View clinical trials related to Amyloidosis, Hereditary.
Filter by:The study design is a prospective registry including asymptomatic and symptomatic patients who carry a pathogenic TTR mutation. The study will enroll patients who meet the inclusion criteria and none of the exclusion criteria until 1000 patients are enrolled, at which point in time the study investigators will evaluate whether further patient accrual is meaningful.
ATTR amyloidosis is a rare and progressively disabling disease caused by the deposition of misfolded TTR protein in multiple tissues including the nerves, heart, and gastrointestinal tract. Polyneuropathy (PN) and cardiomyopathy (CM) are the two most frequent phenotypes and many patients presented a mixed picture of PN and CM. There are different methods to search for the existence and extent of PN and disability caused by ATTR amyloidosis (e.g. mNIS+7, Norfol, QoL-DN), these methods may not be sensitive enough to search for the onset of disease in patients carrying the pathogenic TTR variants or progression of PN in patients undergoing treatment. Also, some of the available methods can be difficult and time-consuming to perform. For this reason, there is a need for sensitive biomarkers that can aid in the investigation and follow-up of PN in patients with hATTR amyloidosis. NfL, a well-known biomarker of nerve damage due to both central and peripheral nervous system disorders, was recently evaluated as a potential biomarker of nerve damage in patients with hATTR amyloidosis. The results of this study can help understand the potential value of NfL in patients with PN of hATTR amyloidosis establishing i changes levels of this biomarker in response to different pathology-specific treatment options correlation between NfL levels and different ratings clinics. The primary objective of the study is to establish the potential of NfL as a biomarker of severity of polyneuropathy, progression and response to treatment in patients with symptomatic hATTR amyloidosis.
ATTRv amyloidosis is a systemic disease with two clinical forms, neurological and cardiological, which are sometimes combined (so-called mixed forms). Patisiran and vutrisiran have shown protective effects on the progression of neurological damage. The effects of Patisiran or vutrisiran on the heart remain incompletely understood. The aim of this study is to better understand the morphological and functional cardiac consequences in ATTRv patients with stage 1 or 2 polyneuropathy with a mixed form treated with Patisiran or vutrisiran
Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic specificity to detect early disease. The overall objectives of this study are to determine the presence of subclinical hATTR-CA and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The central hypothesis of this proposal is that hATTR-CA has a long latency period that will be detected through subclinical amyloidosis imaging and biomarker phenotyping. The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim 1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2) determine the association between amyloid-specific biomarkers and V122I TTR carrier status; and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim 1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-, and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our clinical sites. These biomarkers detect and quantify different processes of TTR amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers to detect imaging evidence of subclinical hATTR-CA disease.
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 program is to provide expanded access to Inotersen for up to 100 Patients with Hereditary Transthyretin Amyloidosis (hTTR).
The purpose of this study is to provide expanded access of patisiran to patients with hereditary transthyretin-mediated amyloidosis (hATTR).
The purpose of this study was to evaluate the safety and efficacy of revusiran (ALN-TTRSC) in patients with transthyretin (TTR) mediated Familial Amyloidotic Cardiomyopathy. Dosing has been discontinued; patients are being followed-up for safety.
The purpose of this study is to evaluate the safety and efficacy of patisiran (ALN-TTR02) in patients with transthyretin (TTR) mediated amyloidosis. An open-label, single-arm, long-term follow-up extension study NCT02510261 (ALN-TTR02-006) was initiated to provide participants who completed this study with continued patisiran-LNP (lipid nanoparticle) treatment.