A Follow-Up Study to Monitor Therapeutic Response in Transthyretin Cardiac Amyloidosis Using Amyloid Reactive Peptide 124I-evuzamitide (AT01) PET/CT
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Median of Uptake of Evuzamitide as Measured by Volume of Interest in Milliliters
研究概览
简要总结
This was a single center, prospective cohort study that is evaluating the ability of 124I-evuzamitide PET scanning to detect potential therapeutic changes in subjects under treatment for ATTR after one year had elapsed since their original 124I-evuzamitide PET scan.
Ten previously scanned subjects re-consented to undergo another 124I-evuzamitide PET scan. Demographic, clinical and phenotypic data were collected to characterize potential changes since their previous scans.
详细描述
Transthyretin cardiac amyloidosis (ATTR-CA) causes progressive heart disease that is often overlooked. It harms the heart muscle because the unstable, unfurled amyloid proteins fold up into large pieces that get caught in between layers of heart tissue, causing amyloid deposits. The earlier it is detected, the better for the patient.
There is a need to improve the early diagnosis of this disease because echocardiography (sonograms of the heart) and cardiac MRI are not useful enough for this. There is an X-ray of the heart using a compound called PYP that can detect amyloid deposits earlier than ultrasound images or clinical signs, but it's not clear how early it does so. Also, it can't detect amyloid deposits outside the heart, which causes lots of pain and suffering in people with this disease.
In the first phase of this study the radiation compound, evuzamitide, was shown to detect amyloidosis in the heart of selected subjects. So, the investigators used it to detect potential therapeutic changes in 10 subjects undergoing treatment for Transthyretin Amyloidosis.
Changes in the uptake of evuzamitide were compared between subjects treated on stabilizer only, subjects treated on silencer only and subjects treated with two different combinations of stabilizer plus silencer
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 105 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
- •Were enrolled in the initial pilot using 124I-Evuzamitide, on ATTR stabilizer and/or silencer therapy. Able to understand and sign the informed consent document after the nature of the study has been fully explained.
- •TTR genotype shown to be either Val122Ile or wild type.
排除标准
- •Overall Inclusion Criteria:
- •Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
- •Were enrolled in the initial pilot using 124I-Evuzamitide, on ATTR stabilizer and/or silencer therapy. Able to understand and sign the informed consent document after the nature of the study has been fully explained.
- •TTR genotype shown to be either Val122Ile or wild type.
- •The presence of any of the following excludes eligibility for enrollment in this study:
- •Primary amyloidosis (AL) or secondary amyloidosis (AA).
- •Active malignancy or non-amyloid disease with expected survival of less than 1 year.
- •Heart failure, in the opinion of the investigator, primarily caused by something other than amyloidosis.
- •Ventricular assist device.
- •Impairment from stroke, injury or other medical disorder that precludes participation in the study.
- •Disabling dementia or other mental or behavioral disease.
- •Enrollment in a clinical trial not approved for co-enrollment.
- •Continuous intravenous inotropic therapy.
- •Inability or unwillingness to comply with the study requirements.
- •Chronic kidney disease requiring hemodialysis or peritoneal dialysis.
- •Patients taking heparin, or heparin derivatives (e.g. low molecular weight heparins) for anticoagulation.
- •Other reason that would make the subject inappropriate for entry into this study.
研究组 & 干预措施
Stabilizer Only
Subjects treated with tafamidis selected to re-scan to determine the change over time in Evuzamitide uptake
干预措施: I 124-Evuzamitide (Drug)
Silencer Only
Subjects treated with vutrisiran selected to re-scan to determine the change over time in Evuzamitide uptake
干预措施: I 124-Evuzamitide (Drug)
Stabilizer and Silencer (tafamidis + patisiran)
Subjects treated with tafamidis and patisiran selected to re-scan to determine the change over time in Evuzamitide uptake
干预措施: I 124-Evuzamitide (Drug)
Stabilizer and Silencer (vutrisiran + diflunisal)
Subjects treated with vutrisiran and diflunisal selected to re-scan to determine the change over time in Evuzamitide uptake
干预措施: I 124-Evuzamitide (Drug)
结局指标
主要结局
Median of Uptake of Evuzamitide as Measured by Volume of Interest in Milliliters
时间窗: Up to one month after imaging
Volumes of interest (VOIs) were manually traced on PET emission images fused with CT images to define the left ventricular (LV) and right ventricular (RV) contours, including cavity blood pool. Blood pool activity concentration was measured in a 10-mm-diameter left atrial spherical VOI. For 124I-evuzamitide, we used a threshold of mean + 2 standard deviations of blood pool activity concentration.
Median of Change in Evuzamitide Uptake as Measured by Percentage Change in Injected Dose (%ID)
时间窗: Up to one month after imaging
Median percentage change in injected dose (%ID), calculated as VOI mean activity concentration x VOI volume/injected activity.
Median of Uptake of Evuzamitide as Measured by Cardiac Amyloid Activity (CAA) in Grams
时间窗: Up to one month after imaging
Cardiac amyloid activity (CAA) in grams is measured as VOI mean standardized uptake value times VOI volume. Standardized uptake value was defined as mean or maximal VOI activity concentration/(injected activity/bodyweight), while target-to-background ratio was considered VOI mean activity concentration/blood pool mean activity concentration. VOI volume was manually traced on PET emission images fused with CT images.
次要结局
未报告次要终点
研究者
Mathew S. Maurer, MD
Arnold and Arlene Goldstein Professor of Medicine
Columbia University