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Sponsored by: |
FoldRx Pharmaceuticals |
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Information provided by: | FoldRx Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT00628745 |
THAOS is a global, multi-center, longitudinal observational survey open to all patients with transthyretin-associated amyloidoses (ATTR), including ATTR-PN (polyneuropathy), ATTR-CM (cardiomyopathy) and wild-type ATTR-CM. It is open-ended with a minimum duration of 10 years. Patients will be followed as long as they are able to participate.
The principal aims of this outcome survey are to better understand and characterize the natural history of the disease by studying a large and heterogenous patient population. Survey data may be used to develop new treatment guidelines and recommendations, and to inform and educate clinicians about the management of this disease.
Condition | Intervention |
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TTR-Associated Amyloidosis |
Other: THAOS is a noninterventional patient registry |
Study Type: | Observational |
Study Design: | Prospective |
Official Title: | Transthyretin-Associated Amyloidoses Outcomes Survey (THAOS) A Global, Multi-Center, Longitudinal, Observational Survey of Patients With Documented Transthyretin (TTR) Mutations or Wild-Type TTR Amyloidosis |
Samples for TTR genotyping and DNA analysis may be collected.
Estimated Enrollment: | 1000 |
Study Start Date: | December 2007 |
Transthyretin (TTR) a 127-amino acid, tetrameric protein, primarily synthesized in the liver, is a secreted protein present in the blood and cerebrospinal fluid and is a carrier of thyroxine and retinol-binding protein-retinol (vitamin A) complex. Transthyretin-associated amyloidoses (ATTR) are diseases caused by dissociation of the transthyretin tetramer into monomers, which misfold, ultimately forming amyloid deposits in various organs. This structural instability of the TTR tetramer can occur due to genetic mutations of the gene encoding the TTR protein, or can be associated with aging. There are over 80 known mutations of TTR, which result in variable phenotypic expressions of amyloidosis that commonly affect the peripheral nerves, heart, kidney or vitreous.
ATTR with polyneuropathy (ATTR-PN) occurs when amyloid predominantly affects the peripheral and autonomic nerves. V30M (substitution of methionine for valine at position 30) is the most common mutation associated with this disease. The age of onset can be in the third or fourth decade of life or later, depending on the mutation carried and the patient's ethnic background. The main feature of ATTR-PN is progressive sensorimotor and autonomic neuropathy. Sensory neuropathy typically starts in the lower extremities followed by motor neuropathy within a few years. Autonomic neuropathy quite often accompanies the sensory and motor deficits. The lifespan for patients is severely shortened, with death occurring within 9-11 years from the first symptoms. The only demonstrated disease-modifying therapy for ATTR-PN is orthotopic liver transplantation.
ATTR with cardiomyopathy (ATTR-CM) occurs when the heart is predominantly affected. In this disease, also known as familial amyloid cardiomyopathy (FAC), amyloid fibrils infiltrate the myocardium, leading to diastolic dysfunction progressing to restrictive cardiomyopathy. ATTR-CM is late-onset with symptoms typically occurring in patients over 60 years old. One common mutation, V122I (substitution of isoleucine for valine at position 122), occurs with high frequency (prevalence of 3.9%) in African-Americans. The natural history of ATTR-CM is not well defined. In the elderly, wild-type (normal) transthyretin may become structurally unstable resulting in deposition of amyloid fibrils primarily in heart tissue and leading to restrictive cardiomyopathy and heart failure. Combined heart and liver transplantation is a current treatment option, however limited organ availability and significant patient co-morbidity limit transplant as a treatment option.
Various compounds have been shown to stabilize the TTR tetramer in vitro and in vivo, thus preventing TTR dissociation into monomers and formation of amyloid fibrils. Whether these TTR stabilizing compounds can positively impact disease progression is being evaluated in clinical trials in patients with TTR-associated amyloidosis. FoldRx Pharmaceuticals, Inc. is developing an investigational drug, Fx-1006A, as a novel, specific stabilizer of transthyretin for the treatment of TTR-associated amyloidosis.
The objectives of this survey are:
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
Patients with a documented genotyped TTR mutation, with or without a diagnosis of TTR-associated amyloidosis, or patients with wild-type TTR-associated amyloidosis with cardiomyopathy.
Inclusion Criteria:
Patient has confirmed:
Confirmation of wild-type ATTR-CM will be determined by one of the following set of criteria (A or B):
A. Presence of amyloid in cardiac biopsy tissue confirmed as TTR amyloid by immunohistochemistry and genotyped confirmation that patient does not possess a known mutation in TTR gene (i.e., is a carrier of wild-type allele only) via genetic testing; or B. Evidence of cardiac involvement by echocardiogram as defined by mean left ventricle wall thickness of > 12 mm, and presence of amyloid in non-cardiac tissue confirmed as TTR amyloid by immunohistochemistry, and genotyped confirmation that patient does not possess a known mutation in TTR gene (i.e., is a carrier of wild-type allele only) via genetic testing.
Exclusion Criteria:
United States, California | |
Stanford University School of Medicine, Falk Cardiovascular Research Center | Recruiting |
Stanford, California, United States, 94305 | |
Contact: Ronald Witteles, MD 650-723-6141 | |
Principal Investigator: Ronald Witteles, MD | |
United States, Colorado | |
University of Colorado, Hospital Neurosciences Center | Recruiting |
Denver, Colorado, United States, 80010 | |
Contact: Diana Quan, MD 303-315-7221 | |
Principal Investigator: Diana Quan, MD | |
United States, Illinois | |
Northwestern University Feinberg School of Medicine, Division of Cardiology, Department of Medicine | Recruiting |
Chicago, Illinois, United States, 60208 | |
Contact: Sanjiv Shah, MD 312-695-1105 sanjiv.shah@northwestern.edu | |
Principal Investigator: Sanjiv Shah, MD | |
United States, Maryland | |
Johns Hopkins Hospital | Recruiting |
Baltimore, Maryland, United States, 21205 | |
Contact: David Cornblath, MD 410-955-2229 dcornbl@jhmi.edu | |
Principal Investigator: David Cornblath, MD | |
University of Maryland - Division of Cardiology | Recruiting |
Baltimore, Maryland, United States, 21201-1595 | |
Contact: Stephen S Gottlieb, MD 410-328-8788 sgottlie@medicine.umaryland.edu | |
Principal Investigator: Stephen S Gottlieb, MD | |
United States, Massachusetts | |
Harvard Vanguard Medical Associates, Central Medical Specialities | Not yet recruiting |
Boston, Massachusetts, United States, 02215-3904 | |
Contact: Rodney Falk, MD 617-421-6050 | |
Principal Investigator: Rodney Falk, MD | |
United States, New York | |
Columbia University Medical Center, Ceneter for Advanced Cardiac Care, Presbyterian Hospital | Recruiting |
New York, New York, United States, 10032 | |
Contact: Matthew Maurer, MD Msm10@columbia.edu | |
Principal Investigator: Matthew Mauer, MD | |
United States, Oregon | |
Neuromuscular Diseases Center, Oregon Health and Science University | Recruiting |
Portland, Oregon, United States, 97239-3098 | |
Contact: Edward J Culper, MD 503-494-7772 | |
Principal Investigator: Edward J Culper, MD | |
Argentina | |
FLENI Departamento de Hepatología y Transplante de Organos | Not yet recruiting |
Buenos Aires, Argentina | |
Contact: Pedro Trigo, MD +54-11-48267094 pltrigo@yahoo.com.ar | |
Principal Investigator: Pedro Trigo, MD | |
Brazil | |
Hospital Universitario Clementino Fraga Filho | Recruiting |
Rio de Janeiro, Brazil | |
Contact: Marcia Waddington-Cruz, MD marwaddi@centroin.com.br | |
Principal Investigator: Marcia Waddington-Cruz, MD | |
Cyprus | |
Neuropathology Lab Cyprus Institute of Neurology and Genetics | Not yet recruiting |
Nikosia, Cyprus | |
Contact: Theodore Kyriakides, MB, ChB, BSc +357 22 358 600 theodore@cing.ac.cy | |
Principal Investigator: Theodore Kyriakides, MB, ChB, BSc | |
Denmark | |
Dept of Cardiology B Åarhus University Hospital, Skejby | Not yet recruiting |
Arhus, Denmark | |
Contact: Henning Molgaard, MD 45 8949 6113 h.molgaard@dadlnet.dk | |
Principal Investigator: Henning Molgaard, MD | |
France | |
Service de Neurologie, CHU Henri Mondor | Not yet recruiting |
Paris, France | |
Contact: Violaine Plante-Bordeneuve, MD +33-1-45-21-26-18 vplante@free.fr | |
Principal Investigator: Violaine Plante-Bordeneuve, MD | |
Portugal | |
Unidade Clinica de Paramiloidose, Hospital Geral de Santo Antonio, Largo Prof Abdel Salazar | Recruiting |
Porto, Portugal | |
Contact: Teresa Coelho, MD +351-22-207-7500 ext 1318 or 1284 tcoelho@netcabo.pt | |
Principal Investigator: Teresa Coelho, MD | |
Servicio de Neurologica Piso 7, Hospital de Santa Maria | Recruiting |
Lisbon, Portugal | |
Contact: Isabel Conceicao, MD +351-21-7805219 isabel.conceicao@armail.pt | |
Principal Investigator: Isabel Conceicao, MD | |
Spain | |
Hospital Clinic Villarroel | Recruiting |
Barcelona, Spain | |
Contact: Josep Campistol, MD JMCAMPIS@clinic.ub.es | |
Principal Investigator: Josep Campistol, MD | |
Sweden | |
FAP-Teamet Familjar Amyloids, Norrlands universitetssjukhus | Recruiting |
Umea, Sweden | |
Contact: Ole B Suhr, MD +46-90-785-1383 ole.suhr@medicin.umu.se | |
Principal Investigator: Ole B Suhr, MD |
Responsible Party: | FoldRx Pharmaceuticals, Inc. ( Barbara White (bwhite@foldrx.com, 617-252-5534) ) |
Study ID Numbers: | Fx-R-001 |
Study First Received: | February 25, 2008 |
Last Updated: | January 6, 2009 |
ClinicalTrials.gov Identifier: | NCT00628745 |
Health Authority: | United States: Institutional Review Board |
TTR Transthryetin ATTR |
ATTR with polyneuropathy ATTR with cardiomyopathy wild type TTR |
Amyloidosis Metabolic Diseases Polyneuropathies Metabolic disorder Cardiomyopathies |