Pre-motor Parkinson Disease, REM Sleep Behavior Disorder, Symptomatic Parkinson Disease
Conditions
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 123I-Metaiodobenzylguanidine (MIBG) scintigraphy.
Detailed description
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.
Interventions
DRUGCarvedilol
Primary procedures in this study are MIBG scan, DAT scan, NM-MRI, and carvedilol titration. 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 adrenergic blocker carvedilol, resulting in a decreased clinical phenoconversion rate to parkinsonism.
Sponsors
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in 123I-Ioflupane uptake - DATscan | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in 123I-MIBG late H/M | Every 6 months for 3 years | Changes in 123I-MIBG reuptake, as measured by late H/M ratio, between baseline and every six months for three years |
| Changes in 123I-MIBG WR rate | Every 6 months for 3 years | Changes in 123I-MIBG WR reuptake, as measured by WR rate, between baseline and every six months for three years |
| Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population | Every year for 3 years | Clinical evaluation |
| Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies | Every year for3 years | Changes in 123I-Ioflupane uptake, as measured by specific binding ratio (SBR), between baseline, year one, year two and year three. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichele L Lima Gregorio, MD, FAAN
Cedars-Sinai Medical Center
Outcome results
None listed