An Exploratory Study of 18F-Labeled Hydroxyphenethylguanidines in Heart Failure Patients
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Composite measures based on radiotracer tissue uptake ratios (heart-to-lung ratio, heart-to-liver ratio, heart-to-blood ratio) and rates of metabolism in plasma (half-time, minutes) of [18F]4F-MHPG and [18F]3F-PHPG in patients with heart failure.
研究概览
简要总结
The main goal of this study is to test two new radioactive drugs, 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and 3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG) in human subjects with congestive heart failure.
Evaluations of these imaging agents will include their uptake in heart, lungs and liver, their metabolic breakdown in blood, and their kinetics in the heart. Based on these studies, the better of the two drugs will be chosen for further studies in patients with heart disease. After the better compound is chosen, additional measures of its imaging properties, metabolism and pharmacokinetics will be done in subjects with heart failure.
详细描述
The human heart contains many nerve fibers that are involved in controlling the heart's pumping function. Several heart diseases have been shown to damage the nerves in the heart. Studies have shown that damage to the heart nerves may be a cause of death in patients with diseases like heart failure or diabetes.
Two new radioactive drugs been developed at the University of Michigan for taking pictures of the nerve fibers in the heart using a medical imaging method called positron emission tomography (PET).
These two drugs are 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and 3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG). Initial PET imaging studies in normal human subjects (see NCT 02385877) have shown that [18F]4F-MHPG and [18F]3F-PHPG are each able to provide a detailed regional map of the distribution of nerve fibers in the heart.
In Stage 1 of this study, enrolled subjects with heart failure will undergo PET studies with [18F]4F-MHPG and [18F]3F-PHPG to allow direct comparison of the imaging properties, metabolism and pharmacokinetics of the two radioactive drugs in the same subjects.
A third PET scan with [13N]ammonia will be done to assess resting blood flow in different areas of the heart. The results of these studies will be used to select the better of the two tracers for further study in patients with heart disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80y
- •Cardiomyopathy (ischemic and non-ischemic)
- •Left ventricular ejection fraction (LVEF) < 35%
- •Clinically appropriate referral for surgical implantation of an implantable cardiodefibrillator (ICD) for primary prevention of sudden cardiac death
- •Not claustrophobic
- •Ability to lie flat for 90 min
- •Give informed consent
排除标准
- •Revascularization such as the placement of a stent or balloon angioplast in the preceding 40 days
- •Renal dysfunction with eGFR < 50 mL/min/1.73 m2
- •Currently taking medications or drugs that may alter PET scans of cardiac sympathetic nerve terminals with these tracers, including any of the following:
- •Tricyclic antidepressants, which inhibit the norepinephrine transporter, such as amitriptyline, desipramine, imipramine, etc.
- •Cold medications (e.g., Sudafed®, as they may contain sympathomimetic amines, such as phenylephrine, phenylpropanolamine, pseudoephedrine, etc.)
- •Nasal decongestants (some use phenylephrine as the active agent)
- •Cocaine (which inhibits the norepinephrine transporter)
- •Tetrabenazine (Xenazine, which inhibits VMAT2 transporters on vesicles inside neurons)
- •Monoamine oxidase inhibitors (MAOI)
- •Some antihypertensive drugs (reserpine, labetalol, α-methyldopa, and clonidine)
- •Pregnancy or lactation
- •Claustrophobia
- •Inability to lie flat for 90 min
研究组 & 干预措施
Stage 1
Subjects (n = 4 to 10) will be injected once with 20 mCi of [13N]ammonia and receive a 20 minute PET scan. They will then be injected once with 6.5 mCi of one of the two new drugs under study, [18F]4F-MHPG or [18F]3F-PHPG, and receive a 60 minute PET scan.
On a second visit to the clinic, subjects will be injected once with 6.5 mCi of [18F]3F-PHPG or [18F]4F-MHPG (whichever was not used for the first visit) and receive a 60 minute PET scan.
干预措施: [18F]4F-MHPG (Drug)
Stage 1
Subjects (n = 4 to 10) will be injected once with 20 mCi of [13N]ammonia and receive a 20 minute PET scan. They will then be injected once with 6.5 mCi of one of the two new drugs under study, [18F]4F-MHPG or [18F]3F-PHPG, and receive a 60 minute PET scan.
On a second visit to the clinic, subjects will be injected once with 6.5 mCi of [18F]3F-PHPG or [18F]4F-MHPG (whichever was not used for the first visit) and receive a 60 minute PET scan.
干预措施: [18F]3F-PHPG (Drug)
Stage 1
Subjects (n = 4 to 10) will be injected once with 20 mCi of [13N]ammonia and receive a 20 minute PET scan. They will then be injected once with 6.5 mCi of one of the two new drugs under study, [18F]4F-MHPG or [18F]3F-PHPG, and receive a 60 minute PET scan.
On a second visit to the clinic, subjects will be injected once with 6.5 mCi of [18F]3F-PHPG or [18F]4F-MHPG (whichever was not used for the first visit) and receive a 60 minute PET scan.
干预措施: [13N]ammonia (Drug)
Stage 2
Subjects (n = 20 to 26) will be injected with 20 mCi of [13N]ammonia and receive a 20 minute PET scan.
They will then be injected once with 6.5 mCi of [18F]4F-MHPG or [18F]3F-PHPG (whichever was chosen based on Stage 1 of the study) and receive a 60 minute PET scan. On a second visit to the clinic, subjects will be injected once with 20 mCi of [11C]HED and receive a 40 minute scan.
干预措施: [18F]4F-MHPG (Drug)
Stage 2
Subjects (n = 20 to 26) will be injected with 20 mCi of [13N]ammonia and receive a 20 minute PET scan.
They will then be injected once with 6.5 mCi of [18F]4F-MHPG or [18F]3F-PHPG (whichever was chosen based on Stage 1 of the study) and receive a 60 minute PET scan. On a second visit to the clinic, subjects will be injected once with 20 mCi of [11C]HED and receive a 40 minute scan.
干预措施: [18F]3F-PHPG (Drug)
Stage 2
Subjects (n = 20 to 26) will be injected with 20 mCi of [13N]ammonia and receive a 20 minute PET scan.
They will then be injected once with 6.5 mCi of [18F]4F-MHPG or [18F]3F-PHPG (whichever was chosen based on Stage 1 of the study) and receive a 60 minute PET scan. On a second visit to the clinic, subjects will be injected once with 20 mCi of [11C]HED and receive a 40 minute scan.
干预措施: [13N]ammonia (Drug)
Stage 2
Subjects (n = 20 to 26) will be injected with 20 mCi of [13N]ammonia and receive a 20 minute PET scan.
They will then be injected once with 6.5 mCi of [18F]4F-MHPG or [18F]3F-PHPG (whichever was chosen based on Stage 1 of the study) and receive a 60 minute PET scan. On a second visit to the clinic, subjects will be injected once with 20 mCi of [11C]HED and receive a 40 minute scan.
干预措施: [11C]HED (Drug)
结局指标
主要结局
Composite measures based on radiotracer tissue uptake ratios (heart-to-lung ratio, heart-to-liver ratio, heart-to-blood ratio) and rates of metabolism in plasma (half-time, minutes) of [18F]4F-MHPG and [18F]3F-PHPG in patients with heart failure.
时间窗: 12 months
These data on the relative imaging properties and metabolism of \[18F\]4F-MHPG and \[18F\]3F-PHPG in heart failure patients will be used to select the lead radiotracer for further clinical development.
次要结局
- Number of study participants with adverse events as a measure of safety and tolerability following intravenous administration of [18F]4F-MHPG or [18F]3F-PHPG.(Up to 30 days after [18F]4F-MHPG or [18F]3F-PHPG injection.)
- Quantitative measures of regional cardiac sympathetic nerve density in patients with heart failure using tracer kinetic analyses.(36 months)
研究者
David M. Raffel, Ph.D.
Research Associate Professor
University of Michigan