Cardiac Changes in Early Parkinson's Disease: A Follow up Study

• Status: Enrolling by invitation
• Trial end date: 2022-12-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cedars-Sinai Medical Center
• Treatments: Adrenergic Antagonists; Carvedilol

Criteria

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" (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