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NCT Number: NCT04218968

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

REM Sleep Behavior Disorder Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Mental Disorders Movement Disorders Nervous System Diseases Parasomnias Parkinson Disease, Secondary Parkinsonian Disorders Pre-motor Parkinson Disease REM Sleep Parasomnias Sleep Wake Disorders Symptomatic Parkinson Disease

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Michele L Lima Gregorio

Los Angeles, California, 90046, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Carvedilol

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.

Primary outcomes

  1. Changes in 123I-Ioflupane uptake - DATscan

    Time frame: 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 outcomes

  1. Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population

    Time frame: Every year for 3 years

    Clinical evaluation

  2. Changes in 123I-MIBG late H/M

    Time frame: 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

  3. Changes in 123I-MIBG WR rate

    Time frame: 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

  4. Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies

    Time frame: 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.

Other outcomes

  1. MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III

    Time frame: Every 6 months for 3 years

    MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III changes from OFF medication between baseline and every 6 months for three years

  2. Non-Motor Symptoms Scale (NMSS) changes

    Time frame: Every 6 months for 3 years

    Non-Motor Symptoms Scale (NMSS) changes between baseline and every 6 months for three years

  3. Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT)

    Time frame: Every 6 months for 3 years

    Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) changes between baseline and every 6 months for three years

  4. REM sleep Behavior Disorder Screening questionnaire (RBDSQ)

    Time frame: Every 6 months for 3 years

    REM sleep Behavior Disorder Screening questionnaire (RBDSQ) changes between baseline and every 6 months for three years

  5. University of Pennsylvania Smell Identification Test (UPSIT)

    Time frame: Every 6 months for 3 years

    University of Pennsylvania Smell Identification Test (UPSIT) changes between baseline and every 6 months for three years

  6. Functional constipation score changes

    Time frame: Every 6 months for 3 years

    Functional constipation score changes between baseline and every 6 months for three years. The total score has a range of 0 to 12, with scores > 4 identifying functional constipation

  7. Color vision changes

    Time frame: Every 6 months for 3 years

    Color vision changes, as assessed using HRR Pseudoisochromatic Plates, between baseline and every 6 months for three years

  8. Central and peripheral insulin resistance changes

    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

    Beat-to-beat intervals will be registered to assess sympatho-vagal balance every 6 months for 3 years

Sponsors and collaborators

Lead sponsor

Cedars-Sinai Medical Center

Other

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Jan 6, 2020
Registry last updated
Mar 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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