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

Phase 2

• Conditions: REM Sleep Behavior Disorder; Pre-motor Parkinson Disease; Symptomatic Parkinson Disease
• Interventions: Drug: Carvedilol

• Registration Number: NCT04218968
• Lead Sponsor: Cedars-Sinai Medical Center

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.

Study Timeline

• Study First Submitted: 2019-12-26
• Study Start: 2019-12-30
• Study First Submitted QC: 2020-01-02
• Study First Posted: 2020-01-06
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-26
• Primary Completion: 2025-12-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
carvedilol therapy	Carvedilol	Twice daily oral doses of adrenergic blocker 12.5 mg or 25mg, according to patient tolerability.

Primary Outcome Measures

Name	Time	Method
Changes in 123I-Ioflupane uptake - DATscan	Every year for three years	Changes in 123I-Ioflupane uptake, as measured by specific binding ratio (SBR), between baseline, year one, year two and year three.

Secondary Outcome Measures

Name	Time	Method
Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population	Every year for 3 years	Clinical evaluation
Changes in 123I-MIBG late H/M	Every 6 months for 3 years	Changes in 123I-MIBG reuptake, as measured by late H/M ratio, between baseline and every six months for three years
Changes in 123I-MIBG WR rate	Every 6 months for 3 years	Changes in 123I-MIBG WR reuptake, as measured by WR rate, between baseline and every six months for three years
Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies	Every year for3 years	Changes in 123I-Ioflupane uptake, as measured by specific binding ratio (SBR), between baseline, year one, year two and year three.

Trial Locations

Locations (1)

Michele L Lima Gregorio; 🇺🇸 Los Angeles, California, United States