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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo Control Arm | Placebo Comparator | 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. |
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| Terazosin Arm | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Terazosin Hydrochloride | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of intervention-related adverse events between treatment arms | All patient-reported adverse events will be compared. | 15 weeks |
| 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. | 15 weeks |
| Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy | Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy | at baseline, 6 weeks and 15 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | at baseline, 6 weeks and 15 weeks |
| Unified Parkinson Disease Rating Scale (UPDRS) part III Motor examination |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| qiang zhang, MD | Contact | 4154251369 | qiang-zhang@uiowa.edu | |
| Jordan Schultz, Pharm D | Contact | jordan-schultz@uiowa.edu |
| Name | Affiliation | Role |
|---|---|---|
| Nandakumar Narayanan, MD, PhD | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Iowa City | Iowa | 52252 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31524631 | Background | 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. | |
| 33523098 |
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Upon reasonable request with justification for request from qualified researchers, anonymized data will be shared.
One year after completion of this study
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.
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| ID | Term |
|---|---|
| D020961 | Lewy Body Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C041226 | Terazosin |
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| Placebo | Other | In this double blind, randomized, placebo controlled phase I clinical trial, subjects randomized into the control group will receive placebo for 15 weeks. |
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Unified Parkinson Disease Rating Scale (UPDRS) part III will be evaluated at baseline, 2 weeks, 6 weeks and 12 weeks |
| at baseline, 6 weeks and 15 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 | at baseline, 6 weeks and 15 weeks |
| Montreal Cognitive Assessment | Montreal Cognitive Assessment | at baseline, 6 weeks and 15 weeks |
| The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus) | CIBIC-Plus will be evaluated at baseline and at 12 weeks | at baseline, 6 weeks and 15 weeks |
| Neuropsychiatric inventory | NPI will be evaluated at baseline and at 12 weeks | at baseline, 6 weeks and 15 weeks |
| Fluorodeoxyglucose (FDG)-positron emission tomography (PET) | A surrogate for glucose metabolism in the brain | at baseline, 6 weeks and 15 weeks |
| Serum ATP levels | Serum ATP level changes will be compared between the TZ and the placebo arms | at baseline, 6 weeks and 15 weeks |
| Serum TeraZosin levels | Serum Terazosin levels will be analyzed and a correlation between ATP levels and TZ levels will be evaluated | at baseline, 6 weeks and 15 weeks |
| 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. |
| D009422 | Nervous System Diseases |
| D003704 | Dementia |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |