Adrenergic Blockers for Cardiac Changes in Early Parkinson's Disease (Protocol 53136)
REM Sleep Behavior Disorder, Pre-motor Parkinson Disease, Symptomatic Parkinson Disease
About this trial
This is an interventional treatment trial for REM Sleep Behavior Disorder focused on measuring Early Parkinson Disease, REM Sleep Behaviour Disorder (RBD), carvedilol, Autonomic dysfunction, Neurodegeneration
Eligibility Criteria
Inclusion Criteria:
Male or female of age between 25 and 85 years at time of enrollment.
Diagnosis of idiopathic REM sleep behavior disorder (iRBD) or Diagnosis of hyposmia. Diagnosis of RBD will be, established either as 'definite RBD' according to the criteria proposed by the International Classification of Sleep Disorders (ICSD)-2 [AASM, 2005] or 'probable RBD' following a score of 6 or higher in the RBD questionnaire (RBDSQ) with a score of at least 1 in subitems 6.1 to 6.4 of question 6.
At least one of the following:
- Diagnosis of hyposmia. Diagnosis of hyposmia will be established as a University of Pennsylvania Smell Identification Test (UPSIT) score < 20th percentile for the individual's age group and sex.
- Functional constipation, assessed by a scores > 4 on a questionnaire based on modified ROME III diagnostic criteria.
- Color vision abnormality, as assessed using HRR Pseudoisochromatic Plates, in the absence of congenital dyschromatopsia.
Symptoms of depression, as assessed by a Beck Depression Inventory (BDI) fast screen score >3 or concurrent use of antidepressant medications
- Abnormal 123I-MIBG myocardial scintigraphy, as defined by a Late H/M ratio < 2.2 and/or a WR >30%, with normal cardiac ejection fraction (LVEF >55%).
- 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)
Chronic Hypertension (SBP>140mmHg-DBP>90mmHg)
Atrial fibrillation
Diabetes mellitus
COPD
Sleep Apnea
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
Symptomatic Bradycardia (HR<60) or Sick Sinus Syndrome
Stroke within the past 1 month
Severe Hepatic Dysfunction
Allergy/hypersensitivity to iodine or study medication
Sites / Locations
- Cedars Sinai Medical CenterRecruiting
Arms of the Study
Arm 1
Experimental
carvedilol therapy
The dosage of carvedilol will be gradually increased from the initial recommended starting dose of 3.125 mg twice/daily, the target dose will be 25mg twice daily (50 mg/day) and participants will take 50 mg/day carvedilol for 6 months.Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose.