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The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson’s Disease: A Follow up Study


Brief Summary:

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
123. I-Metaiodobenzylguanidine (MIBG) scintigraphy.

Primary procedures in this study are MIBG scan, DAT scan, Neuromelanin Magnetic Resonance
Imaging (NM-MRI), and carvedilol titration. Subjects will return for research visits and
imaging 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.


Inclusion Criteria:

– Enrolled in the study “The Effect of Adrenergic Blocker Therapy on Cardiac and
Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson’s Disease”

– Capacity to give informed consent

Exclusion Criteria:

– 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


  • Cedars Sinai Medical Center, Los Angeles, California, United States, 90048
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