Terazosin and Parkinson's Disease Extension Study

February 26, 2026 updated by: Michele Tagliati, MD, Cedars-Sinai Medical Center

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: terazosin therapy extension
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in 123I-MIBG reuptake - early Heart to Mediastinal ratio (H/M)
Time Frame: 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.
Every 6 months for 3 years
Changes in 123I-MIBG reuptake - late Heart to Mediastinal ratio (H/M)
Time Frame: 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.
Every 6 months for 3 years
Changes in 123I-MIBG - Washout ratio (WR)
Time Frame: 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%.
Every 6 months for 3 years

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: 3 years
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
3 years
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
Time Frame: Every 6 months for 3 years
The Movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS) Part III will be administered at baseline and 26 weeks after study medication titration. Each item of the MDS-UPDRS has a possible rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe.Clinical scales will be performed without (OFF) medication in those subjects that might be receiving dopaminergic drugs
Every 6 months for 3 years
Non-Motor Symptoms Scale (NMSS) changes between baseline and every 6 months for three years
Time Frame: Every 6 months for 3 years
The NMSS measures non-motor symptoms over the previous month. Each symptom is scored with respect to: Severity: 0 = None, 1 = Mild; 2 = Moderate; 3 = Severe and Frequency: 1 = Rarely (<1/wk); 2 = Often (1/wk); 3 = Frequent (several times per week); 4 = Very Frequent (daily or all the time).
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
Time Frame: Every 6 months for 3 years
The SCOPA-AUT was developed to evaluate autonomic symptoms in patients with Parkinson's disease. The scale is self-completed by patients and consists of 25 items assessing the following domains: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women).
Every 6 months for 3 years
Rapid Eyes Movement (REM) sleep Behavior Disorder Screening questionnaire (RBDSQ) changes between baseline and every 6 months for three years
Time Frame: Every 6 months for 3 years
The RBDSQ is a 10-item, patient self-rating instrument assessing the subject's sleep behavior with short questions that have to be answered by either "yes" or "no" that address frequency and content of dreams, their relationship to nocturnal movements/behavior, injuries of the bed partner, nocturnal vocalization, etc. The maximum total score of the RBDSQ is 13 points.
Every 6 months for 3 years
Smell changes as measured by University of Pennsylvania Smell Identification Test (UPSIT)
Time Frame: Every 6 months for 3 years
University of Pennsylvania Smell Identification Test (UPSIT) changes.
Every 6 months for 3 years
Functional constipation score changes between baseline and every 6 months for three years
Time Frame: Every 6 months for 3 years
Functional constipation will be assessed at screening and at 26 weeks after study medication titration using a questionnaire based on modified The Rome III Criteria for Functional Digestive Disorders (ROME III diagnostic criteria), which focuses on symptoms including straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction or blockage, manual maneuvers to facilitate evacuation, and two or fewer bowel movements per week. This questionnaire is based on a six item self-report measures with a three point summated rating scale. The total score has a range of 0 to 12, with scores > 4 identifying functional constipation.
Every 6 months for 3 years
Color vision changes, as assessed using Hardy, Rand and Rittler (HRR) pseudoisochromatic Plates, between baseline and every 6 months for three years
Time Frame: Every 6 months for 3 years
Color vision changes will be assessed using HRR pseudoisochromatic Plates.
Every 6 months for 3 years
Central insulin resistance changes between baseline and every 6 months for three years
Time Frame: Every 6 months for 3 years
Measures of insulin sensitivity in neuronal-origin enriched plasma extracellular vesicles EVs (central IR) will be used to test the association of changes in such sensitivity to changes in MIBG uptake and clinical scores. For that purpose, plasma samples will be collected and stored and -80oC (celsius degrees) to allow for isolation of neuronal origin EVs at the completion of the study.
Every 6 months for 3 years
Differences in integrity of pigmented neurons in the locus coeruleus and substantia nigra between baseline, year one, year two and year three
Time Frame: 3 years
This outcome will be measured by the content of neuromelanin, a product of catecholamine metabolism in locus coeruleus (LC) and substantia nigra (SN).
3 years
Peripheral insulin resistance (IR) changes between baseline and every 6 months for three years.
Time Frame: Every 6 months for 3 years
Peripheral IR will be defined by the homeostasis model assessment of IR (HOMA-IR) defined as fasting glucose (mmol/L) x fasting insulin (mU/mL)/22.5. A cutoff HOMA index of 2.0, equivalent to <50% sensitivity, will be used to define IR. Subjects will be considered to have IR if they either have a HOMA≥2.0 and/or HbA1c≥5.7
Every 6 months for 3 years
Heart Rate Variability (HRV) changes between baseline and every 6 months for three years
Time Frame: 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.
Every 6 months for 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cedars-Sinai Medical Center

Investigators

  • Principal Investigator: Michele Tagliati, MD, FAAN, Cedars-Sinai Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2022

Primary Completion (Estimated)

March 10, 2026

Study Completion (Estimated)

March 10, 2026

Study Registration Dates

First Submitted

October 13, 2021

First Submitted That Met QC Criteria

October 26, 2021

First Posted (Actual)

November 5, 2021

Study Record Updates

Last Update Posted (Actual)

March 2, 2026

Last Update Submitted That Met QC Criteria

February 26, 2026

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00001770

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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