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Terazosin for Dementia with Lewy Bodies

Phase 1
Not yet recruiting
Conditions
Dementia with Lewy Bodies
Interventions
Registration Number
NCT04760860
Lead Sponsor
Qiang Zhang
Brief 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.

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo Control ArmPlaceboParticipants 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.
Terazosin ArmTerazosin HydrochlorideParticipants 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.
Primary Outcome Measures
NameTimeMethod
Frequency of drop-out/discontinuation of study intervention for any reason15 weeks

The number of participants in each group who drop out of the study for any reason will be compared.

Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopyat baseline, 6 weeks and 15 weeks

Brain \[ATP\] as measured by 31P-Magnetic Resonance Spectroscopy

Incidence of intervention-related adverse events between treatment arms15 weeks

All patient-reported adverse events will be compared.

Secondary Outcome Measures
NameTimeMethod
Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examinationat baseline, 6 weeks and 15 weeks

Unified Parkinson Disease Rating Scale (UPDRS) part III will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks

Montreal Cognitive Assessmentat baseline, 6 weeks and 15 weeks

Montreal Cognitive Assessment

Neuropsychiatric inventoryat baseline, 6 weeks and 15 weeks

NPI will be evaluated at baseline and at 12 weeks

To assess the mean change in systolic and diastolic blood pressuresat baseline, 6 weeks and 15 weeks

Blood pressure will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks

Serum ATP levelsat baseline, 6 weeks and 15 weeks

Serum ATP level changes will be compared between the TZ and the placebo arms

Serum TeraZosin levelsat baseline, 6 weeks and 15 weeks

Serum Terazosin levels will be analyzed and a correlation between ATP levels and TZ levels will be evaluated

Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)at baseline, 6 weeks and 15 weeks

Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) will be evaluated at baseline and 12 weeks

The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus)at baseline, 6 weeks and 15 weeks

CIBIC-Plus will be evaluated at baseline and at 12 weeks

Fluorodeoxyglucose (FDG)-positron emission tomography (PET)at baseline, 6 weeks and 15 weeks

A surrogate for glucose metabolism in the brain

Trial Locations

Locations (1)

University of Iowa

🇺🇸

Iowa City, Iowa, United States

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