Terazosin and Parkinson's Disease Extension Study

NCT05109364 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00001770
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (3)

• Changes in 123I-MIBG reuptake - early Heart to Mediastinal ratio (H/M)

  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.

  Every 6 months for 3 years

• Changes in 123I-MIBG reuptake - late Heart to Mediastinal ratio (H/M)

  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.

  Every 6 months for 3 years

• Changes in 123I-MIBG - Washout ratio (WR)

  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%.

  Every 6 months for 3 years

Secondary Outcomes (4)

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

  3 years

• Changes in 123I-Ioflupane uptake

  Every year for three years

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

  3 years

• Heart Rate Variability Analysis (HRV) compared to MIBG results in predicting RBD conversion to PD/other synucleinopathies

  Every 6 months for 3 years

Other Outcomes (12)

• 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

  Every 6 months for 3 years

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

  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

  Every 6 months for 3 years

Study Arms (1)

terazosin therapy extension

EXPERIMENTAL

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.

Drug: Terazosin therapy

Interventions

Terazosin therapy DRUG

Primary procedures in this study are MIBG scan, DAT scan, NM-MRI, and terazosin 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 a1- Adrenergic Receptor Antagonist Terazosin, resulting in a decreased clinical conversion rate to parkinsonism.

terazosin therapy extension

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

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MeSH Terms

Conditions

Parkinson Disease, Secondary; REM Sleep Behavior Disorder; Parkinson Disease; Primary Dysautonomias; Nerve Degeneration

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Mental Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michele Tagliati, MD, FAAN

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Vice Chairman, Director of Movement Disorders

Study Record Dates

• First Submitted: October 13, 2021
• First Posted: November 5, 2021
• Study Start: September 23, 2022
• Primary Completion: March 10, 2026
• Study Completion: March 10, 2026
• Last Updated: March 2, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)