Clinical trial NCT05109364: Terazosin and Parkinson's Disease Extension Study
Official title: The Effect of Alpha1- Adrenergic Receptor Antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease: a Follow Up Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Symptomatic Parkinson Disease
REM Sleep Behavior Disorder
Pre-motor Parkinson's Disease
Keywords: Parkinson's disease
REM sleep behavior disorder (RBD)
Autonomic dysfunction
Neurodegeneration
Terazosin
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2021-11-05
Enrollment: 15
Sex: ALL
Minimum age (years): 50
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 selective post-synaptic a1-adrenergic blocker terazosin on serial in a population of subjects with defined pre-motor Parkinson's disease (PD) risks and abnormal imaging exams. Imaging changes will be correlated to the presence and severity of motor and non-motor symptoms of PD, measured by validated clinical scales and cardiac autonomic function tests.

Detailed description: The purpose of this study is to investigate the long-term effects of treatment with the selective post-synaptic a1-adrenergic blocker terazosin on serial 123 Ioflupane Dopamine Transporter single-photon emission-computed tomography (123I-FP DAT-SPECT) in a population of subjects with defined pre-motor PD risks (i.e., RBD and at least one among hyposmia, constipation, depression and color vision abnormality) and abnormal Iodine-123 meta-iodobenzylguanidine (123I-MIBG) uptake. Imaging changes will be correlated to the presence and severity of motor and non-motor symptoms of PD, measured by validated clinical scales and cardiac autonomic function tests. The rate of RBD clinical conversion to PD will be estimated and compared to available data in the literature.

Eligibility criteria: Inclusion Criteria:

* Enrolled in the study "The Effect of alpha1- adrenergic receptor antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease" (STUDY #000540)
* Capacity to give informed consent

Exclusion Criteria:

* Secondary Parkinsonism, including tardive
* Concurrent dementia defined by a score lower than 22 on The Montreal Cognitive Assessment (MoCA)
* Concurrent severe depression defined by a Beck Depression Inventory-Fast Screen (BDI fast screen) score greater than 13
* Comorbidities related to sympathetic nervous system (SNS) hyperactivity
* Heart failure (LVEF \<45%)
* Recent myocardial revascularization (\<12 weeks)
* Hypertension (systolic blood pressure SBP\>150mmHg (millimeters of mercury) or diastolic blood pressure DBP\>100mmHg)
* Chronic Atrial fibrillation
* Concurrent Use of Beta-adrenergic antagonist
* Diabetes mellitus
* Chronic Obstructive Pulmonary Disease (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 terazosin
* Recent myocardial infarction (\<48 h)
* Ongoing angina pectoris
* Cardiogenic shock or prolonged hypotension
* Breast-feeding
* Current use of phosphodiesterase type 5 inhibitors: sildenafil (ViagraTM), tadalafil (CialisTM), or vardenafil (LevitraTM)
* History of priapism (persistent and painful erection)
* Neurogenic orthostatic hypotension defined as symptomatic decrease in BP \> 20mmHg systolic or \> 10mmHg diastolic and HR increase \< 20bpm on supine to sitting or standing.
* Blood pressure less than 110 mm Hg systolic at screening or baseline visit
* Use of investigational drugs within 30 days before screening
* For female participant, pregnancy, or plans for child-bearing during study period
* Allergy/hypersensitivity to iodine or study medication

Primary outcomes:
measure: Changes in 123I-MIBG reuptake - early Heart to Mediastinal ratio (H/M)
timeFrame: Every 6 months for 3 years
measure: Changes in 123I-MIBG reuptake - late Heart to Mediastinal ratio (H/M)
timeFrame: Every 6 months for 3 years
measure: Changes in 123I-MIBG - Washout ratio (WR)
timeFrame: Every 6 months for 3 years
Secondary outcomes:
measure: Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population
timeFrame: 3 years
measure: Changes in 123I-Ioflupane uptake
timeFrame: Every year for three years
measure: Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies
timeFrame: 3 years
measure: Heart Rate Variability Analysis (HRV) compared to MIBG results in predicting RBD conversion to PD/other synucleinopathies
timeFrame: Every 6 months for 3 years
Other outcomes:
measure: MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III changes from without (OFF) medication between baseline and every 6 months for three years
timeFrame: Every 6 months for 3 years
measure: Non-Motor Symptoms Scale (NMSS) changes between baseline and every 6 months for three years
timeFrame: Every 6 months for 3 years
measure: Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) changes between baseline and every 6 months for three years
timeFrame: Every 6 months for 3 years
measure: Rapid Eyes Movement (REM) sleep Behavior Disorder Screening questionnaire (RBDSQ) changes between baseline and every 6 months for three years
timeFrame: Every 6 months for 3 years
measure: Smell changes as measured by University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: Every 6 months for 3 years
measure: Functional constipation score changes between baseline and every 6 months for three years
timeFrame: Every 6 months for 3 years
measure: Color vision changes, as assessed using Hardy, Rand and Rittler (HRR) pseudoisochromatic Plates, between baseline and every 6 months for three years
timeFrame: Every 6 months for 3 years
measure: Central insulin resistance changes between baseline and every 6 months for three years
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
measure: Peripheral insulin resistance (IR) 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: Cedars Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Michele Tagliati, MD, FAAN
role: PRINCIPAL_INVESTIGATOR
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