Terazosin Effect on Cardiac Changes in Early Parkinson's Disease

NCT04386317 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Study#000540
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's disease (PD) is characterized by many non-motor symptoms that occur several years before the diagnosis, in particular idiopathic REM behavior disorder (iRBD), which is associated with autonomic impairment. The purpose of this study is to investigate the effect of treatment with the selective post-synaptic a1-adrenergic blocker terazosin on 123I-MIBG myocardial uptake in a population of subjects with defined pre-motor PD risks (i.e. hyposmia and RBD) and abnormal baseline 123I-MIBG uptake, with or without 123I-Ioflupane uptake abnormality or PD motor symptoms. Scintigraphic changes will be correlated to motor and non-motor severity 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

Outcome Measures

Primary Outcomes (1)

• Differences in 123I-MIBG reuptake, as measured by early and late Heart to mediastinum (H/M) ratio, and Washout Ration (WR), at 26 weeks of treatment with the adrenergic blocker terazosin

  1\) Differences in 123I-MIBG reuptake, as measured by early and late H/M ratio, and WR, at 26 weeks of treatment with the adrenergic blocker Terazosin.

  At baseline and at 26 weeks after medication titration

Secondary Outcomes (3)

• Incidence of adverse events

  At baseline and at 26 weeks after medication titration

• Heart Rate variability changes from baseline at 26 weeks after study medication titration

  At baseline and at 26 weeks after medication titration

• Incidence of abnormal vital signs

  At baseline and at 26 weeks after medication titration

Study Arms (1)

terazosin therapy

EXPERIMENTAL

Daily oral doses of adrenergic blocker 5 mg or 10 mg. The dosage will be gradually increased from the initial recommended starting dose of 1 mg daily at bedtime and titrated stepwise to 2mg, 5mg or 10 mg weekly, according to patient tolerability, as measured by subjective complaints, arterial blood pressure and heart rate. The target dose will be 5 mg or 10 mg daily based on subject's tolerability.

Drug: Terazosin

Interventions

Terazosin DRUG

Fifteen patients with defined pre-motor PD risk and abnormal baseline 123I-MIBG uptake, with or without 123I-Ioflupane uptake abnormality or PD motor symptoms, will be recruited to receive daily oral doses of terazosin 5 mg or 10 mg. The dosage of terazosin will be gradually increased from the initial recommended starting dose of 1 mg daily at bedtime and titrated stepwise to 2mg, 5mg or 10 mg weekly, according to patient tolerability, as measured by subjective complaints, arterial blood pressure and heart rate. The target dose will be 5 mg or 10 mg daily based on subject's tolerability. Development of incompatibility will be addressed by individually adjusting the dose of terazosin.

terazosin therapy

Eligibility Criteria

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

You may qualify if:

• Male or female of age between 50 and 85 years at time of enrollment.
• Diagnosis of idiopathic REM sleep behavior disorder (iRBD), established either as 'definite RBD' according to the criteria proposed by the International Classification of Sleep Disorders (ICSD)-2 \[AASM, 2005\] or 'probable RBD' following a score of 6 or higher in the RBD questionnaire (RBDSQ) \[Nomura et al, 2011\], with a score of at least 1 in subitems 6.1 to 6.4 of question 6 \[Halsband et al, 2018\].
• At least one of the following:
• Diagnosis of hyposmia, established as a University of Pennsylvania Smell Identification Test (UPSIT) score \< 20th percentile for the individual's age group and sex.
• Functional constipation assessed by a scores \> 4 on a questionnaire based on modified ROME IV diagnostic criteria.
• Color vision abnormality, as assessed using HRR Pseudoisochromatic Plates, in the absence of congenital dyschromatopsia
• Symptoms of depression, as assessed by a Beck Depression Inventory (BDI) fast screen score \>3 or concurrent use of antidepressant medications.
• Abnormal 123I-MIBG myocardial scintigraphy, as defined by a Late H/M ratio \< 2.2 and/or a WR \>20%, with normal cardiac ejection fraction (LVEF \>55%).
• 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 MOCA
• Concurrent severe depression defined by a BDI fast screen score greater than 13
• Comorbidites related to SNS hyperactivity
• Heart failure (LVEF\< 45%)
• Recent myocardial revascularization (\< 12 weeks)
• Hypertension (SBP \>150 mmHg or DBP\> 100mmHg)
• Chronic Atrial fibrillation
• Concurrent use of Alpha- adrenergic antagonist
• Diabetes mellitus
• COPD
• Untreated Severe Sleep Apnea; Apnea-Hypopnea Index (AHI) \> 30/h.
• Contraindication to the use of Terazosin
• Recent myocardial infarction (\< 48 h)
• Ongoing angina pectoris

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Michele L Lima Gregorio

Los Angeles, California, 90046, United States

Location

MeSH Terms

Conditions

REM Sleep Behavior Disorder; Parkinson Disease, Secondary

Interventions

Terazosin

Condition Hierarchy (Ancestors)

REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders

Study Officials

• Michele L Tagliati, MD

  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: April 24, 2020
• First Posted: May 13, 2020
• Study Start: November 1, 2020
• Primary Completion: December 10, 2025
• Study Completion: March 10, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)