The Effect of alpha1- Adrenergic Receptor Antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease: A Follow up Study
概览
- 阶段
- 2 期
- 干预措施
- Terazosin therapy
- 疾病 / 适应症
- Symptomatic Parkinson Disease
- 发起方
- Cedars-Sinai Medical Center
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Changes in 123I-MIBG reuptake - early Heart to Mediastinal ratio (H/M)
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
The purpose of this study is to investigate the long-term effects of treatment with the selective post-synaptic a1-adrenergic blocker terazosin on serial in a population of subjects with defined pre-motor Parkinson's disease (PD) risks and abnormal imaging exams. Imaging changes will be correlated to the presence and severity of motor and non-motor symptoms of PD, measured by validated clinical scales and cardiac autonomic function tests.
详细描述
The purpose of this study is to investigate the long-term effects of treatment with the selective post-synaptic a1-adrenergic blocker terazosin on serial 123 Ioflupane Dopamine Transporter single-photon emission-computed tomography (123I-FP DAT-SPECT) in a population of subjects with defined pre-motor PD risks (i.e., RBD and at least one among hyposmia, constipation, depression and color vision abnormality) and abnormal Iodine-123 meta-iodobenzylguanidine (123I-MIBG) uptake. Imaging changes will be correlated to the presence and severity of motor and non-motor symptoms of PD, measured by validated clinical scales and cardiac autonomic function tests. The rate of RBD clinical conversion to PD will be estimated and compared to available data in the literature.
研究者
Michele Tagliati, MD
Professor and Vice Chairman, Director of Movement Disorders
Cedars-Sinai Medical Center
入排标准
入选标准
- •Enrolled in the study "The Effect of alpha1- adrenergic receptor antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease" (STUDY #000540)
- •Capacity to give informed consent
排除标准
- •Secondary Parkinsonism, including tardive
- •Concurrent dementia defined by a score lower than 22 on The Montreal Cognitive Assessment (MoCA)
- •Concurrent severe depression defined by a Beck Depression Inventory-Fast Screen (BDI fast screen) score greater than 13
- •Comorbidities related to sympathetic nervous system (SNS) hyperactivity
- •Heart failure (LVEF \<45%)
- •Recent myocardial revascularization (\<12 weeks)
- •Hypertension (systolic blood pressure SBP\>150mmHg (millimeters of mercury) or diastolic blood pressure DBP\>100mmHg)
- •Chronic Atrial fibrillation
- •Concurrent Use of Beta-adrenergic antagonist
- •Diabetes mellitus
研究组 & 干预措施
terazosin therapy extension
Primary procedures in this study are MIBG scan, DAT scan, NM-MRI, and terazosin medication. Subjects will return for research visits and imaging every six months for three years. The investigators hypothesize that the rate of decline in DAT scan123I-Ioflupane uptake will be slower in subjects who have received the alpha1- adrenergic receptor antagonist terazosin, resulting in a decreased clinical conversion rate to parkinsonism.
干预措施: Terazosin therapy
结局指标
主要结局
Changes in 123I-MIBG reuptake - early Heart to Mediastinal ratio (H/M)
时间窗: Every 6 months for 3 years
123I-MIBG early reuptake will be measured by Heart to Mediastinal ratio (H/M) which will be calculated from the early images after drawing regions of interest (7×7 pixels) over the upper mediastinum and circular ROI around the entire heart. MIBG abnormality cutoff will be set for values of late H/M \<2.2.
Changes in 123I-MIBG - Washout ratio (WR)
时间窗: Every 6 months for 3 years
123I-MIBG Washout ratio (WR) will be calculated using the following formula: \[(early heart counts/pixel - early mediastinum counts/pixel) - (late heart counts/pixel decay-corrected - late mediastinum counts/pixel decay-corrected)\]/(early heart counts/pixel - early mediastinum counts/pixel). Care will be taken to exclude lung or liver from the myocardial and large vessels and lung from the mediastinum region of interest. MIBG abnormality cutoff will be set for values of WR \>30%.
Changes in 123I-MIBG reuptake - late Heart to Mediastinal ratio (H/M)
时间窗: Every 6 months for 3 years
123I-MIBG late reuptake will be measured by Heart to Mediastinal ratio (H/M) which will be calculated from the late images after drawing regions of interest (7×7 pixels) over the upper mediastinum and circular ROI around the entire heart. MIBG abnormality cutoff will be set for values of late H/M \<2.2.
次要结局
- Changes in 123I-Ioflupane uptake(Every year for three years)
- Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population(3 years)
- Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies(3 years)
- Heart Rate Variability Analysis (HRV) compared to MIBG results in predicting RBD conversion to PD/other synucleinopathies(Every 6 months for 3 years)