Terazosin And Metabolic Engagement in Parkinson's Disease

NCT ID: NCT07288450

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-09-01
• Study Completion Date: 2031-09-01

Brief Summary

To assess target engagement of terazosin (TZ) at multiple doses (1 mg/day, 3 mg/day, and 5 mg/day) and to assess sustained target engagement over 6 months relative to placebo in patients with Parkinson's Disease (PD). Target engagement will be measured using a whole blood luminescence assay to quantify Adenosine Triphosphate (ATP) and a plasma metabolomics assay. A subset of randomized participants will also undergo imaging studies to quantify cerebral ATP using 31P-magnetic resonance spectroscopy (31P-MRS) and 18F-fluurodeoxyglucosed positron emission tomography (18F-FDG PET) to assess changes in glucose uptake in response to TZ. The investigators will compare the mean change from baseline in these assays between the TZ and placebo groups. The null hypothesis to be tested is that TZ does not engage its target (phosphoglycerate kinase 1, or PGK1) and does not lead to increases in the outcome variables of interest. A total of 100 patients with early PD will be recruited. Participants will be randomized to TZ or placebo in a 60:40 fashion to account for predicted dropouts in the TZ group. Study treatment will be administered for 26 weeks, followed by a four-week washout period.

Detailed Description

Terazosin (TZ) has the potential to be repurposed for use as the first disease-modifying treatment of Parkinson's disease (PD). This would have substantial implications for patients with PD and for society. TZ may provide a safe and low-cost treatment option for individuals with PD. If TZ proves beneficial for the treatment of PD, the proposed study design will efficiently facilitate the availability of a much-needed medication by reducing the time and costs typically associated with drug discovery. For these reasons, the study should be given high priority given the extremely favorable cost-to-benefit ratio.

Consistent with prior studies, subjects who have received a diagnosis of PD within the preceding three years and who are taking no more than two dopaminergic medications at the time of screening will be enrolled. This criterion ensures that the pharmacodynamics of TZ are assessed in a population most representative of the largest number of patients with PD.

Following randomization, patients will remain on therapy for 26 weeks. The extended duration of the study is intended to assess sustained target engagement of TZ in patients with PD.

Risk/Benefit Assessment TZ is associated with an increased risk of orthostatic hypotension. This risk is particularly relevant in PD, where the prevalence of orthostatic hypotension is significantly higher compared to healthy controls. Patients with PD are also more susceptible to falls, which could be exacerbated by orthostatic hypotension. Data from the Truven database demonstrated that patients with PD who were using TZ did not have a significantly increased prevalence of ICD-9 codes related to falls compared to PD patients not using TZ. These findings suggest that the risk of orthostatic hypotension is not elevated significantly at a population level, though it remains a concern for individual participants. Importantly, no serious adverse events were reported in a pilot study. Mild side effects such as dizziness and lightheadedness were more common in participants taking TZ, and dropout rates were higher in this group due to these side effects. Therefore, accounting for the potential for higher dropout rates is imperative. This provides the rationale for enrolling more subjects into the TZ group to ensure adequate statistical power even if dropout rates are elevated.

TZ is also associated with additional adverse effects, including peripheral edema, palpitations, nausea, asthenia, dizziness, headache, and somnolence. Despite these risks, the potential benefit of TZ is significant given the absence of currently available treatments that slow the progression of PD. The proposed study will provide critical insights into both short-term and sustained target engagement of TZ in patients with PD.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Active arm

Terazosin hydrochloride

Group Type: EXPERIMENTAL

Terazosin Hydrochloride

Intervention Type: DRUG

TZ is an a1-adrenergic receptor antagonist that is FDA-approved to treat benign prostatic hyperplasia (BPH) and hypertension.

Placebo

Placebo control

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo control for Terazosin

Interventions

Terazosin Hydrochloride

TZ is an a1-adrenergic receptor antagonist that is FDA-approved to treat benign prostatic hyperplasia (BPH) and hypertension.

Intervention Type: DRUG

Placebo

Placebo control for Terazosin

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 50-80 years old at the time of enrollment with a diagnosis of idiopathic PD per the Movement Disorder Society's Diagnostic Criteria.
• Subjects must NOT be taking more than 2 dopaminergic treatments for their PD at the time of enrollment.
• Practically defined OFF Hoehn and Yahr score of 0-2.
• Diagnosis of PD made within the preceding 3 years.

Exclusion Criteria

• • Orthostatic hypotension at screening is defined as decrease in BP > 20 mmHg systolic or > 10 mmHg diastolic and HR increase <20 bpm on transition from supine to sitting or standing.

• Known allergy or previous adverse reaction to TZ or related compounds.
• Current use of TZ or concurrent use of DZ, AZ, prazosin, or tamsulosin.
• History of hepatic dysfunction.
• History of clinically relevant anemia.
• Secondary parkinsonism, drug-induced parkinsonism, Parkinson's-plus syndromes, or non-idiopathic PD.
• PD including use of more than two dopaminergic medications at screening.
• History of deep brain stimulation.
• Dementia per Movement Disorder Society Level 1 criteria.
• Traumatic brain injury or post-traumatic stress disorder.
• Presence of a confounding acute or unstable medical, psychiatric, or orthopedic condition.
• Unstable use of medications that modulate the central nervous system.
• Uncontrolled major depression or bipolar affective disorder, or other mental health disorders that are, in the opinion of the site investigator, sufficiently severe to increase risk of experiencing an Adverse Drug Reaction (ADR).
• Current suicidal ideation as measured by questions 4 or 5 of the Columbia-Suicide Severity Rating Scale.
• Participants with insufficient decisional capacity to provide written informed consent determined by the site investigator.
• Unstable use of antihypertensive medications.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nandakumar Narayanan

OTHER

Sponsor Role: lead

Responsible Party

Nandakumar Narayanan

Professor of Neurology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nandakumar Narayanan

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Central Contacts

Nandakumar Narayanan

Role: CONTACT

Phone: 319-356-2571

Email: nandakumar-narayanan@uiowa.edu

Heena Olalde

Role: CONTACT

Phone: 319-356-2571

Email: nandakumar-narayanan@uiowa.edu

References

Schultz JL, Gander PE, Workman CD, Ponto LL, Cross S, Nance CS, Groth CL, Taylor EB, Ernst SE, Xu J, Uc EY, Magnotta VA, Welsh MJ, Narayanan NS. A pilot dose-finding study of Terazosin in humans. medRxiv [Preprint]. 2024 May 22:2024.05.22.24307622. doi: 10.1101/2024.05.22.24307622.

Reference Type: BACKGROUND

PMID: 38826433 (View on PubMed)

Hart A, Aldridge G, Zhang Q, Narayanan NS, Simmering JE. Association of Terazosin, Doxazosin, or Alfuzosin Use and Risk of Dementia With Lewy Bodies in Men. Neurology. 2024 Jul 23;103(2):e209570. doi: 10.1212/WNL.0000000000209570. Epub 2024 Jun 19.

Reference Type: BACKGROUND

PMID: 38896813 (View on PubMed)

Schultz JL, Gander PE, Workman CD, Boles Ponto LL, Cross S, Nance CS, Groth CL, Taylor EB, Ernst SE, Xu J, Uc EY, Magnotta VA, Welsh MJ, Narayanan NS. A dose-finding study shows terazosin enhanced energy metabolism in neurologically healthy adults. J Parkinsons Dis. 2025 Nov;15(7):1253-1263. doi: 10.1177/1877718X251356503. Epub 2025 Aug 10.

Reference Type: BACKGROUND

PMID: 40785306 (View on PubMed)

Other Identifiers

TAMEPD

Identifier Type: -

Identifier Source: org_study_id