Back to resultsTerazosin for Dementia With Lewy Bodies (TZ-DLB)
Primary Purpose
Dementia With Lewy Bodies
Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Terazosin Hydrochloride
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Dementia With Lewy Bodies
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
Sites / Locations
- University of Iowa
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo Control Arm
Terazosin Arm
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Incidence of intervention-related adverse events between treatment arms
All patient-reported adverse events will be compared.
Frequency of drop-out/discontinuation of study intervention for any reason
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
Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy
Secondary Outcome Measures
To assess the mean change in systolic and diastolic blood pressures
Blood pressure will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks
Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination
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)
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) will be evaluated at baseline and 12 weeks
Montreal Cognitive Assessment
Montreal Cognitive Assessment
The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus)
CIBIC-Plus will be evaluated at baseline and at 12 weeks
Neuropsychiatric inventory
NPI will be evaluated at baseline and at 12 weeks
Fluorodeoxyglucose (FDG)-positron emission tomography (PET)
A surrogate for glucose metabolism in the brain
Serum ATP levels
Serum ATP level changes will be compared between the TZ and the placebo arms
Serum TeraZosin levels
Serum Terazosin levels will be analyzed and a correlation between ATP levels and TZ levels will be evaluated
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04760860
Brief Title
Terazosin for Dementia With Lewy Bodies
Acronym
TZ-DLB
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2024 (Anticipated)
Primary Completion Date
October 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Qiang Zhang
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dementia With Lewy Bodies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo Control Arm
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Terazosin Arm
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Terazosin Hydrochloride
Other Intervention Name(s)
Terazosin, Hytrin
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks.
Primary Outcome Measure Information:
Title
Incidence of intervention-related adverse events between treatment arms
Description
All patient-reported adverse events will be compared.
Time Frame
15 weeks
Title
Frequency of drop-out/discontinuation of study intervention for any reason
Description
The number of participants in each group who drop out of the study for any reason will be compared.
Time Frame
15 weeks
Title
Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy
Description
Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy
Time Frame
at baseline, 6 weeks and 15 weeks
Secondary Outcome Measure Information:
Title
To assess the mean change in systolic and diastolic blood pressures
Description
Blood pressure will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks
Time Frame
at baseline, 6 weeks and 15 weeks
Title
Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination
Description
Unified Parkinson Disease Rating Scale (UPDRS) part III will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks
Time Frame
at baseline, 6 weeks and 15 weeks
Title
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Description
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) will be evaluated at baseline and 12 weeks
Time Frame
at baseline, 6 weeks and 15 weeks
Title
Montreal Cognitive Assessment
Description
Montreal Cognitive Assessment
Time Frame
at baseline, 6 weeks and 15 weeks
Title
The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus)
Description
CIBIC-Plus will be evaluated at baseline and at 12 weeks
Time Frame
at baseline, 6 weeks and 15 weeks
Title
Neuropsychiatric inventory
Description
NPI will be evaluated at baseline and at 12 weeks
Time Frame
at baseline, 6 weeks and 15 weeks
Title
Fluorodeoxyglucose (FDG)-positron emission tomography (PET)
Description
A surrogate for glucose metabolism in the brain
Time Frame
at baseline, 6 weeks and 15 weeks
Title
Serum ATP levels
Description
Serum ATP level changes will be compared between the TZ and the placebo arms
Time Frame
at baseline, 6 weeks and 15 weeks
Title
Serum TeraZosin levels
Description
Serum Terazosin levels will be analyzed and a correlation between ATP levels and TZ levels will be evaluated
Time Frame
at baseline, 6 weeks and 15 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
qiang zhang, MD
Phone
4154251369
Email
qiang-zhang@uiowa.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Jordan Schultz, Pharm D
Email
jordan-schultz@uiowa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nandakumar Narayanan, MD, PhD
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52252
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
qiang zhang, MD
Email
qiang-zhang@uiowa.edu
First Name & Middle Initial & Last Name & Degree
Jordan Schultz, PharmD
Email
jordan-schultz@uiowa.edu
First Name & Middle Initial & Last Name & Degree
Nandakumar Narayanan, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Upon reasonable request with justification for request from qualified researchers, anonymized data will be shared.
IPD Sharing Time Frame
One year after completion of this study
IPD Sharing 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.
Citations:
PubMed Identifier
31524631
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.
Results Reference
background
PubMed Identifier
33523098
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.
Results Reference
background
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Terazosin for Dementia With Lewy Bodies
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