NCT04386317

Terazosin Effect on Cardiac Changes in Early Parkinson's Disease

The Effect of a1- Adrenergic Receptor Antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Cedars-Sinai Medical Center · Academic / Other
• Sex: All
• Age: 50 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Based on the increased risk to develop PD, individuals with iRBD are currently considered ideal candidates for therapies that can possibly protects brain cells, due to the critical window of opportunity to intervene early before brain cell loss progresses significantly. Early changes of PD are associated with a number of symptoms including loss of smell, constipation, anxiety and depression. In addition, early heart and brain abnormalities can be visualized using specialized imaging techniques called 123I-MIBG myocardial scintigraphy (MIBG) and dopamine transporter (DAT) single photon emission computerized tomography (SPECT) respectively. The combined presence of certain symptoms and the use of these imaging techniques are considered early markers of PD in individuals with iRBD. In this study the investigators want to learn about the effect of treatment with the adrenergic blocker terazosin on MIBG abnormalities in iRBD patients at risk to develop PD. The investigators believe that reversing the MIBG abnormality might prelude to a slowing of the neurodegenerative process. This drug is approved by the U.S. Food and Drug Administration (FDA) for Benign Prostatic Hyperplasia (BPH) and Hypertension. However, terazosin is not approved by the FDA in patients with iRBD at risk for PD. The available doses for this drug oral formulations are 1mg, 2 mg, 5mg and 10 mg. Changes visualized with the MIBG imaging technique will be correlated to the presence and severity of neurological (i.e. tremors, stiffness, slow movements, walking difficulties) and other symptoms associated with PD (i.e. abnormal smell, constipation, depression, color vision abnormalities), as measured by specific clinical scales and exams.

Conditions

• REM Sleep Behavior Disorder
• Pre-motor Parkinson's Disease
• Symptomatic Parkinson Disease

Interventions

Type	Name	Description
DRUG	Terazosin	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.

Timeline

• Start date: 2020-11-01
• Primary completion: 2025-12-10
• Completion: 2026-03-10
• First posted: 2020-05-13
• Last updated: 2026-03-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study