Amyloidosis

Researchers are evaluating the use of 18FFT8, a diagnostic imaging agent, for detecting amyloidosis, including cardiac amyloidosis. This study aims to assess the safety and effectiveness of 18FFT8 PETCT 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 18FFT8, followed by a PETCT 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 PETCT scan. Researchers will monitor safety from the time of injection up to seven days afterward, and evaluate organ uptake and biodistribution of 18FFT8 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 a new imaging technique using 64CuFBP8, a novel fibrin-binding PET probe combined with simultaneous cardiac PETMRI, 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 the imaging can identify clots in over 90% of patients who have confirmed clots based on a standard transesophageal echocardiogram TEE. Secondary analyses will explore how these clots relate to heart function and amyloid build-up in the left ventricle. Participants will receive an injection of 64CuFBP8 followed by simultaneous cardiac PETMR imaging. The study involves twenty individuals with documented cardiac amyloidosis and atrial fibrillation or flutter. The imaging is performed once, and results will be compared to recent or upcoming TEE tests to confirm the presence of clots. This study focuses on evaluating the diagnostic value of this new PETMRI method in detecting intracardiac thrombi. During the study, participants will undergo PETMR imaging after receiving the tracer injection. The main outcome measured is the detection of intracardiac thrombus within one day of imaging. The researchers will also assess associations between clots and heart function or amyloid burden. Participants will be monitored for eligibility and safety, including assessments of their ability to undergo imaging and recent heart evaluations. The study is expected to last from July 2026 to March 2027, with diagnostic imaging as the key procedure.

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 diseases 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 evaluating 99mTc-p514, a synthetic peptide labeled with technetium-99m, as a radiotracer for detecting amyloid deposits in patients with AL or ATTR systemic amyloidosis, particularly those with heart involvement. This phase 1 study aims to assess how the tracer distributes in the body and the radiation dose it delivers compared to healthy volunteers. The study builds on previous findings showing that the peptide binds to amyloid and clears quickly from the bloodstream, potentially allowing detailed imaging of affected tissues using specialized scans. Participants include healthy volunteers and patients diagnosed with systemic amyloidosis. They will receive a single intravenous dose of 99mTc-p514, followed by a series of imaging scans planar scintigraphy and SPECTCT at various time points up to 24 hours post-injection. Patients will also undergo a comparison imaging procedure using 99mTc-Pyrophosphate to evaluate heart amyloid deposits. Blood samples, vital signs, ECGs, and echocardiograms will be collected at specified times during the study. Throughout the approximately 8-day study period, participants will have multiple imaging sessions and clinical assessments to monitor tracer distribution and radiation exposure. The main measurement is whole body effective dosimetry. Researchers will also measure tracer uptake in the heart and other tissues. Safety monitoring includes vital signs and heart function tests. The study involves a brief outpatient schedule with imaging and blood sampling to support diagnosis improvement for systemic amyloidosis.

Researchers are evaluating AZD0120, a CAR T cell therapy targeting CD19 and B Cell Maturation Antigen BCMA, in participants with relapsed or refractory light chain AL amyloidosis. This open-label Phase 1b2 study aims to assess the safety, tolerability, and efficacy of AZD0120 in this patient group. Participants must have a confirmed diagnosis of AL amyloidosis affecting one or more organs and measurable hematologic disease. Participants will receive a weight-based dose of AZD0120 administered by intravenous infusion. The study includes a single treatment group where all participants receive the investigational drug. The trial is designed to monitor the impact of AZD0120 on participants with relapsed or refractory AL amyloidosis following at least one prior anti-plasma cell therapy. During the study, participants will undergo assessments to monitor treatment-emergent adverse events and hematologic response, including complete response rates. Blood levels of AZD0120 will also be measured over time. Follow-up will continue for a minimum of six months to evaluate safety and efficacy outcomes. Participants are expected to attend scheduled study visits and comply with protocol requirements throughout the trial duration.

Researchers are evaluating the effects of ALN-APP on disease progression in adults with sporadic Cerebral Amyloid Angiopathy sCAA and Dutch-type Cerebral Amyloid Angiopathy D-CAA. This Phase 2 study aims to assess the safety, tolerability, and pharmacodynamics of ALN-APP in these patient groups. The study is sponsored by Alnylam Pharmaceuticals and includes a randomized, double-blind, placebo-controlled 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 an optional 18-month open-label extension will receive ALN-APP. The study involves two main periods the initial double-blind treatment phase followed by an optional open-label extension. During the study, participants will undergo brain MRIs to measure new cerebral microbleeds and other brain changes. Researchers will also assess cerebrovascular vasoreactivity using functional MRI and measure amyloid precursor protein levels in cerebrospinal fluid. Safety and adverse events will be monitored throughout the up to 50 months of participation, which includes screening, treatment, and safety follow-up.