Amyloidosis

Researchers are evaluating the use of [18F]FT8, a diagnostic imaging agent, for detecting amyloidosis, including cardiac amyloidosis. This study aims to assess the safety and effectiveness of [18F]FT8 PET/CT scans in visualizing AL amyloid deposits in the heart, comparing its performance to established clinical methods such as echocardiography, MRI, and laboratory tests. The goal is to establish a reliable PET imaging protocol for direct diagnosis and differentiation of AL amyloidosis. Participants will receive a single intravenous injection of 10 b1 3 mCi of [18F]FT8, followed by a PET/CT scan to measure organ uptake using the standardized uptake value (SUV). The study includes both healthy volunteers and amyloidosis patients. The imaging and injection occur only once, and no additional treatments are administered. Clinical assessments and lab tests are done before and after the scan to monitor safety and gather diagnostic information. During the study, participants will undergo physical exams, cardiac function assessments, and tests of liver and kidney function before and after the PET/CT scan. Researchers will monitor safety from the time of injection up to seven days afterward, and evaluate organ uptake and biodistribution of [18F]FT8 at the time of the scan. Radiation exposure is also measured. Total participation involves a single visit for imaging and assessments, with follow-up safety monitoring over one week.

Researchers are evaluating the ability of [64Cu]FBP8, a new fibrin-binding PET imaging probe, to detect intracardiac blood clots in people with transthyretin or light chain cardiac amyloidosis who also have atrial fibrillation or atrial flutter. This pilot study aims to see if [64Cu]FBP8 PET combined with cardiac MRI can identify clots in over 90% of patients confirmed to have intracardiac thrombi by transesophageal echocardiogram (TEE). The study also explores links between clots and heart function and amyloid burden. Participants will receive an injection of [64Cu]FBP8 followed by simultaneous cardiac PET/MR imaging to detect intracardiac thrombi. This imaging approach is compared against TEE results as a reference standard. The study involves twenty individuals with documented cardiac amyloidosis and atrial fibrillation or flutter undergoing this imaging procedure. During the trial, participants will have cardiac PET/MRI scans after tracer injection, with data collected to evaluate the presence of thrombi. The primary outcome is the detection of intracardiac thrombus within one day of imaging. Researchers will also assess heart function and amyloid levels. Safety and ability to complete the imaging procedure will be monitored. Participants' involvement includes consent, undergoing imaging, and review of recent TEE results over the study period.

Researchers are evaluating a new 10-minute cardiovascular magnetic resonance (CMR) imaging protocol designed to improve current CMR procedures for patients with various heart conditions, including coronary artery disease, cardiomyopathies, and other cardiac diseases. The study aims to develop a standardized, contrast-free imaging method that can be applied to about 70% of cardiac patients. The goal is to assess whether this shorter protocol enhances diagnostic decision-making and reduces healthcare costs. The study involves two groups: healthy volunteers over 18 years old without significant cardiovascular or respiratory conditions, and patients over 18 years who require a clinically indicated CMR exam. The new protocol focuses on heart function and tissue characterization without using contrast agents. Researchers will compare the new 10-minute protocol to standard CMR imaging, evaluating its clinical feasibility, performance, and cost-effectiveness in different patient populations. Participants will undergo CMR scans using both the new and standard protocols. Researchers will monitor diagnostic results, scan completion rates, scan sequence times, adverse events, and cost differences between methods. Various heart tissue measurements and reproducibility between different readers and scanners will also be assessed. The study spans from 2019 to 2025, with ongoing safety monitoring during imaging sequences and a focus on improving the efficiency and quality of cardiac imaging.

Researchers are establishing a prospective group of patients with plasma cell disorders (PCDs) to better understand these conditions and their treatments. This study focuses on various PCDs including multiple myeloma, amyloidosis, and other related disorders. It aims to explore how minimal residual disease (MRD) status relates to patient prognosis and investigate the role of the tumor microenvironment (TME) in the disease's development and progression. Patients with confirmed PCDs who are hospitalized and willing to participate will be followed over time. Biological samples such as peripheral blood, bone marrow aspirate, and urine will be collected before and after treatment to support future research. The study does not involve any intervention and participants will be regularly assessed at baseline, then at 1, 3, 6, and 12 months after treatment, followed by yearly visits. During the study, clinical and laboratory data along with biological samples will be gathered to analyze disease features and treatment responses. Follow-up visits will monitor patient progress and outcomes for up to ten years. The main outcome is to maintain a comprehensive cohort and understand the relationship between MRD and prognosis in PCD patients, while also supporting further studies on tumor clone evolution and disease mechanisms.

Researchers are establishing a European registry and sample sharing network called EUREKA to collect new cases of AL amyloidosis from referral centers and their satellite sites across Europe. This observational study aims to use advanced molecular technologies and big data analysis, including artificial intelligence, to better understand the disease mechanisms, improve early diagnosis, and guide treatment decisions. The study also seeks to describe the natural history of AL amyloidosis in patients receiving modern anti-plasma cell therapies and to refine methods for detecting minimal residual disease after treatment. The study involves creating a biorepository and sample sharing network to study disease-causing light chains and plasma cells using cutting-edge molecular techniques. A dedicated site will support the consortium with big data and AI applied to health data. Participants will be followed over time at participating centers, with data collected to assess outcomes such as mortality and hematologic relapse in those achieving complete response to therapy. Participants will be involved through regular follow-up visits at their treatment centers, with collection of clinical data and biological samples. Researchers will monitor outcomes including mortality at 24 months after diagnosis and rates of relapse in patients with minimal residual disease. The study duration allows for long-term observation to better understand disease progression and response to treatment in a real-world setting.

Cardiac amyloidosis (CA) involves amyloid deposits in the heart, mainly caused by immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). This study focuses on patients in Taiwan, where the common ATTR mutation A97S is linked to left ventricular hypertrophy. Early diagnosis and proper treatment are crucial for better outcomes. The trial aims to improve diagnosis and prognosis by analyzing clinical and imaging data, using artificial intelligence to develop predictive models from 99mTc-PYP scans. Participants suspected or diagnosed with CA will undergo Tc-99m PYP cardiac scans to detect amyloid deposits. The study collects retrospective and prospective data from multiple medical centers in Taiwan, including imaging quality assessments and visual grading by nuclear medicine physicians. Genetic testing and blood and urine tests for AL amyloidosis will be performed when indicated. Follow-up for at least one year will monitor outcomes. Participants will provide clinical data and undergo imaging assessments, including PYP scans graded for amyloid uptake. Researchers will analyze these along with genetic and laboratory tests to build diagnostic and prognostic models. The primary outcome is death within one year, with secondary outcomes including cardiovascular death and hospitalization for heart failure. This observational study helps gather real-world evidence to guide clinical decisions and patient care over the study period.

This research aims to better understand mitral and tricuspid valve leakage (regurgitation) in patients diagnosed with transthyretin amyloid cardiomyopathy (ATTR-CM). It focuses on measuring how common these valve problems are, their severity, and how they affect patient outcomes. The study also seeks to create new standards for grading this leakage that fit the unique heart function changes seen in ATTR-CM, improving on current methods that do not account for this specific condition. As an observational study, it will gather detailed heart ultrasound (echocardiographic) data from patients with ATTR-CM, focusing on quantitative and semi-quantitative measures of mitral and tricuspid regurgitation. There are no experimental treatments; instead, the study collects information to better define and predict the impact of valve leakage in this condition. The research is conducted internationally across multiple centers, starting in 2025. Participants will undergo comprehensive baseline heart ultrasound assessments within about six months of diagnosis and then be followed for up to 60 months. Researchers will track outcomes including all-cause death, cardiovascular death, and hospitalizations due to heart failure. The study involves regular clinical follow-up and data collection to analyze the relationship between valve leakage measures and patient prognosis under typical care conditions.

Researchers are studying AZD0120, a CAR T cell therapy targeting CD19 and BCMA, in people with relapsed or refractory light chain (AL) amyloidosis. This phase 1b/2 open-label study aims to evaluate the safety, tolerability, and effectiveness of AZD0120 in this patient group. The trial is sponsored by Alexion Pharmaceuticals, Inc. and focuses on participants who have measurable hematologic disease and prior therapy experience. Participants will receive a weight-based dose of AZD0120 through an intravenous infusion. The study includes both phase 1b and phase 2 periods. During these phases, researchers will monitor treatment-emergent adverse events and assess the proportion of participants achieving a complete response or hematologic response. The treatment is given once, and participants will be closely observed throughout the study. Throughout the study, participants will have regular visits for safety assessments, laboratory tests, and blood level monitoring of AZD0120. The primary outcomes include tracking adverse events in phase 1b and measuring complete response rates in phase 2, both over at least six months. Secondary outcomes include monitoring AZD0120 levels in the blood and hematologic response rates. Participants will be monitored closely for a minimum of six months following treatment to evaluate treatment effects and safety.

Researchers are evaluating the effects of ALN-APP on cerebral amyloid angiopathy (CAA), a condition affecting blood vessels in the brain. This study focuses on adult patients with sporadic CAA and Dutch-type CAA to understand how ALN-APP influences disease progression, safety, tolerability, and pharmacodynamics. The trial is sponsored by Alnylam Pharmaceuticals and involves a Phase 2 clinical trial design. Participants will receive multiple doses of ALN-APP or placebo administered intrathecally during a 24-month double-blind treatment period. Those who continue into the optional open-label extension period of 18 months will receive ALN-APP. The study includes two main periods: the initial double-blind phase and the optional open-label extension. During the study, participants will undergo brain MRI scans to measure new cerebral microbleeds, hemorrhagic events, and other disease markers over 24 months. Researchers will also assess cerebrovascular reactivity and concentrations of amyloid precursor proteins in cerebrospinal fluid. Safety will be monitored through adverse event tracking up to 48 months. Total participation, including screening and follow-up, may last up to 50 months.

Researchers are studying the safety and effectiveness of a single dose of nexiguran ziclumeran (NTLA-2001) compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score +7 (mNIS+7) over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants' nerve health and overall well-being.