The TZ-PD trial will be a 1:1 (active:placebo) randomized, double-blind, placebo-controlled Phase II trial to evaluate the safety and tolerability of terazosin for the treatment of PD.

This will be a single center, randomized, double-blind, controlled, pilot study to assess the safety and tolerability of terazosin (TZ) at a dose of 5 milligrams (MG) daily for patients with PD. The primary goal of this study is to assess the safety and tolerability of TZ in patients with PD. This is a pilot study and is not powered to assess efficacy of this medication. Our hope is that this study will guide future studies of this (and similar) medications for the disease modification of PD. This study is also aimed to learn more about how patients with produce and use energy and if TZ can help to reverse energy deficits that appear in PD.

Inclusion Criteria:

• Men or women aged 40 and older with the diagnosis of idiopathic PD per UK Brain Bank criteria
• Hoehn-Yahr Stage I-III, on stable dopaminergic treatment regimen for ≥4 weeks prior to baseline.

Exclusion Criteria:

• Subjects unwilling or unable to give informed consent
• Secondary parkinsonism (e.g., drug induced)
• Parkinson-plus syndromes
• History of brain surgery for PD such as deep brain stimulation
• No confounding acute or unstable medical, psychiatric, orthopedic condition. Subjects who have hypertension, diabetes mellitus, depression, or other common age-related illness will be included if their disease under control with stable treatment regimen for at least 30 days.
• Neurogenic orthostatic hypotension defined as symptomatic decrease in BP > 20mmHg systolic or > 10mmHg diastolic and HR increase < 20bpm on supine to sitting or standing.
• Clinically significant traumatic brain injury or post-traumatic stress disorder
• Presence of other known medical or psychiatric comorbidity that in the investigator's opinion would compromise participation in the study
• Presence of dementia per Movement Disorder Society Level I criteria
• Major depression, bipolar affective disorder, or other mental health disorders that are sufficiently severe to increase adverse event risk or impact neuropathy assessment in the opinion of the responsible site principal investigator.
• Subjects with clinically significant depression as determined by a Beck Depression Inventory score greater than 21 at the screening visit
• Current suicidal ideation within one year prior to the baseline visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS)
• If the participant has a Beck Anxiety Score greater than 22 at the initial screening visit.
• History of exposure to typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to the baseline visit
• Use of investigational drugs within 30 days before screening
• Subjects have to be on a stable regimen of central nervous system acting medications (benzodiazepines, antidepressants, hypnotics) for 30 days prior to the baseline visit
• Use of doxazosin, alfuzosin, prazosin, or tamsulosin
• For female participant, pregnancy, or plans for child-bearing during study period
• Participant is restricted from traveling to and from the study site

Upon reasonable request with justification for request from qualified researchers, anonymized data will be shared.

One year after completion of this study

Qualified researchers may contact the PI of this study with reasonable requests for data to be shared. Inquiries must include what hypothesis the researcher intends to test using the shared data.

12 week

-Recruitment halted early due to the onset of the COVID-19 Pandemic.