Terazosin for Dementia With Lewy Bodies (TZ-DLB)

• ClinicalTrials.gov Identifier: NCT04760860
• Recruitment Status: Not yet recruiting
• First Posted: February 18, 2021
• Last Update Posted: March 3, 2021
• Sponsor: Qiang Zhang
• Information provided by (Responsible Party): Qiang Zhang, University of Iowa

Tracking Information

• First Submitted Date: February 15, 2021
• First Posted Date: February 18, 2021
• Last Update Posted Date: March 3, 2021
• Estimated Study Start Date: October 2021
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2021)

• Incidence of intervention-related adverse events between treatment arms [ Time Frame: 15 weeks ]
  All patient-reported adverse events will be compared.
• 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

Original Primary Outcome Measures (submitted: February 15, 2021)

• Incidence of intervention-related adverse events between treatment arms [ Time Frame: 12 weeks ]
  All patient-reported adverse events will be compared.
• Frequency of drop-out/discontinuation of study intervention for any reason [ Time Frame: 12 weeks ]
  The number of participants in each group who drop out of the study for any reason will be compared.

Current Secondary Outcome Measures (submitted: February 26, 2021)

• To assess the mean change in systolic and diastolic blood pressures [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: at baseline, 6 weeks and 15 weeks ]
  Montreal Cognitive Assessment
• The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus) [ Time Frame: at baseline, 6 weeks and 15 weeks ]
  CIBIC-Plus will be evaluated at baseline and at 12 weeks
• Neuropsychiatric inventory [ Time Frame: at baseline, 6 weeks and 15 weeks ]
  NPI will be evaluated at baseline and at 12 weeks
• Fluorodeoxyglucose (FDG)-positron emission tomography (PET) [ Time Frame: at baseline, 6 weeks and 15 weeks ]
  A surrogate for glucose metabolism in the brain
• Serum ATP levels [ Time Frame: at baseline, 6 weeks and 15 weeks ]
  Serum ATP level changes will be compared between the TZ and the placebo arms
• Serum TeraZosin levels [ Time Frame: 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

Original Secondary Outcome Measures (submitted: February 15, 2021)

• To assess the mean change in systolic and diastolic blood pressures [ Time Frame: At baseline, 2 weeks, 6 weeks and 12 weeks ]
  Blood pressure will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks
• UPDRS Part III Motor examination [ Time Frame: At baseline, 2 weeks, 6 weeks and 12 weeks ]
  Unified Parkinson Disease Rating Scale (UPDRS) part III will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks
• ADAS-Cog [ Time Frame: At baseline and at 12 weeks ]
  Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) will be evaluated at baseline and 12 weeks
• MOCA [ Time Frame: At baseline, 2 weeks, 6 weeks and 12 weeks ]
  Montreal Cognitive Assessment
• The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus) [ Time Frame: At baseline and at 12 weeks ]
  CIBIC-Plus will be evaluated at baseline and at 12 weeks
• Neuropsychiatric inventory [ Time Frame: At baseline and at 12 weeks ]
  NPI will be evaluated at baseline and at 12 weeks
• MR spectroscopy p-31 [ Time Frame: At baseline and at 12 weeks ]
  A surrogate for brain ATP levels
• FDG-PET brain scan [ Time Frame: At baseline and at 12 weeks ]
  A surrogate for glucose metabolism in the brain
• Serum ATP levels [ Time Frame: At baseline, 2 weeks, 6 weeks and 12 weeks ]
  Serum ATP level changes will be compared between the TZ and the placebo arms
• Serum TZ levels [ Time Frame: At baseline, 2 weeks, 6 weeks and 12 weeks ]
  Serum Terazosin levels will be analyzed and a correlation between ATP levels and TZ levels will be evaluated

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Dementia With Lewy Bodies

Intervention

• Drug: 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.
  Other Name: Terazosin, Hytrin
• Other: Placebo
  In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks.

Study Arms

• Placebo Comparator: 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: Other: Placebo
• Experimental: 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: Drug: Terazosin Hydrochloride

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: February 26, 2021): 40
• Original Estimated Enrollment (submitted: February 15, 2021): 20
• Estimated Study Completion Date: October 2023
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Years to 90 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: qiang zhang, MD; 4154251369; qiang-zhang@uiowa.edu

Contact: Jordan Schultz, Pharm D; jordan-schultz@uiowa.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04760860
• Other Study ID Numbers: 202101470
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Upon reasonable request with justification for request from qualified researchers, anonymized data will be shared.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: One year after completion of this study
• Access Criteria: Qualified researchers may contact the PI of this study with reasonable requests for data to be shared. Inquiries must include what hypothesis the researcher intends to test using the shared data.

• Current Responsible Party: Qiang Zhang, University of Iowa
• Original Responsible Party: Same as current
• Current Study Sponsor: Qiang Zhang
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nandakumar Narayanan, MD, PhD; University of Iowa

• PRS Account: University of Iowa
• Verification Date: February 2021