The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson’s Disease: A Follow up Study
Sponsor:
Brief Summary:
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.
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”
(Pro#00053136)
– 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
– COPD
– 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
Locations
- Cedars Sinai Medical Center, Los Angeles, California, United States, 90048
