We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cardiac Changes in Early Parkinson's Disease: A Follow up Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04218968
Recruitment Status : Enrolling by invitation
First Posted : January 6, 2020
Last Update Posted : August 26, 2022
Sponsor:
Information provided by (Responsible Party):
Michele Tagliati, MD, Cedars-Sinai Medical Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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 123. I-Metaiodobenzylguanidine (MIBG) scintigraphy.

Primary procedures in this study are MIBG scan, DAT scan, Neuromelanin Magnetic Resonance Imaging (NM-MRI), and carvedilol titration. Subjects will return for research visits and imaging 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.


Condition or disease Intervention/treatment Phase
REM Sleep Behavior Disorder Pre-motor Parkinson Disease Symptomatic Parkinson Disease Drug: Carvedilol Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease: A Follow up Study
Actual Study Start Date : December 30, 2019
Estimated Primary Completion Date : December 30, 2025
Estimated Study Completion Date : December 30, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Carvedilol

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: carvedilol therapy Drug: 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Changes in 123I-Ioflupane uptake, as measured by specific binding ratio (SBR), between baseline, year one, year two and year three. [ Time Frame: Every year for three years ]

Secondary Outcome Measures :
  1. Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population [ Time Frame: 3 years ]
  2. Changes in 123I-MIBG reuptake, as measured by late H/M ratio, between baseline and every six months for three years [ Time Frame: Every 6 months for 3 years ]
  3. Changes in 123I-MIBG reuptake, as measured by WR reduction, between baseline and every six months for three years [ Time Frame: Every 6 months for 3 years ]
  4. Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies [ Time Frame: 3 years ]

Other Outcome Measures:
  1. MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III changes from OFF medication between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
  2. Non-Motor Symptoms Scale (NMSS) changes between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
  3. Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) changes between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
  4. REM sleep Behavior Disorder Screening questionnaire (RBDSQ) changes between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
  5. University of Pennsylvania Smell Identification Test (UPSIT) changes between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
  6. Functional constipation score changes between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
  7. Color vision changes, as assessed using HRR Pseudoisochromatic Plates, between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
  8. Central and peripheral insulin resistance changes between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]
    Peripheral Insulin Resistance (IR) will be defined by testing for fasting plasma insulin (FPI), fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). HOMA index will be calculated by the formula: HOMA-IR = (FPI x FPG)/405 . A cutoff HOMA index of 2.0, equivalent to <50% sensitivity, will be used to define IR. Subjects were considered to have IR if they either had a HOMA≥2.0 and/or HbA1c≥5.7 . In addition, measures of insulin sensitivity in neuronal-origin enriched plasma EVs (central IR) will be used to test the association of changes in such sensitivity to changes in MIBG uptake and clinical scores from baseline and every 6 months. For that purpose, plasma samples will be collected and stored and -80oC to allow for isolation of neuronal origin EVs at the completion of the study

  9. Differences in integrity of pigmented neurons in the locus coeruleus and substantia nigra between baseline, year one, year two and year three [ Time Frame: 3 years ]
    This outcome will be measured by the content of neuromelanin, a product of cathecolamine metabolism in LC and SN.

  10. Correlation between changes in integrity of pigmented neurons of substantia nigra as measured by neuromelanin-sensitive magnetic resonance imaging (MRI) and 123I-Ioflupane uptake as measured by Dopamine Transporter Imaging (DAT scan) [ Time Frame: 3 years ]
    These measurements will be aggregated to calculate the correlation between changes in neuromelanin content as measured by NM-MRI and dopamine content as measured by DAT scan

  11. Heart Rate Variability (HRV) changes between baseline and every 6 months for three years [ Time Frame: Every 6 months for 3 years ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04218968


Locations
Layout table for location information
United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Michele Tagliati, MD, Professor and Vice Chairman, Director of Movement Disorders, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT04218968    
Other Study ID Numbers: Study00000349
First Posted: January 6, 2020    Key Record Dates
Last Update Posted: August 26, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Parkinson Disease
REM Sleep Behavior Disorder
Parkinson Disease, Secondary
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
REM Sleep Parasomnias
Parasomnias
Sleep Wake Disorders
 Carvedilol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Antioxidants
Protective Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists