a Randomized, Double Blind, Placebo Controlled Clinical Trial Exploring the Target Engagement and Tolerability of Terazosin Hydrochloride in Patients With Dementia With Lewy Bodies
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Frequency of drop-out/discontinuation of study intervention for any reason
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 0 Years to 90 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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/
- •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
Arms & Interventions
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.
Intervention: Placebo (Other)
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.
Intervention: Terazosin Hydrochloride (Drug)
Outcomes
Primary Outcomes
Frequency of drop-out/discontinuation of study intervention for any reason
Time Frame: 15 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 Spectroscopy
Time Frame: at baseline, 6 weeks and 15 weeks
Brain \[ATP\] as measured by 31P-Magnetic Resonance Spectroscopy
Incidence of intervention-related adverse events between treatment arms
Time Frame: 15 weeks
All patient-reported adverse events will be compared.
Secondary Outcomes
- Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination(at baseline, 6 weeks and 15 weeks)
- Montreal Cognitive Assessment(at baseline, 6 weeks and 15 weeks)
- Neuropsychiatric inventory(at baseline, 6 weeks and 15 weeks)
- To assess the mean change in systolic and diastolic blood pressures(at baseline, 6 weeks and 15 weeks)
- Serum ATP levels(at baseline, 6 weeks and 15 weeks)
- Serum TeraZosin levels(at baseline, 6 weeks and 15 weeks)
- Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)(at baseline, 6 weeks and 15 weeks)
- The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus)(at baseline, 6 weeks and 15 weeks)
- Fluorodeoxyglucose (FDG)-positron emission tomography (PET)(at baseline, 6 weeks and 15 weeks)
Investigators
Qiang Zhang
Associate of Neurology
University of Iowa