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Amyloidosis clinical trials

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NCT ID: NCT04611204 Terminated - Clinical trials for Carpal Tunnel Syndrome

Transthyretin Cardiac Amyloidosis in Patients With Idiopathic Carpal Tunnel Syndrome Referred for Release Surgery

PRATHYC
Start date: October 1, 2020
Phase:
Study type: Observational

This study will determine the prevalence of transthyretin amyloidosis in pathology of the transverse carpal ligament and cardiac involvement using natriuretic peptides, electrocardiography and echocardiography in patients referred for carpal tunnel release surgery of idiopathic carpal tunnel syndrome. This study will describe the relationship between amyloid deposition observed on the transverse carpal ligament and the presence of cardiac involvement.

NCT ID: NCT04424914 Terminated - Clinical trials for Heart Failure With Preserved Ejection Fraction

Global Prevalence of ATTR-CM in Participants With HFpEF

Start date: December 30, 2020
Phase: N/A
Study type: Interventional

This study is a global, multi-center study designed to estimate the global prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) within a clinically at risk population [participants with heart failure with preserved ejection fraction (HFpEF)].

NCT ID: NCT04115956 Terminated - AL Amyloidosis Clinical Trials

A Clinical Study of Melphalan Flufenamide (Melflufen) and Dexamethasone for Patients With Immunoglobulin Light Chain (AL) Amyloidosis

Start date: August 6, 2020
Phase: Phase 1
Study type: Interventional

This is a phase 1/2 open label study of melphalan flufenamide (melflufen) in combination with dexamethasone for participants with Al amyloidosis following at least one prior line of therapy. Melflufen will be administered on Day 1 of each 28-day cycle in combination with dexamethasone on days 1 and 2. In both phases, treatment of each individual participant will continue for up to 8 cycles or until any stopping events occur. Approximately 46 participants will be enrolled. The study was intended to be a Phase 1/2 trial but was early terminated and never moved forward to Phase 2.

NCT ID: NCT03879278 Terminated - Amyloidosis Clinical Trials

Multiple Ascending Dose Study in Healthy Subjects

Start date: March 6, 2019
Phase: Phase 1
Study type: Interventional

This will be a Phase 1, randomized, double-blind, single center, placebo-controlled, multiple ascending dose (MAD) study in a maximum of 3 cohorts of 8 healthy male and female subjects each. Subjects in Cohorts 1, 2 and 3 will receive ascending multiple IV doses of NPT189 or matching placebo.

NCT ID: NCT03774784 Terminated - Amyloidosis Clinical Trials

A Study of the Natural History of Leukocyte Chemotactic Factor 2 Amyloidosis (ALECT2) Disease

Start date: January 29, 2019
Phase:
Study type: Observational

The purpose of this study is to characterize the natural history of leukocyte chemotactic factor 2 amyloidotic (ALECT2) disease. In this observational study participants with ALECT2 disease will be enrolled. Participants, who have already reached end-stage renal disease (ESRD), will provide retrospective chart review data and biological specimens at baseline only. Other participants, in addition to retrospective chart review, will be followed prospectively.

NCT ID: NCT03474458 Terminated - Clinical trials for Cardiac AL Amyloidosis

A Trial of Doxycycline vs. Standard Supportive Therapy in Newly-diagnosed Cardiac AL Amyloidosis Patients Undergoing Bortezomib-based Therapy

Start date: February 11, 2019
Phase: Phase 2/Phase 3
Study type: Interventional

Systemic amyloidoses are rare diseases affecting approximately 1 in 100,000 persons each year. In systemic amyloidoses abnormal proteins deposit in bodily organs and severely impair their function, causing death if not treated effectively. Light chain (AL) amyloidosis is caused by a usually small population of plasma cells (the cells that produce antibodies). These cells produce part of antibodies, the light chains (LC) that form amyloid deposits. Almost every organ, with the exception of the brain, can be affected by AL amyloidosis. The heart is involved in three fourths of patients and is responsible for almost all the deaths occurring in the first 6 months after diagnosis. Current therapy of AL amyloidosis is based on drugs targeting the plasma cells producing the amyloid-forming LC. At present, most patients receive a powerful anti-plasma cell drug, bortezomib, as part of their initial treatment. However, bortezomib-based therapy, can improve heart involvement only in less than one third of patients with AL amyloidosis, and many patients (approximately one third) still die within 12 months from diagnosis. Early cardiac deaths remain an acute unmet need and the major determinant of overall outcome in this disease. Thus, there is the need of alternative means to treat heart involvement in AL amyloidosis. Doxycycline is a widely used, well tolerated, antibiotic that has been marketed for decades and used to treat a number of different infectious diseases caused by bacteria. This molecule has been extensively studied in the laboratory, in animal models and, more recently, in small studies involving patients, for its potential of improving cardiac damage in amyloidosis. These studies showed that doxycycline disrupts amyloid deposits, reduces the amyloid load in a mouse model, and counteracts the toxicity exerted by amyloid-forming LCs on C. elegans, a worm whose pharynx is used as a model resembling human heart. In a small clinical study, doxycycline was given to patients with cardiac AL amyloidosis during treatment for their underlying plasma cell disease. This resulted in a remarkable improvement of survival compared to "matched historical controls" (i.e. similar patients who had received only anti-plasma cell therapy without doxycycline in the past). Based on these promising preliminary results, we designed the present clinical trial to assess whether the addition of doxycycline to anti-plasma cell therapy can improve survival in patients with cardiac AL amyloidosis who were not previously treated. The rate of survival at 12 months will be compared in patients receiving doxycycline and in controls receiving standard antibiotic therapy, together with anti-plasma cell therapy. Patients will be assessed for parameters of plasma cell disease, heart involvement and possible involvement of other organs, as well as for quality of life. To make sure that patients who will receive doxycycline and those who will not have comparable severity of cardiac disease, patients will be stratified according to the stage of cardiac involvement. Patients with very advanced heart dysfunction will not be enrolled in the trial, because preliminary data indicate that doxycycline is of little or no benefit in these subjects. Patients will be randomized to receive doxycycline or standard antibiotics in combination with anti-plasma cell therapy. Bortezomib-based treatment directed against plasma cells will be delivered according to each participating institutions' guidelines. Doxycycline will be administered at a dosage of 100 mg two times a day, which is usual in the treatment of bacterial diseases. Standard antibiotics will be delivered according to each participating institutions' guidelines (provided that drugs of the same class as doxycycline are not administered) in the control arm. Patients will be provided a diary to record possible adverse events and will be instructed accordingly. Patients will be evaluated at trial centers every 2 months for treatment efficacy and toxicity. In case of unsatisfactory response second-line therapy will be initiated. In the absence of unacceptable toxicity, doxycycline administration will be continued for the entire duration of follow-up (12 months).

NCT ID: NCT03417830 Terminated - Amyloidosis Clinical Trials

Biodistribution of 89Zirconium-labelled GSK2398852 Using PET Imaging

Start date: April 6, 2018
Phase: Phase 1
Study type: Interventional

The principal aim of this study is to investigate the cardiac uptake of 89Zr-GSK2398852 in subjects with transthyretin cardiomyopathy amyloidosis (ATTR-CM), and its biodistribution to other organs. Low doses of GSK2398852 will be co-administered at levels not high enough for therapeutic benefit. This study will be conducted in two parts: Part A and Part B. Subjects in Part A will participate in up to two dosing sessions and subjects in Part B will participate in one dosing session. Subjects will undergo up to 3 PET scans at varying intervals after 89Zr-GSK2398852 administration. The total duration of study will be approximately 3 to 4 months for subjects in Part A and approximately 2 months for subjects in Part B. Part B of the study will be triggered based on data obtained in Part A and other emerging data.

NCT ID: NCT03336580 Terminated - Clinical trials for Amyloidogenic Transthyretin (ATTR) Amyloidosis

A Study of PRX004 in Subjects With Amyloid Transthyretin (ATTR) Amyloidosis

Start date: April 5, 2018
Phase: Phase 1
Study type: Interventional

A Phase 1, open-label study of intravenous (IV) PRX004 as a single agent in subjects with hereditary amyloid transthyretin (hATTR) amyloidosis. The study will consist of 3 phases and will enroll up to a total of 36 subjects. A 3+3 dose escalation component to determine the safety, tolerability, PK, PD, and MTD. An expansion component in anticipated PRX004 RP2D cohorts selected from the Dose Escalation Phase. An extended dosing component for eligible subjects from the Dose Escalation or Expansion phases.

NCT ID: NCT03333551 Terminated - Cardiac Amyloidosis Clinical Trials

Cardiac Uptake of 18F Florbetapir in Patients Undergoing Chemotherapy

Start date: October 1, 2020
Phase: Phase 4
Study type: Interventional

This is a pilot study designed to assess for relative change in cardiac 18F Florbetapir uptake in patients with AL cardiac amyloidosis after appropriate chemotherapy.

NCT ID: NCT03328338 Terminated - Cardiac Amyloidosis Clinical Trials

Mitochondrial Function in Transthyretin Amyloidosis

MIT-Amylose
Start date: July 17, 2018
Phase:
Study type: Observational

Hereditary (familial) amyloidosis arising from the misfolding of a mutated or variant transthyretin, is the most frequent form of amyloid cardiomyopathy in the Caribbean basin. Affected organs invariably harbor extracellular amyloid deposits in the myocardium. Circulating or pre-fibrillar amyloidogenic proteins are implicated in the disruption of cell function. The investigators aim is to demonstrate that transthyretin mediated amyloid disease alter the mitochondrial function of cardiac cells.