The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease: a Follow Up Study
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Changes in 123I-Ioflupane uptake - DATscan
研究概览
简要总结
The purpose of this study is to investigate the long-term effects of treatment with the adrenergic blocker carvedilol on serial DaTscan, a dopamine transporter (DAT) single photon emission computerized tomography (SPECT) imaging technique in a population of subjects with defined pre-motor Parkinson's disease risks (i.e., REM sleep Behavior Disorder (RBD) and at least one among hyposmia, constipation, depression and color vision abnormality) and abnormal 123I-Metaiodobenzylguanidine (MIBG) scintigraphy.
详细描述
Primary procedures in this study are MIBG scan, DAT scan, Neuromelanin Magnetic Resonance Imaging (NM-MRI), and carvedilol treatment. Subjects will return for research visits and imaging tests every six months for three years. We hypothesize that the rate of decline in DAT scan123I-Ioflupane uptake will be slower in subjects who have received the adrenergic blocker carvedilol, resulting in a decreased clinical phenoconversion rate to parkinsonism. If this is true, it might create a considerable window of opportunity for treatment with adrenergic blockers - or similar compounds able to reduce Sympathetic Nervous System (SNS) hyperactivity - which may result in long-term benefits such as delaying the neurodegenerative process and the onset of neurological symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enrolled in the study "The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease" (Pro#00053136)
- •Capacity to give informed consent
排除标准
- •Secondary Parkinsonism, including tardive
- •Concurrent dementia defined by a score lower than 22 on the MoCA
- •Concurrent severe depression defined by a BDI fast screen score greater than 13
- •Comorbidities related to SNS hyperactivity
- •Heart failure (LVEF <45%)
- •Recent myocardial revascularization (<12 weeks)
- •Hypertension (SBP>150mmHg or DBP>100mmHg)
- •Chronic Atrial fibrillation
- •Concurrent Use of Beta-adrenergic antagonist
- •Diabetes mellitus
- •Untreated Sever Sleep Apnea; Apnea-Hypopnea Index (AHI) > 30/h.
- •Severely reduced kidney function (Glomerular Filtration Rate<30ml/min)
- •Contraindications to the use of carvedilol
- •Asthma or bronchospasm
- •Recent myocardial infarction (<48 h)
- •Ongoing unstable angina
- •Cardiogenic shock or prolonged hypotension
- •Second or Third-Degree AV block
- •Significant valvular aortic stenosis
- •Obstructive cardiomyopathy, or constrictive pericarditis
- •Resting Heart Rate (RHR)< 45 Or Bradycardia (HR<60) with at least one of the following symptoms; Lightheadedness, dizziness, weakness, Altered mental status, Shortness of breath, Pre-Syncope, Syncope, Sick Sinus Syndrome, Stroke within the past 1 month, Severe Hepatic Dysfunction
- •Allergy/hypersensitivity to iodine or study medication
研究组 & 干预措施
carvedilol therapy
Twice daily oral doses of adrenergic blocker 12.5 mg or 25mg, according to patient tolerability.
干预措施: Carvedilol (Drug)
结局指标
主要结局
Changes in 123I-Ioflupane uptake - DATscan
时间窗: Every year for three years
Changes in 123I-Ioflupane uptake, as measured by specific binding ratio (SBR), between baseline, year one, year two and year three.
次要结局
- Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population(Every year for 3 years)
- Changes in 123I-MIBG late H/M(Every 6 months for 3 years)
- Changes in 123I-MIBG WR rate(Every 6 months for 3 years)
- Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies(Every year for3 years)
研究者
Michele Tagliati, MD
Professor and Vice Chairman, Director of Movement Disorders
Cedars-Sinai Medical Center