27 Clinical Trials for Various Conditions
This study evaluates the safety and tolerability of extended dosing with IONIS-TTR Rx in patients with Familial Amyloid Polyneuropathy.
The purpose of this study is to evaluate the efficacy and safety of inotersen given for 65 weeks in participants with Familial Amyloid Polyneuropathy (FAP).
This study will examine whether Fx-1006A is effective in halting the progression of Familial Amyloid Polyneuropathy (FAP). Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP. The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience. This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.
The purpose of this study is to determine if diflunisal can prevent progressive lower leg nerve damage in patients with familial amyloidosis polyneuropathy. Funding Source - FDA Office of Orphan Products Development (OOPD); National Institute of Neurological Disorders and Stroke (NINDS)
See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)
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 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.
The MaesTTRo study aims to enroll a global cohort of patients with transthyretin (ATTR) amyloidosis to longitudinally observe the natural course of the disease and describe real-world treatment patterns and outcomes. In addition, information on the effectiveness of ATTR amyloidosis treatments, including eplontersen, which is a ligand-conjugated antisense oligonucleotide gene silencing treatment targeting activity against both the mutant and wild-type TTR protein, will be collected.
The purpose of the study is to evaluate and compare different tools that are used to detect evidence of peripheral neuropathy in patients with TTRv.
The purpose of this study is to collect and evaluate pregnancy outcomes, pregnancy complications, and fetal/neonatal/infant outcomes in women exposed to patisiran-LNP.
The purpose of this study is to: * Describe epidemiological and clinical characteristics, natural history and real-world clinical management of ATTR amyloidosis patients * Characterize the safety and effectiveness of patisiran and vutrisiran as part of routine clinical practice in the real-world clinical setting * Describe disease emergence/progression in pre-symptomatic carriers of a known disease-causing transthyretin (TTR) variant
To evaluate the effectiveness of patisiran in patients with ATTRv amyloidosis with polyneuropathy who have a V122I or T60A mutation.
This study will evaluate the efficacy and safety of vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) compared to placebo in patients with ATTR amyloidosis with cardiomyopathy.
Transthyretin is a protein produced in the liver that transports thyroid hormone and vitamin A. A single substitution of an amino acid in the structure of TTR can result in a relatively unstable protein, the breakdown products of which (predominantly monomers) aggregate abnormally and produce proteinaceous deposits in nerves and the heart. These deposits are known as amyloid and produce progressive nerve and heart damage. Amyloidosis due to a mutant TTR is usually an autosomal dominant and hence is a familial condition. Wild-type TTR is also capable of producing amyloid deposits which predominantly involves the heart (rather than the nervous system) resulting in a progressive decrease in cardiac function with increasing signs of heart failure. This study aims to determine whether subcutaneous injection of an antisense oligonucleotide drug, known as inotersen, that has been specifically designed to reduce production of the protein transthyretin by the liver, can slow or stop the progression of TTR amyloid cardiomyopathy as compared to historical controls, using advanced echocardiography and cardiac MRI. The study also aims to determine the tolerability and safety of this drug when administered over a 24-month period to patients with TTR amyloid cardiomyopathy.
The purpose of this study is to evaluate the safety and efficacy of long-term dosing with ALN-TTR02 (patisiran) in participants with transthyretin (TTR) mediated amyloidosis (ATTR).
The objective of the study is to determine whether the combination of the bile acid TUDCA, and doxycycline will slow the progression of familial and senile amyloidosis.
The tetracycline antibiotic doxycycline disrupts A beta amyloid fibrils (AB) in Alzheimer's disease, transthyretin (ATTR) amyloid fibrils in familial amyloidotic polyneuropathy, and immunoglobulin light chain (AL) amyloid fibrils in transgenic mouse models of disease. If untreated, amyloid deposits impair organ function, affecting the morbidity and mortality of patients. This single-center, twelve-month, open-label, prospective, pilot phase II study aims to determine whether doxycycline reduces amyloid deposits and improves organ function in patients with systemic or localized amyloidosis. The investigators plan to enroll patients with measurable amyloid disease according to internationally-accepted diagnostic criteria. Patients must have stable organ function at enrollment. Eligible subjects not receiving active treatments for amyloidosis affecting their kidneys, heart, aerodigestive tracts, peripheral or autonomic nervous system(s), lungs, eyes, skin, bladder, or breasts will undergo evaluations at baseline, 6 months, and 12 months - or more frequently as clinically indicated. Over 45 years experience indicates doxycycline is a safe, well tolerated antibiotic. The investigators will use standard grading systems to assess doxycycline response following twelve months of treatment.
This study measures circulating, misfolded ATTR oligomers in asymptomatic ATTRm amyloidosis genetic carriers longitudinally over five years.
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 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.
This is an open label study to treat dominantly inherited Alzheimer's disease (DIAD) mutation carrier participants from the DIAN-TU-001 gantenerumab Open Label Extension (OLE) period with lecanemab to determine the effects of amyloid removal on age of onset and clinical progression compared to external controls, if amyloid plaque as measured by amyloid PET can be fully removed in DIAD, and the effects of amyloid removal on biomarkers of disease progression.
The purpose of this study is to determine if intensive lowering of systolic blood pressure (SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high risk for memory decline or dementia.
This prospective, randomized, multicenter, double-blind, parallel group, placebo-controlled, dose-ranging study will evaluate the safety, tolerability, PK (Pharmacokinetic) and PD (Pharmacodynamic) of AG10 compared to placebo administered on a background of stable heart failure therapy. Screening and randomization will be followed by a 28-day blinded, placebo-controlled treatment period.
The purpose of this study is to characterize the frequency of TTR mutations in subjects suspected of having cardiac amyloidosis
The main objective of this study is to evaluate the safety and efficacy of NC-503 compared to placebo in patients with secondary (AA) amyloidosis using a composite assessment of clinical improvement/worsening of both renal and gastrointestinal functions.
Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits (amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. Gamma waves are important for memory, and in patients with AD, there are fewer gamma waves in the brain. The Tsai lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. A light and sound device was developed for humans that stimulates the brain at 40Hz that can be used safely at home. The goal of this study is to see if using this device can prevent dementia in people who are at risk for developing Alzheimer's disease.
The purpose of this study is to determine if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease prevention in African Americans, who are at high risk for Alzheimer's disease.