Terazosin And Metabolic Engagement in Parkinson's Disease

NCT07288450 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: TAMEPD
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Whole-blood ATP

  Changes in the amount of ATP in the blood for patients taking Terazosin vs. Placebo.

  1 year

Study Arms (2)

Active arm

EXPERIMENTAL

Terazosin hydrochloride

Drug: Terazosin Hydrochloride

Placebo

PLACEBO COMPARATOR

Placebo control

Other: Placebo

Interventions

Terazosin Hydrochloride DRUG

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

Active arm

Placebo OTHER

Placebo control for Terazosin

Placebo

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nandakumar Narayanan: lead

Related Publications (3)

• 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.

  PMID: 38826433 BACKGROUND

• 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.

  PMID: 38896813 BACKGROUND

• 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.

  PMID: 40785306 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Terazosin

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Nandakumar Narayanan

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nandakumar Narayanan

CONTACT

319-356-2571; nandakumar-narayanan@uiowa.edu

Heena Olalde

CONTACT

319-356-2571; nandakumar-narayanan@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: The primary goal of this study is to assess target engagement of TZ at varying doses of TZ. Specifically, we wish to identify a dose of TZ that provides optimal pharmacodynamic effect in patients with PD and to determine if this effect can be sustained for 6 months. By incorporating multiple assays of target engagement during a slow titration of TZ, we will be able to efficiently study target engagement at multiple doses using a multi-modal approach. We will also be able to assess the relationship between target engagement in the brain and the blood assays.

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 17, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2031
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD will be available on publication.
• Access Criteria: IPD will be available to the general public via OpenNeuro.org