Terazosin for Dementia With Lewy Bodies (TZ-DLB)

a Randomized, Double Blind, Placebo Controlled Clinical Trial Exploring the Target Engagement and Tolerability of Terazosin Hydrochloride in Patients With Dementia With Lewy Bodies

The TZ-DLB trial will be a 3:2 (active:placebo) randomized, double-blind, placebo-controlled Pilot trial to evaluate the tolerability of terazosin for the treatment of dementia with Lewy bodies.

Study Overview

• Status: Not yet recruiting
• Conditions: Dementia With Lewy Bodies
• Intervention / Treatment: Other: Placebo; Drug: Terazosin Hydrochloride

Detailed Description

This will be a single center, randomized, double-blind, placebo-controlled, pilot study to assess the tolerability of terazosin (TZ) at 1 and 5 milligrams (MG) daily for patients with DLB. The primary goal of this study is to assess the tolerability of TZ in patients with DLB. 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 DLB. 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 DLB.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: qiang zhang, MD; Phone Number: 4154251369; Email: qiang-zhang@uiowa.edu
• Study Contact Backup: Name: Jordan Schultz, Pharm D; Email: jordan-schultz@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52252
      • University of Iowa
      • Contact: qiang zhang, MD; Email: qiang-zhang@uiowa.edu
      • Contact: Jordan Schultz, PharmD; Email: jordan-schultz@uiowa.edu
      • Principal Investigator: Nandakumar Narayanan, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 88 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women with the diagnosis of dementia with Lewy Bodies per 2017 DLB Consortium criteria.
• Baseline MOCA 18 or above. On stable AChEI and/or memantine treatment regimen for ≥4 weeks prior to baseline.

Exclusion Criteria:

• Subjects unwilling or unable to give informed consent
• 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.
• Orthostatic hypotension defined as symptomatic decrease in BP > 20mmHg systolic or > 10mmHg diastolic on supine to sitting or standing, or a sitting blood pressure of ≤90/60.
• Clinically significant traumatic brain injury or post-traumatic stress disorder
• Presence of other known medical comorbidities that in the investigator's opinion would compromise participation in the study
• Psychiatric comorbidities including major depression, bipolar affective disorder, or other mental health disorders that are sufficiently severe to increase adverse event risk or impact neurology 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.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Control Arm; Participants in this arm will receive placebo during the trial for 15 weeks, the placebo will follow the same schedule as the Terazosin group; the placebo capsules will have the same appearance as the Terazosin capsules.	Other: Placebo; In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks.
Experimental: Terazosin Arm; Participants in this arm will receive Terazosin during the trial for 15 weeks. Participants will start at 1mg daily for the first 6 week, then the dosage will be increased to 5mg daily over 3 weeks, and continued for the last 6 weeks.	Drug: Terazosin Hydrochloride; In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the Terazosin group will receive Terazosin hydrochloride treatment for 15 weeks. Participants will start at 1mg daily for the first 6 week, then the dosage will be increased to 5mg daily over 3 weeks, and continued for the last 6 weeks.; Other Names: Terazosin, Hytrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of intervention-related adverse events between treatment arms	All patient-reported adverse events will be compared.	15 weeks
Frequency of drop-out/discontinuation of study intervention for any reason	The number of participants in each group who drop out of the study for any reason will be compared.	15 weeks
Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy	Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy	at baseline, 6 weeks and 15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the mean change in systolic and diastolic blood pressures	Blood pressure will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks	at baseline, 6 weeks and 15 weeks
Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination	Unified Parkinson Disease Rating Scale (UPDRS) part III will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks	at baseline, 6 weeks and 15 weeks
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)	Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) will be evaluated at baseline and 12 weeks	at baseline, 6 weeks and 15 weeks
Montreal Cognitive Assessment	Montreal Cognitive Assessment	at baseline, 6 weeks and 15 weeks
The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus)	CIBIC-Plus will be evaluated at baseline and at 12 weeks	at baseline, 6 weeks and 15 weeks
Neuropsychiatric inventory	NPI will be evaluated at baseline and at 12 weeks	at baseline, 6 weeks and 15 weeks
Fluorodeoxyglucose (FDG)-positron emission tomography (PET)	A surrogate for glucose metabolism in the brain	at baseline, 6 weeks and 15 weeks
Serum ATP levels	Serum ATP level changes will be compared between the TZ and the placebo arms	at baseline, 6 weeks and 15 weeks
Serum TeraZosin levels	Serum Terazosin levels will be analyzed and a correlation between ATP levels and TZ levels will be evaluated	at baseline, 6 weeks and 15 weeks

Collaborators and Investigators

• Sponsor: Qiang Zhang
• Investigators: Principal Investigator: Nandakumar Narayanan, MD, PhD, University of Iowa

Publications and helpful links

General Publications

• Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L. Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases. J Clin Invest. 2019 Oct 1;129(10):4539-4549. doi: 10.1172/JCI129987.
• Simmering JE, Welsh MJ, Liu L, Narayanan NS, Pottegard A. Association of Glycolysis-Enhancing alpha-1 Blockers With Risk of Developing Parkinson Disease. JAMA Neurol. 2021 Apr 1;78(4):407-413. doi: 10.1001/jamaneurol.2020.5157.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2024
• Primary Completion (Anticipated): October 1, 2026
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: February 15, 2021
• First Submitted That Met QC Criteria: February 15, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Lewy Body Disease; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Prazosin; Terazosin
• Other Study ID Numbers: 202101470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request with justification for request from qualified researchers, anonymized data will be shared.
• IPD Sharing Time Frame: One year after completion of this study
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes