dreams. A high percentage of individuals with idiopathic RBD (iRBD) are known to develop
conditions affecting the neurons in the brain such as Parkinson’s disease (PD). Based on the
increased risk to develop PD, individuals with iRBD are currently considered ideal candidates
for therapies that can possibly protects brain cells, due to the critical window of
opportunity to intervene early before brain cell loss progresses significantly.
Early changes of PD are associated with a number of symptoms including loss of smell,
constipation, anxiety and depression. In addition, early heart and brain abnormalities can be
visualized using specialized imaging techniques called 123I-MIBG myocardial scintigraphy
(MIBG) and dopamine transporter (DAT) single photon emission computerized tomography (SPECT)
respectively. The combined presence of certain symptoms and the use of these imaging
techniques are considered early markers of PD in individuals with iRBD.
In other conditions, like heart failure, MIBG abnormalities are reversed by drugs able to
block excessive adrenergic stimulation, known as beta-blockers. In this study the
investigators want to learn about the effect of treatment with the beta-blocker carvedilol on
MIBG abnormalities found in iRBD patients at risk to develop PD. The investigators believe
that reversing the MIBG abnormality might prelude to a slowing of the neurodegenerative
process. This drug is approved by the U.S. Food and Drug Administration (FDA) for congestive
heart failure, hypertension and left ventricular dysfunction after myocardial infarction.
However, carvedilol is not approved by the FDA in patients with iRBD at risk for PD. The
available doses for this drug oral formulations are 3.125mg, 6.25mg, 12.5mg and 25mg.
Changes visualized with the MIBG imaging technique will be correlated to the presence and
severity of neurological (i.e. tremors, stiffness, slow movements, walking difficulties) and
other symptoms associated with PD (i.e. abnormal smell, constipation, depression, color
vision abnormalities), as measured by specific clinical scales and exams.
Male or female of age between 30 and 75 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:
1. 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. 2. Functional constipation, assessed by a scores > 4 on a questionnaire based on modified
ROME III diagnostic criteria.
3. Color vision abnormality, as assessed using HRR Pseudoisochromatic Plates, in the
absence of congenital dyschromatopsia.
4. 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
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)
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
- Cedars Sinai Medical Center, Los Angeles, California, United States, 90048