The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease: a Follow Up Study
Overview
- Phase
- Phase 2
- Intervention
- Carvedilol
- Conditions
- REM Sleep Behavior Disorder
- Sponsor
- Cedars-Sinai Medical Center
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Changes in 123I-Ioflupane uptake - DATscan
- Status
- Enrolling By Invitation
- Last Updated
- last year
Overview
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.
Investigators
Michele Tagliati, MD
Professor and Vice Chairman, Director of Movement Disorders
Cedars-Sinai Medical Center
Eligibility 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
Arms & Interventions
carvedilol therapy
Twice daily oral doses of adrenergic blocker 12.5 mg or 25mg, according to patient tolerability.
Intervention: Carvedilol
Outcomes
Primary Outcomes
Changes in 123I-Ioflupane uptake - DATscan
Time Frame: 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 Outcomes
- Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population(Every year for 3 years)
- Changes in 123I-MIBG late H/M(Every 6 months for 3 years)
- Changes in 123I-MIBG WR rate(Every 6 months for 3 years)
- Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies(Every year for3 years)