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

Cedars-Sinai Medical Center

Status and phase: Invitation-only; Phase 2

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

Treatments: Drug: Carvedilol

Study type: Interventional

Funder types: Other

Identifiers

NCT04218968

Study00000349

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

carvedilol therapy

Experimental group

Description:

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

Treatment:

Drug: Carvedilol