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ACTIVE NOT RECRUITING

NCT03775096

PHASE2

Adrenergic Blockers for Cardiac Changes in Early Parkinson's Disease (Protocol 53136)

Sponsor: Michele Tagliati, MD

View on ClinicalTrials.gov

Summary

REM Behavior Sleep Disorder (RBD) is a sleep disorder causing people to 'act out' their 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.

Official title: The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease

Key Details

Gender

All

Age Range

50 Years - 85 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2019-04-04

Completion Date

2026-07-01

Last Updated

2026-03-02

Healthy Volunteers

Conditions

REM Sleep Behavior Disorder Pre-motor Parkinson Disease Symptomatic Parkinson Disease

Interventions

DRUG

Carvedilol

At the end of Baseline visit, carvedilol 3.125 twice daily will be initiated and maintained for 1 week, increased to 6.25twice daily (dispensed at week 1visit), to 12.5mg twice daily (dispensed at week 2) and a max dose of 25mg twice daily (dispensed at week 4 visit), as tolerated. A subject that cannot tolerate at least a 25 mg daily dose will be excluded from the study. Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose. The project will include a washout period at study end.

Inclusion Criteria: Male or female of age between 50 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: 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 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

Locations (1)

Michele L Lima Gregorio

Los Angeles, California, United States