View clinical trials related to Transthyretin Amyloidosis.
Filter by:Phase 3 efficacy and safety study to evaluate acoramidis (AG10) HCl 800 mg administered orally twice a day compared to placebo in subjects with symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM).
The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02) in participants with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will receive vutrisiran subcutaneous (SC) injection once every 3 months (q3M) or the reference comparator patisiran intravenous (IV) injection once every 3 weeks (q3w) during the 18 month Treatment Period. This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints during the 18 Month Treatment Period. Following the 18 Month Treatment Period, all participants will be randomized to receive vutrisiran SC injection once every 6 months (q6M) or q3M in the Randomized Treatment Extension (RTE) Period.
The purpose of this study is to determine whether Tolcapone crosses from the blood stream into the fluid around the brain and stabilizes the protein that makes leptomeningeal amyloid. Tolcapone is a commercially available generic drug that treats Parkinson's disease. The Investigator plans to evaluate Tolcapone as a treatment for ATTR (Transthyretin Amyloidosis), a rare genetic disease often causing death within 5-15 years after diagnosis. ATTR is characterized by deposition of misfolded protein known as amyloid, in one or more organ systems (including the peripheral and autonomic nervous systems, the heart, the brain and the eyes). The age at which symptoms begin to develop varies widely ranging between 20 to 70 years old. ATTR is progressive, and some variants can have a fatal outcome within a few years of presentation. Treatment options include supportive and symptomatic care that may slow or stop progressive decline in functional state but do not alter the pathological process. Liver transplant can be performed in selected patients but is limited by organ supply, requires lifelong immunosuppression, and may be complicated by progressive heart and nerve amyloid deposition. Importantly, liver transplant does not alter the natural course of central nervous system amyloid disease. To date, no treatment for ATTR penetrates the CNS. At present there is no FDA approved treatment for ATTR amyloidosis in the US. In Europe, Tafamidis has been approved for treatment of stage 1 ATTR-polyneuropathy since 2012. Tafamidis and Tolcapone bind to the thyroxine binding site of TTR (with different drug-transthyretin interactions) and in so doing stabilizes the tetrameric form of TTR, preventing dissociation and amyloid fibril formation The preclinical and clinical data from a variety of experimental systems support the therapeutic activity of TOLCAPONE in TTR mediated disease.
Familial amyloid neuropathies (FAP) are hereditary disease due to a mutation of the tranthyretin gene (TTR). These neuropathies are severe and life frightening. Asymptomatic carrier of TTR mutation are now detected in large TTR-FAP family. However, it is very hard to detect the moment where a TTR mutation carrier become symptomatic: too early diagnosis exposes the patients to side effect of the treatment and too late diagnosis exposes the patient to disease progression and clinical sequels. Neurological monitoring comprises clinical examination, electrophysiology and imaging. Sensitivity and specificity of these tools are not sufficient and we have to develop new biomarkers sensitive enough to detect modifications under treatment and the moment where a TTR mutation carrier become symptomatic Magnetic resonance imaging (MRI) can well evaluate neuromuscular diseases. Electrophysiological examination is also a good tool to evaluate NAF. MUNIX is a technique that permits to estimate the number of motor unit in one muscl. MUNIX is related to the disability in chronic inflammatory neuropathies and could be more sensitive than clinical scales and other electrophysiological data to detect modification of the disease in TTR-FAP. The objective of this exploratory study is to test the applicability of MUNIX and MRI as early measures for detecting the transition from asymptomatic to symptomatic TTR-FAP. In symptomatic TTR-FAP we will determine if MUNIX and MRI data are related to clinical deficiency and disability of the patients. This is a transversal exploratory study. If we manage to demonstrate that MRI and MUNIX can segregate symptomatic versus asymptomatic TTR mutation gene carriers, we will propose a longitudinal study with a follow up of more asymptomatic gene carriers.
This study measures circulating, misfolded ATTR oligomers in asymptomatic ATTRm amyloidosis genetic carriers longitudinally over five years.
Aortic stenosis is the most common valve disease requiring surgery in the Western world. It is defined by progressive calcification and fibrosis of the valve leaflets and restricted valve opening. This in turn exposes the heart muscle (left ventricle) to increasing pressure leading to heart muscle thickening (left ventricular hypertrophy, LVH) to normalise wall stress and maintain heart output (stroke volume). The only treatment available is relief of pressure overload by surgical or minimally invasive valve replacement (TAVI). Transthyretin (TTR) amyloidosis is a condition characterised by deposition of insoluble transthyretin protein (a small protein tetramer produced in the liver) in various tissues, predominantly in the heart. Although there are inherited forms caused by specific TTR gene mutations, most cases occur in older individuals with non-mutated TTR (wild-type). The finding of TTR plaques in elderly individuals is relatively common; in a post-mortem study 22-25% of patients over the age of 80 had evidence of cardiac amyloid deposition. However, there is significant progressive amyloid accumulation in a small percentage of individuals leading to heart muscle thickening and heart failure. No medical treatments are currently licensed although several agents are at advanced stages of clinical trials. As both the above conditions are increasingly common in the elderly population and characterised by increased heart muscle thickening, there is the potential for them to coexist unrecognised in individual patients. The prevalence of cardiac amyloidosis in clinical populations with significant aortic stenosis is not known however small series have estimated somewhere in the region of 6-29%. Other data have suggested that patients with aortic stenosis and concurrent cardiac amyloidosis have an adverse prognosis even despite AVR. It is therefore important to identify aortic stenosis patients with coexistent amyloidosis both in terms of predicting prognosis and because it may influence decisions about whether to proceed to valve intervention. PET/MR is an emerging technique, which combines the excellent temporal and spatial resolution of MRI with the sensitive molecular imaging of PET. PET/MR has significant advantages over PET/CT (the currently more widely used approach) in that it offers superior tissue characterisation, improved correction for cardiac and respiratory motion and major reductions in radiation exposure. Whilst there are concerns about its ability to provide reliable attenuation correction of the PET data, these issues appear to have been largely overcome with recent techniques proposed by our group. MR is also more naturally suited to the imaging of certain tissues in the body compared to CT including the left ventricular myocardium. In aortic stenosis, MRI has become the gold-standard technique for examining the heart muscle (myocardium) with the unique ability to assess its tissue composition. In particular both late gadolinium enhancement (LGE) and T1 mapping based techniques are able to detect heart scarring (fibrosis) which act as biomarkers of left ventricular decompensation and are strongly associated with poor patient outcomes. CMR is also the gold-standard non-invasive technique for detecting cardiac amyloid, which is associated with both a characteristic pattern of LGE and high native T1 values. However it is not currently able to differentiate between the two different types of cardiac amyloid TTR and AL amyloidosis, which have different prognoses and treatments. Preliminary studies conducted by our group have suggested that 18F-NaF PET when added to CMR can make this distinction on the basis that this tracer binds to TTR deposits but not AL deposits, may be able to differentiate between the two. Importantly we have also used the same PET tracer as a marker of calcification activity in the aortic valve, demonstrating its ability to predict disease progression and cardiac events. In this study, we will investigate whether PET/MR could be used as "one-stop" imaging in aortic stenosis in whom valve intervention is being considered to assess in detail functional and structural properties of both the valve and myocardium and identify cases of significant cardiac TTR amyloid deposition.
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
Familial amyloid neuropathy due to transthyretin gene mutations (TTR-FAP) is a rare autosomal dominant inherited disease resulting in the abnormal multi-system deposition of amyloid proteins. These deposits produce a multi-organ disease. AP is usually fatal 10 to 15 years after onset of symptoms if untreated. The prevalence of the disease remains still poorly understood and usually the search for this pathology is done in a third line of investigation. So the average time to diagnosis is extremely long, from 12 to 24 month. Now that the investigators have etiological treatment ( famidis (Vyndaqel®) and Diflunisal (Dolobid)) of this disease, it is essential to be able to detect FAP patients as early as possible. With this study, investigator decided to test for TTR mutation all patients presented with neuropathy of unknown etiology at the first line of investigation. The goal of this study is to evaluate the prevalence of FAP-TTR among neuropathy and defined the best strategy to test this population for TTR mutations.
The investigators will prospectively evaluate tissue samples obtained from patients undergoing carpal tunnel release surgery for amyloid in the soft tissue that is removed. Patients who have tissue that stains positive for amyloid will undergo cardiac testing to look for evidence of cardiac involvement.
International, multicenter, observational, longitudinal study to identify biomarker/s for the development of a new MS-based biomarker for the early and sensitive diagnosis of Transthyretin-Related Familial Amyloidotic Polyneuropathy from blood and number of correctly identified patients with Transthyretin-Related Familial Amyloidotic Polyneuropathy