Ignite Creation Date:
2025-12-24 @ 5:40 PM
Ignite Modification Date:
2025-12-25 @ 3:09 PM
Study NCT ID:
NCT04218968
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-11-26
First Post:
2019-12-26
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Cardiac Changes in Early Parkinson's Disease: a Follow Up Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020187', 'term': 'REM Sleep Behavior Disorder'}, {'id': 'D010302', 'term': 'Parkinson Disease, Secondary'}], 'ancestors': [{'id': 'D020923', 'term': 'REM Sleep Parasomnias'}, {'id': 'D020447', 'term': 'Parasomnias'}, {'id': 'D012893', 'term': 'Sleep Wake Disorders'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D020734', 'term': 'Parkinsonian Disorders'}, {'id': 'D001480', 'term': 'Basal Ganglia Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009069', 'term': 'Movement Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077261', 'term': 'Carvedilol'}], 'ancestors': [{'id': 'D011412', 'term': 'Propanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D020005', 'term': 'Propanols'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D002227', 'term': 'Carbazoles'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006575', 'term': 'Heterocyclic Compounds, 3-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 15}}, 'statusModule': {'overallStatus': 'ENROLLING_BY_INVITATION', 'startDateStruct': {'date': '2019-12-30', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-10', 'completionDateStruct': {'date': '2025-12-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-11-22', 'studyFirstSubmitDate': '2019-12-26', 'studyFirstSubmitQcDate': '2020-01-02', 'lastUpdatePostDateStruct': {'date': '2024-11-26', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-01-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': "MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III", 'timeFrame': 'Every 6 months for 3 years', 'description': "MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III changes from OFF medication between baseline and every 6 months for three years"}, {'measure': 'Non-Motor Symptoms Scale (NMSS) changes', 'timeFrame': 'Every 6 months for 3 years', 'description': 'Non-Motor Symptoms Scale (NMSS) changes between baseline and every 6 months for three years'}, {'measure': "Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT)", 'timeFrame': 'Every 6 months for 3 years', 'description': "Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) changes between baseline and every 6 months for three years"}, {'measure': 'REM sleep Behavior Disorder Screening questionnaire (RBDSQ)', 'timeFrame': 'Every 6 months for 3 years', 'description': 'REM sleep Behavior Disorder Screening questionnaire (RBDSQ) changes between baseline and every 6 months for three years'}, {'measure': 'University of Pennsylvania Smell Identification Test (UPSIT)', 'timeFrame': 'Every 6 months for 3 years', 'description': 'University of Pennsylvania Smell Identification Test (UPSIT) changes between baseline and every 6 months for three years'}, {'measure': 'Functional constipation score changes', 'timeFrame': 'Every 6 months for 3 years', 'description': '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'}, {'measure': 'Color vision changes', 'timeFrame': 'Every 6 months for 3 years', 'description': 'Color vision changes, as assessed using HRR Pseudoisochromatic Plates, between baseline and every 6 months for three years'}, {'measure': 'Central and peripheral insulin resistance changes', 'timeFrame': 'Every 6 months for 3 years', 'description': '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'}, {'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', 'description': 'This outcome will be measured by the content of neuromelanin, a product of cathecolamine metabolism in LC and SN.'}, {'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', 'description': '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'}, {'measure': 'Heart Rate Variability (HRV) changes between baseline and every 6 months for three years', 'timeFrame': 'Every 6 months for 3 years', 'description': 'Beat-to-beat intervals will be registered to assess sympatho-vagal balance every 6 months for 3 years'}], 'primaryOutcomes': [{'measure': 'Changes in 123I-Ioflupane uptake - DATscan', 'timeFrame': 'Every year for three years', 'description': 'Changes in 123I-Ioflupane uptake, as measured by specific binding ratio (SBR), between baseline, year one, year two and year three.'}], 'secondaryOutcomes': [{'measure': 'Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population', 'timeFrame': 'Every year for 3 years', 'description': 'Clinical evaluation'}, {'measure': 'Changes in 123I-MIBG late H/M', 'timeFrame': 'Every 6 months for 3 years', 'description': 'Changes in 123I-MIBG reuptake, as measured by late H/M ratio, between baseline and every six months for three years'}, {'measure': 'Changes in 123I-MIBG WR rate', 'timeFrame': 'Every 6 months for 3 years', 'description': 'Changes in 123I-MIBG WR reuptake, as measured by WR rate, between baseline and every six months for three years'}, {'measure': 'Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies', 'timeFrame': 'Every year for3 years', 'description': 'Changes in 123I-Ioflupane uptake, as measured by specific binding ratio (SBR), between baseline, year one, year two and year three.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['REM Sleep Behavior Disorder', 'Pre-motor Parkinson Disease', 'Symptomatic Parkinson Disease']}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 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)\n* Capacity to give informed consent\n\nExclusion Criteria:\n\n* Secondary Parkinsonism, including tardive\n* Concurrent dementia defined by a score lower than 22 on the MoCA\n* Concurrent severe depression defined by a BDI fast screen score greater than 13\n* Comorbidities related to SNS hyperactivity\n\n * Heart failure (LVEF \\<45%)\n * Recent myocardial revascularization (\\<12 weeks)\n * Hypertension (SBP\\>150mmHg or DBP\\>100mmHg)\n * Chronic Atrial fibrillation\n * Concurrent Use of Beta-adrenergic antagonist\n * Diabetes mellitus\n * COPD\n * Untreated Sever Sleep Apnea; Apnea-Hypopnea Index (AHI) \\> 30/h.\n * Severely reduced kidney function (Glomerular Filtration Rate\\<30ml/min)\n* Contraindications to the use of carvedilol\n\n * Asthma or bronchospasm\n * Recent myocardial infarction (\\<48 h)\n * Ongoing unstable angina\n * Cardiogenic shock or prolonged hypotension\n * Second or Third-Degree AV block\n * Significant valvular aortic stenosis\n * Obstructive cardiomyopathy, or constrictive pericarditis\n * 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\n* Allergy/hypersensitivity to iodine or study medication'}, 'identificationModule': {'nctId': 'NCT04218968', 'briefTitle': "Cardiac Changes in Early Parkinson's Disease: a Follow Up Study", 'organization': {'class': 'OTHER', 'fullName': 'Cedars-Sinai Medical Center'}, 'officialTitle': "The Effect of Adrenergic Blocker Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease: a Follow Up Study", 'orgStudyIdInfo': {'id': 'Study00000349'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'carvedilol therapy', 'description': 'Twice daily oral doses of adrenergic blocker 12.5 mg or 25mg, according to patient tolerability.', 'interventionNames': ['Drug: Carvedilol']}], 'interventions': [{'name': 'Carvedilol', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['carvedilol therapy']}]}, 'contactsLocationsModule': {'locations': [{'zip': '90046', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'Michele L Lima Gregorio', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}], 'overallOfficials': [{'name': 'Michele L Lima Gregorio, MD, FAAN', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Cedars-Sinai Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Cedars-Sinai Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor and Vice Chairman, Director of Movement Disorders', 'investigatorFullName': 'Michele Tagliati, MD', 'investigatorAffiliation': 'Cedars-Sinai Medical Center'}}}}