Clinical trial NCT04760860: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Dementia With Lewy Bodies
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2021-02-18
Enrollment: 40
Sex: ALL
Minimum age (years): 0
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of intervention-related adverse events between treatment arms
timeFrame: 15 weeks
measure: Frequency of drop-out/discontinuation of study intervention for any reason
timeFrame: 15 weeks
measure: Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy
timeFrame: at baseline, 6 weeks and 15 weeks
Secondary outcomes:
measure: To assess the mean change in systolic and diastolic blood pressures
timeFrame: at baseline, 6 weeks and 15 weeks
measure: Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination
timeFrame: at baseline, 6 weeks and 15 weeks
measure: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
timeFrame: at baseline, 6 weeks and 15 weeks
measure: Montreal Cognitive Assessment
timeFrame: at baseline, 6 weeks and 15 weeks
measure: The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus)
timeFrame: at baseline, 6 weeks and 15 weeks
measure: Neuropsychiatric inventory
timeFrame: at baseline, 6 weeks and 15 weeks
measure: Fluorodeoxyglucose (FDG)-positron emission tomography (PET)
timeFrame: at baseline, 6 weeks and 15 weeks
measure: Serum ATP levels
timeFrame: at baseline, 6 weeks and 15 weeks
measure: Serum TeraZosin levels
timeFrame: at baseline, 6 weeks and 15 weeks
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
affiliation: University of Iowa
name: Nandakumar Narayanan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.