Comparison of [18F]RO-948, [18F]MK-6240, and [18F]AV-1451 TAU Radiopharmaceuticals in Patients With Alzheimer's Disease and Older Controls
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Tracer kinetics as measured by Standard Uptake Volume Ratio of radioligands
研究概览
简要总结
The primary objective of this study is to identify a new radioligand for imaging of tauopathy in Alzheimer's disease through direct comparisons of two potential candidates, [18F]RO-948 (formerly known as [18F]6958948) and [18F]MK-6240, and demonstration of the candidates' absence of off-target binding.
详细描述
This is an open label study to compare two new generation TAU radioligands, [18F]RO-948 (formerly known as [18F]6958948) and [18F]MK-6240, for imaging of tauopathy and demonstrate the radioligands' absence of off-target binding in patients with Alzheimer's disease (AD) and older healthy controls (OC). The study will directly compare AD and OC with these two next-generation TAU radio ligands and compare each of these radio ligands with the current most widely used first generation radioligand, [18F]AV-1451.
Up to 24 (12 AD and 12 OC, matched for age and sex with AD subjects) male and female subjects aged 50-100 will be enrolled in the study. The study consists of three cohorts.
- Cohort 1: 10 AD subjects and 10 aged and sex matched older controls will be enrolled. Subjects will be scanned twice, with each of the tracers [18F]RO-948 and [18F]MK-6240.
- Cohort 2A: No positron emission tomography (PET) scans will be done. Previous [18F]AV-1451 scans of selected aged matched OC subjects from the Baltimore Longitudinal Study of Aging (BLSA) study (IRB00047185) will be reanalyzed.
- Cohort 2B: 2 AD and 2 OC subjects who show high binding to the choroid plexus by a visual analog scale (high, low, and none) will be studied. Subjects will scanned twice with either: [18F]RO-948 or [18F]MK-6240 and a 2nd scan with [18F]AV-1451 in randomized order and within one month of each other.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •History or presence of a neurological diagnosis other than AD that may influence the outcome or analysis of the scan results examples include but are not limited to stroke, traumatic brain injury, space occupying lesions, non-Alzheimer's tauopathies, and Parkinson's disease.
- •Subjects with a medical history that includes known autosomal dominant AD mutations in amyloid precursor protein (APP) or presenilin (PS) 1, PS 2 or mutations in genes that cause other types of autosomal dominant familial dementia, e.g., microtubule-associated protein tau (MAPT)
- •History or presence of any clinically relevant hematological, hepatic, respiratory, cardiovascular, renal, metabolic, endocrine, or central nervous system (CNS) disease or other medical conditions that are not well controlled, may put the subject at risk, could interfere with the objectives of the study, or make the subject unsuitable for participation in the study for any other reason in the opinion of the principal investigator.
- •Clinically relevant pathological findings in physical examination, ECG, or laboratory values at the screening assessment that could interfere with the objectives of the study.
- •Known history of clinically significant infectious disease including AIDS or serological indication of acute or chronic hepatitis B or C or HIV infection.
- •Women of childbearing potential must not be pregnant, or nursing and serum human chorionic gonadotropin (HCG) must be negative at the time of Screening Visit, and urine HCG must be negative on all subsequent visits.
- •Loss or donation of more than 450 mL blood in the 4 months before screening or donation of plasma within 14 days of screening.
- •Current symptoms of allergy and or severe allergy to drugs in medical history.
- •History of drug or alcohol abuse or positive result from urine screen for drugs of abuse AD subjects on prescribed narcotics medications will not be excluded if urine drug screen is positive for the documented narcotic drugs.
- •Have received an investigational medication within the last 3 months or 5 elimination half-life, whichever is longer, prior to administration of the radiotracer.
- •Has had or is planning to have exposure to ionizing radiation that in combination with the study related tracer administrations and scanning procedures would result in a cumulative exposure that exceeds recommended exposure limits.
- •Contraindications of MRI
- •History of, or suffers from, claustrophobia or feels that he or she will be unable to lie still on their back in the MRI or PET scanner.
结局指标
主要结局
Tracer kinetics as measured by Standard Uptake Volume Ratio of radioligands
时间窗: 3 years
Standard Uptake Volume Ratio (SUVR) of the two newer radioligands, RO-948 and MK-6240, in the OC and AD patients.
Tracer kinetics as measured by distribution volume of radioligands
时间窗: 3 years
Distribution volume (Vt) of the two newer radioligands, RO-948 and MK-6240, in older cognitively-normal control subjects (OC) and in clinically diagnosed Alzheimer's Disease (AD) patients.
Tracer kinetics as measured by SUVR of radioligands in off-target binding regions
时间窗: 3 years
SUVR of the two newer radioligands, RO-948 and MK-6240, in older cognitively-normal control subjects (OC) and in clinically diagnosed Alzheimer's Disease (AD) patients in the off-target binding regions (basal ganglia, thalamus and choroid plexus).
Tracer kinetics as measured by distribution volume of radioligands in off-target binding regions
时间窗: 3 years
Distribution volume (Vt) of the two newer radioligands, RO-948 and MK-6240, in older cognitively-normal control subjects (OC) and in clinically diagnosed Alzheimer's Disease (AD) patients in the off-target binding regions (basal ganglia, thalamus and choroid plexus).
次要结局
- Tracer kinetics as measured by distribution volume of radioligands in participants with high binding of AV-1541(3 years)
- Tracer kinetics as measured by volume distribution of radioligands in the hippocampus(3 years)
- Tracer kinetics as measured by SUVR of radioligands in participants with high binding of AV-1541(3 years)
- Tracer kinetics as measured by SUVR of radioligands in the hippocampus(3 years)