al., 2010). This study focuses on TTR-FAP (OMIM: #105210, OMIM: *176300), 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 (Orphanet, ORPHA 85447). 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 destabilised as in TTR-FAP.

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
adult Patients with small fiber polyneuropathy of undetermined etiology based on: the normal results of laboratory data (CRP, glucose, electrolytes, urea,transaminases, TSH, immunoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia)
Criteria

Inclusion Criteria:

  • Informed consent will be obtained from the patient before any study related procedures
  • Patients aged older than 18 years
  • Patients with small fiber polyneuropathy of undetermined etiology based on:the normal results of laboratory data (CRP, glucose, electrolytes, urea,transaminases, TSH, immunoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia)
  • No anamnesis for carcinoma
  • No continuous alcohol consumption
  • No light-chain-amyloidosis
  • No anamnesis for heavy metal exposure
  • Progressive idiopathic small fiber polyneuropathy
  • Presence of an electrophysiological examination for N. Peroneus and N. Suralis

Exclusion Criteria:

  • No Informed Consent from the patient before any study related procedures
  • Patients younger than 18 years
  • The etiology of the small fiber polyneuropathy is already known based on:
  • significant pathological results for any of the following laboratory data (CRP, glucose, electrolytes, urea, transaminases, TSH, immunoglobulins, vitamin B12, RF, ANA, antibodies against Lyme borrelia)
  • Positive anamnesis for carcinoma
  • Continuous alcohol consumption
  • Light-chain-amyloidosis
  • Anamnesis for heavy metal exposure
  • No progression of idiopathic small fiber polyneuropathy within the last two years
  • No presence of an electrophysiological examination for N. Peroneus and N. Suralis
  Contacts and Locations
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): NCT01705626


Contacts
Contact: Arndt Rolfs, MD 49-381-494 ext 9540 arndt.rolfs@med.uni-rostock.de
Contact: Sabine Roesner 49-381-494 ext 4749 sabine.roesner@med.uni-rostock.de

Locations
Germany
Albrecht-Kossel-Institute for Neuroregeneration (AKos) Centre for Mental Health Disease University of Rostock Recruiting
Rostock, Germany, 18147
Contact: Arndt Rolfs, Prof.    +49 381 494 ext 9540    arndt.rolfs@med.uni-rostock.de   
Contact: Sabine Roesner    +49 381 494 ext 4749    sabine.roesner@med.uni-rostock.de   
Sponsors and Collaborators
University of Rostock
Centogene AG Rostock
Investigators
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

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
First Submitted: October 9, 2012
First Posted: October 12, 2012
Last Update Posted: May 11, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Prof. Dr. Arndt Rolfs, University of Rostock:
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn

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