Terazosin and Parkinson's Disease Extension Study

Phase 2

Recruiting

• Conditions: Pre-motor Parkinson's Disease; Symptomatic Parkinson Disease; REM Sleep Behavior Disorder
• Interventions: Drug: Terazosin therapy

• Registration Number: NCT05109364
• Lead Sponsor: Cedars-Sinai Medical Center

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.

Study Timeline

• Study First Submitted: 2021-10-13
• Study First Submitted QC: 2021-10-26
• Study First Posted: 2021-11-05
• Study Start: 2022-09-23
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-26
• Primary Completion: 2025-11-01
• Study Completion: 2025-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
terazosin therapy extension	Terazosin therapy	Primary procedures in this study are MIBG scan, DAT scan, NM-MRI, and terazosin medication. 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 alpha1- adrenergic receptor antagonist terazosin, resulting in a decreased clinical conversion rate to parkinsonism.

Primary Outcome Measures

Name	Time	Method
Changes in 123I-MIBG reuptake - early Heart to Mediastinal ratio (H/M)	Every 6 months for 3 years	123I-MIBG early reuptake will be measured by Heart to Mediastinal ratio (H/M) which will be calculated from the early images after drawing regions of interest (7×7 pixels) over the upper mediastinum and circular ROI around the entire heart. MIBG abnormality cutoff will be set for values of late H/M \<2.2.
Changes in 123I-MIBG - Washout ratio (WR)	Every 6 months for 3 years	123I-MIBG Washout ratio (WR) will be calculated using the following formula: \[(early heart counts/pixel - early mediastinum counts/pixel) - (late heart counts/pixel decay-corrected - late mediastinum counts/pixel decay-corrected)\]/(early heart counts/pixel - early mediastinum counts/pixel). Care will be taken to exclude lung or liver from the myocardial and large vessels and lung from the mediastinum region of interest. MIBG abnormality cutoff will be set for values of WR \>30%.
Changes in 123I-MIBG reuptake - late Heart to Mediastinal ratio (H/M)	Every 6 months for 3 years	123I-MIBG late reuptake will be measured by Heart to Mediastinal ratio (H/M) which will be calculated from the late images after drawing regions of interest (7×7 pixels) over the upper mediastinum and circular ROI around the entire heart. MIBG abnormality cutoff will be set for values of late H/M \<2.2.

Secondary Outcome Measures

Name	Time	Method
Changes in 123I-Ioflupane uptake	Every year for three years	Measured by 123I-Ioflupane uptake, between baseline, year one, year two and year three.
Diagnosis of PD or other synucleinopathies by the end of 3 years in the study population	3 years	Diagnosis of PD will be defined or ruled out according to the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria
Sensitivity and specificity of DAT Scan compared to MIBG in predicting RBD conversion to PD/other synucleinopathies	3 years	Integrity of pigmented neurons of substantia nigra.
Heart Rate Variability Analysis (HRV) compared to MIBG results in predicting RBD conversion to PD/other synucleinopathies	Every 6 months for 3 years	Beat-to-beat intervals will be registered to assess sympatho-vagal balance. This measurement will be used for HRV analysis.

Trial Locations

Locations (1)

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States