Terazosin for Dementia With Lewy Bodies

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Incidence of intervention-related adverse events between treatment arms [Time frame: 15 weeks]
• Frequency of drop-out/discontinuation of study intervention for any reason [Time frame: 15 weeks]
• Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy [Time frame: at baseline, 6 weeks and 15 weeks]

Secondary outcome measures (9)

• To assess the mean change in systolic and diastolic blood pressures [Time frame: at baseline, 6 weeks and 15 weeks]
• Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination [Time frame: at baseline, 6 weeks and 15 weeks]
• Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) [Time frame: at baseline, 6 weeks and 15 weeks]
• Montreal Cognitive Assessment [Time frame: at baseline, 6 weeks and 15 weeks]
• The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus) [Time frame: at baseline, 6 weeks and 15 weeks]
• Neuropsychiatric inventory [Time frame: at baseline, 6 weeks and 15 weeks]
• Fluorodeoxyglucose (FDG)-positron emission tomography (PET) [Time frame: at baseline, 6 weeks and 15 weeks]
• Serum ATP levels [Time frame: at baseline, 6 weeks and 15 weeks]
• Serum TeraZosin levels [Time frame: at baseline, 6 weeks and 15 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Iowa — Iowa City

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. PMID 31524631
• 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. PMID 33523098

Identifiers

NCT: NCT04760860 · 202101470

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗