Dementia With Lewy Bodies
Conditions
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.
Interventions
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.
OTHERPlacebo
In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks.
Sponsors
Qiang Zhang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
0 Years to 90 Years
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 ≤90/60. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of intervention-related adverse events between treatment arms | 15 weeks | All patient-reported adverse events will be compared. |
| Frequency of drop-out/discontinuation of study intervention for any reason | 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 | at baseline, 6 weeks and 15 weeks | Brain \[ATP\] as measured by 31P-Magnetic Resonance Spectroscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the mean change in systolic and diastolic blood pressures | at baseline, 6 weeks and 15 weeks | Blood pressure will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks |
| Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination | at 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 |
| 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 |
| Montreal Cognitive Assessment | at baseline, 6 weeks and 15 weeks | Montreal Cognitive Assessment |
| 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 |
| Neuropsychiatric inventory | at baseline, 6 weeks and 15 weeks | NPI 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 |
| Serum ATP levels | at baseline, 6 weeks and 15 weeks | Serum ATP level changes will be compared between the TZ and the placebo arms |
| Serum TeraZosin levels | at baseline, 6 weeks and 15 weeks | Serum Terazosin levels will be analyzed and a correlation between ATP levels and TZ levels will be evaluated |
Countries
United States
Contacts
CONTACTqiang zhang, MD
CONTACTJordan Schultz, Pharm D
PRINCIPAL_INVESTIGATORNandakumar Narayanan, MD, PhD
University of Iowa
Outcome results
None listed