Clinical trial NCT04218968: Cardiac Changes in Early Parkinson's Disease: a Follow Up Study
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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: REM Sleep Behavior Disorder
Pre-motor Parkinson Disease
Symptomatic Parkinson Disease
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Changes in 123I-Ioflupane uptake - DATscan
timeFrame: Every year for three years
Secondary outcomes:
measure: Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population
timeFrame: Every year for 3 years
measure: Changes in 123I-MIBG late H/M
timeFrame: Every 6 months for 3 years
measure: Changes in 123I-MIBG WR rate
timeFrame: Every 6 months for 3 years
measure: Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies
timeFrame: Every year for3 years
Other outcomes:
measure: MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
timeFrame: Every 6 months for 3 years
measure: Non-Motor Symptoms Scale (NMSS) changes
timeFrame: Every 6 months for 3 years
measure: Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT)
timeFrame: Every 6 months for 3 years
measure: REM sleep Behavior Disorder Screening questionnaire (RBDSQ)
timeFrame: Every 6 months for 3 years
measure: University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: Every 6 months for 3 years
measure: Functional constipation score changes
timeFrame: Every 6 months for 3 years
measure: Color vision changes
timeFrame: Every 6 months for 3 years
measure: Central and peripheral insulin resistance changes
timeFrame: Every 6 months for 3 years
measure: Differences in integrity of pigmented neurons in the locus coeruleus and substantia nigra between baseline, year one, year two and year three
timeFrame: 3 years
measure: 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)
timeFrame: 3 years
measure: Heart Rate Variability (HRV) changes between baseline and every 6 months for three years
timeFrame: Every 6 months for 3 years
Locations:
city: Los Angeles
country: United States
facility: Michele L Lima Gregorio
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Michele L Lima Gregorio, MD, FAAN
role: PRINCIPAL_INVESTIGATOR
References: