Terazosin for Dementia With Lewy Bodies

Dementia With Lewy Bodies Clinical Trial

— TZ-DLB  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04760860
• Other study ID #: 202101470
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 2024
• Est. completion date: December 2026

Study information

• Verified date: May 2024
• Source: University of Iowa
• Contact: qiang zhang, MD
• Phone: 4154251369
• Email: qiang-zhang[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Dementia
• Dementia With Lewy Bodies
• Lewy Body Disease

Intervention

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:
• Placebo
In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks.

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Qiang Zhang

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of intervention-related adverse events between treatment arms	All patient-reported adverse events will be compared.	15 weeks
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Montreal Cognitive Assessment	Montreal Cognitive Assessment	at baseline, 6 weeks and 15 weeks
Secondary	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
Secondary	Neuropsychiatric inventory	NPI will be evaluated at baseline and at 12 weeks	at baseline, 6 weeks and 15 weeks
Secondary	Fluorodeoxyglucose (FDG)-positron emission tomography (PET)	A surrogate for glucose metabolism in the brain	at baseline, 6 weeks and 15 weeks
Secondary	Serum ATP levels	Serum ATP level changes will be compared between the TZ and the placebo arms	at baseline, 6 weeks and 15 weeks
Secondary	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