Terazosin for Dementia With Lewy Bodies

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Terazosin Hydrochloride
  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.
• Другое Placebo
  In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks.

Первичные конечные точки

• Incidence of intervention-related adverse events between treatment arms [Срок оценки: 15 weeks]
• Frequency of drop-out/discontinuation of study intervention for any reason [Срок оценки: 15 weeks]
• Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy [Срок оценки: at baseline, 6 weeks and 15 weeks]

Вторичные конечные точки (9)

• To assess the mean change in systolic and diastolic blood pressures [Срок оценки: at baseline, 6 weeks and 15 weeks]
• Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination [Срок оценки: at baseline, 6 weeks and 15 weeks]
• Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) [Срок оценки: at baseline, 6 weeks and 15 weeks]
• Montreal Cognitive Assessment [Срок оценки: at baseline, 6 weeks and 15 weeks]
• The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus) [Срок оценки: at baseline, 6 weeks and 15 weeks]
• Neuropsychiatric inventory [Срок оценки: at baseline, 6 weeks and 15 weeks]
• Fluorodeoxyglucose (FDG)-positron emission tomography (PET) [Срок оценки: at baseline, 6 weeks and 15 weeks]
• Serum ATP levels [Срок оценки: at baseline, 6 weeks and 15 weeks]
• Serum TeraZosin levels [Срок оценки: at baseline, 6 weeks and 15 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Iowa — Iowa City

Публикации

• 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. PMID 31524631
• 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. PMID 33523098

Идентификаторы

NCT: NCT04760860 · 202101470

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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