What side effects are associated with this type of intervention?

Common treatments for dementia, such as serotonergic medications (e.g., SSRIs like citalopram) and alpha-adrenergic receptor blockers (e.g., prazosin), have various side effects. Serotonergic medications can cause paradoxical behavioral reactions, extrapyramidal side effects, confusion, and sedation. Alpha-adrenergic receptor blockers like prazosin may lead to hypotension, dizziness, and rebound hypertension if discontinued abruptly. Antipsychotics, often used for behavioral symptoms, can result in sedation, confusion, and extrapyramidal symptoms. It is crucial to start with low doses and monitor patients closely to mitigate these adverse effects.

What prior FDA approvals exist?

The FDA has approved several medications for the treatment of dementia, primarily focusing on Alzheimer's disease. These include cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and an NMDA receptor antagonist, memantine. While these drugs do not fall into the category of Alpha-1 Adrenergic Receptor Antagonists like Terazosin, they are the mainstay of current dementia treatment. There is ongoing research into other potential treatments, including those targeting different pathways, such as serotonin receptors and tau aggregation inhibitors.

What other types of research exist?

Promising novel alternatives to Terazosin for dementia patients include ORM-12741, a selective alpha-2C adrenoceptor antagonist, which has shown potential in improving episodic memory in Alzheimer's disease patients. Additionally, muscarinic agonists and antiamyloid substances are being tested in clinical trials and may offer new therapeutic options. Growth factors, particularly nerve growth factor (NGF), are also under preclinical evaluation and hold promise for future treatments.

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Alpha-1 Adrenergic Blocker

Terazosin for Lewy Body Dementia (TZ-DLB Trial)

Phase 1 & 2

Waitlist Available

Led By Nandakumar Narayanan, MD, PhD

Research Sponsored by Qiang Zhang

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Men or women with the diagnosis of dementia with Lewy Bodies per 2017 DLB Consortium criteria

Baseline MOCA 18 or above

Must not have

Use of doxazosin, alfuzosin, prazosin, or tamsulosin

Participant is restricted from traveling to and from the study site

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at baseline, 6 weeks and 15 weeks

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

Summary

This trial is testing if a medication called terazosin can be tolerated by people with a specific type of dementia called dementia with Lewy bodies. The goal is to see if the medication helps the body make and use energy better, which could help these patients. The results will guide future studies on this and similar medications.

Who is the study for?

This trial is for men and women diagnosed with dementia with Lewy bodies who are on a stable treatment of AChEI/memantine for at least 4 weeks, have a MOCA score of 18 or above, and meet specific diagnostic criteria. Excluded are those with serious medical conditions, unstable psychiatric disorders, recent use of investigational drugs or certain CNS medications, pregnant women or those planning to become pregnant during the study.

What is being tested?

The TZ-DLB trial is testing the tolerability of terazosin hydrochloride compared to a placebo in treating dementia with Lewy bodies. Participants will be randomly assigned in a ratio of 3:2 to either receive terazosin or placebo in this double-blind study where neither they nor the researchers know who gets which treatment.

What are the potential side effects?

Potential side effects from terazosin may include dizziness due to low blood pressure (orthostatic hypotension), fatigue, nasal congestion, headache, and weakness. Since it's being tested against a placebo which has no active ingredients, any side effects would be compared between the two groups.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with dementia with Lewy Bodies.

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My mental function test score is 18 or higher.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently taking medication for prostate issues or high blood pressure.

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I cannot travel to the study site.

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I do not have any severe or unstable health conditions.

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I am not pregnant and do not plan to become pregnant during the study.

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I experience significant drops in blood pressure when standing up.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at baseline, 6 weeks and 15 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at baseline, 6 weeks and 15 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and at baseline, 6 weeks and 15 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Brain [ATP] as measured by 31P-Magnetic Resonance Spectroscopy

Frequency of drop-out/discontinuation of study intervention for any reason

Incidence of intervention-related adverse events between treatment arms

Secondary study objectives

Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)

Fluorodeoxyglucose (FDG)-positron emission tomography (PET)

Montreal Cognitive Assessment

+6 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Terazosin ArmExperimental Treatment1 Intervention

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.

Group II: Placebo Control ArmPlacebo Group1 Intervention

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.

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for dementia include cholinesterase inhibitors (e.g., donepezil, rivastigmine), which work by increasing acetylcholine levels in the brain to improve cognitive function, and NMDA receptor antagonists (e.g., memantine), which regulate glutamate activity to protect neurons from excitotoxicity. Antipsychotic agents (e.g., pimavanserin) are used to manage neuropsychiatric symptoms by modulating serotonin and dopamine receptors. Alpha-1 adrenergic receptor antagonists, such as Terazosin, are being studied for their potential to improve blood flow and reduce neuroinflammation, which may help alleviate cognitive and neuropsychiatric symptoms in dementia patients. Understanding these mechanisms is crucial for tailoring treatments to individual patient needs and improving overall outcomes.

Recent advances in the management of neuropsychiatric symptoms in dementia.Effect of galantamine on verbal repetition in AD: a secondary analysis of the VISTA trial.