Cardiac Changes in Early Parkinson's Disease: a Follow Up Study

NCT ID: NCT04218968

Last Updated: 2024-11-26

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-30
• Study Completion Date: 2025-12-30

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

carvedilol therapy

Twice daily oral doses of adrenergic blocker 12.5 mg or 25mg, according to patient tolerability.

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

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.

Interventions

Carvedilol

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.

Intervention Type: DRUG

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Michele Tagliati, MD

Professor and Vice Chairman, Director of Movement Disorders

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michele L Lima Gregorio, MD, FAAN

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Michele L Lima Gregorio

Los Angeles, California, United States

Countries

United States

Other Identifiers

Study00000349

Identifier Type: -

Identifier Source: org_study_id