Terazosin for Dementia With Lewy Bodies

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Dementia With Lewy Bodies

Intervention / Treatment
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* Drug: Terazosin Hydrochloride
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Control Arm<br>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<br>* In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks.<br>|
| Experimental: Terazosin Arm<br>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<br>* 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.<br>* Other names: Terazosin, Hytrin;|

What is the study measuring?
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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 |