Terazosin for Early Parkinson's Disease

Recruiting at 1 trial location

Overseen By MaryClare Kelly

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Alpha blockers, PDE5 inhibitors

Disqualifiers: Dementia, Severe depression, Hypertension, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 26 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests terazosin, a medication that may aid individuals with early Parkinson's disease by improving heart-related symptoms that often precede motor symptoms. Researchers aim to determine if terazosin can produce changes detectable through specific heart imaging. Ideal candidates for this trial include those diagnosed with REM sleep behavior disorder, a condition where individuals act out dreams, and who experience issues like a reduced sense of smell or changes in color vision. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using alpha-adrenergic antagonists or certain medications like sildenafil, tadalafil, or vardenafil.

Is there any evidence suggesting that terazosin is likely to be safe for humans?

Research has shown that terazosin is considered safe due to its previous use for other purposes. In earlier studies, people taking 5 mg of terazosin daily did not experience major side effects, indicating that the treatment is generally well-tolerated. While side effects can occur, they are often mild. The trial will gradually increase the dosage to help ensure participants tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's disease?

Unlike the standard Parkinson's treatments like levodopa or dopamine agonists, Terazosin is unique because it targets energy production in cells, which might protect nerve cells from dying. Researchers are excited about this because Terazosin, originally used for treating high blood pressure, may offer a new approach by boosting cell energy levels and possibly slowing disease progression. Additionally, its oral administration and adjustable dosage make it user-friendly, potentially enhancing patient adherence and outcomes.

What evidence suggests that terazosin might be an effective treatment for early Parkinson's disease?

Research suggests that terazosin, which participants in this trial will receive, might help with Parkinson's disease by protecting nerve cells. Studies have shown that terazosin can improve movement and increase energy in the brain, potentially slowing the progression of Parkinson's symptoms. Early research and reviews of human data support these findings, indicating its potential to protect the brain. Although more research is needed, these results are promising for those at risk of developing Parkinson's. ^{2 3 5 6 7}

Who Is on the Research Team?

Michele L Tagliati, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for people aged 50-85 with early signs of Parkinson's Disease, like REM Sleep Behavior Disorder or loss of smell. They must have constipation and may have depression but can't be severely depressed or demented. Participants need a specific heart scan result and can't have other serious health issues like recent heart attacks, very low blood pressure, severe sleep apnea, or diabetes.

Inclusion Criteria

I have been diagnosed with a specific sleep disorder related to dreaming.

I have been diagnosed with a specific sleep disorder involving acting out dreams.

I have at least one of the following: reduced sense of smell, constipation, color vision issues, depression, or abnormal heart scan.

Exclusion Criteria

I have Parkinson's disease symptoms not caused by primary Parkinson's.

You have a condition called dementia, as determined by a test score lower than 22 on the MOCA.

I have severe depression with a BDI score over 13.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral doses of adrenergic blocker terazosin, titrated from 1 mg to 5 mg or 10 mg based on tolerability

26 weeks

Weekly visits for dose titration, followed by regular monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including heart rate variability and MIBG reuptake

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Terazosin

Trial Overview

The study tests Terazosin's effect on the hearts of those at risk for Parkinson's. It looks at how this blood pressure medication might influence certain heart-related changes seen in early Parkinson’s stages by using special imaging techniques and comparing them to symptoms severity.

How Is the Trial Designed?

Group I: terazosin therapy Experimental Treatment 1 Intervention

Daily oral doses of adrenergic blocker 5 mg or 10 mg. The dosage will be gradually increased from the initial recommended starting dose of 1 mg daily at bedtime and titrated stepwise to 2mg, 5mg or 10 mg weekly, according to patient tolerability, as measured by subjective complaints, arterial blood pressure and heart rate. The target dose will be 5 mg or 10 mg daily based on subject's tolerability.

Terazosin is already approved in United States for the following indications:

Approved in United States as Hytrin for:

• Benign prostatic hyperplasia (enlarged prostate)
• Hypertension (high blood pressure)

Approved in United States as Tezruly for:

• Benign prostatic hyperplasia (enlarged prostate)
• Hypertension (high blood pressure)

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Published Research Related to This Trial

The combination of eltoprazine and preladenant with low-dose l-dopa effectively reduced dyskinetic-like behavior in animal models of Parkinson's disease without impairing the motor benefits of l-dopa, suggesting a potential new treatment strategy.

In both rat and monkey models, this combination therapy not only prevented worsening of motor performance but also maintained the therapeutic effects of l-dopa, indicating its efficacy in managing both dyskinesia and motor symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidyskinetic effect of A2A and 5HT1A/1B receptor ligands in two animal models of Parkinson's disease. Pinna, A., Ko, WK., Costa, G., et al.[2017]

The novel 5-HT1A receptor biased agonist F13714 effectively abolished L-DOPA-induced dyskinesia (LID) in hemiparkinsonian rats at very low doses, suggesting a strong potential for reducing dyskinesia in Parkinson's disease treatment.

F13714's effects were linked to its ability to inhibit serotonin release while slightly increasing dopamine release, indicating that targeting 5-HT1A autoreceptors may offer a promising strategy for improving L-DOPA therapy in Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of serotonin 5-HT(1A) receptor 'biased agonists' in rat models of Parkinson's disease and L-DOPA-induced dyskinesia. Iderberg, H., McCreary, AC., Varney, MA., et al.[2015]

EMD-281,014, a selective serotonin 2A receptor antagonist, was found to be well-tolerated in parkinsonian rats and did not interfere with the anti-parkinsonian effects of L-DOPA.

However, EMD-281,014 did not significantly reduce the severity of L-DOPA-induced abnormal involuntary movements (AIMs) in these rats, indicating potential differences in treatment responses between rodent and primate models of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the selective 5-HT2A receptor antagonist EMD-281,014 on L-DOPA-induced abnormal involuntary movements in the 6-OHDA-lesioned rat. Frouni, I., Kwan, C., Bédard, D., et al.[2020]

In a study involving monkeys treated with a neurotoxin to induce Parkinson's-like symptoms, the metabotropic glutamate receptor 5 antagonist, 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine, significantly protected against the loss of dopaminergic and noradrenergic neurons, suggesting a potential therapeutic strategy for Parkinson's disease.

After 21 weeks, monkeys treated with the antagonist showed no significant parkinsonian symptoms and had higher levels of dopamine transporter and tyrosine hydroxylase, indicating preserved neuronal function compared to those receiving a vehicle treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabotropic glutamate receptor 5 antagonist protects dopaminergic and noradrenergic neurons from degeneration in MPTP-treated monkeys. Masilamoni, GJ., Bogenpohl, JW., Alagille, D., et al.[2023]

In a small study of 5 patients with Parkinson's disease, tegaserod, a medication that stimulates gastrointestinal motility, was well tolerated and led to improvements in bowel movement frequency and stool consistency.

Despite existing treatments for constipation in Parkinson's disease, tegaserod shows promise as an effective option, suggesting that further research is needed to explore its benefits in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tegaserod in constipation associated with Parkinson disease. Morgan, JC., Sethi, KD.[2012]

In a 12-week randomized trial involving 172 patients with early-stage Parkinson's disease, transdermal rotigotine significantly improved daily living and motor function scores compared to placebo, with a mean change of -8.4 in the rotigotine group versus -4.1 in the placebo group.

Rotigotine was well tolerated at doses up to 16 mg/24 hours, with no serious drug-related adverse events reported, indicating its safety for use in early-stage Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal rotigotine in early stage Parkinson's disease: a randomized, double-blind, placebo-controlled trial. Mizuno, Y., Nomoto, M., Kondo, T., et al.[2017]

Terazosin is a selective alpha 1-adrenoceptor blocker that effectively lowers blood pressure and can be taken once daily due to its long half-life, making it convenient for patients with mild-to-moderate hypertension.

It has a significant advantage over prazosin due to its greater water solubility and longer duration of action, and it is safe to use in combination with other antihypertensive medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Terazosin: a new alpha adrenoceptor blocking drug. Achari, R., Laddu, A.[2019]

In a pilot study involving 15 patients with benign prostatic hyperplasia (BPH), terazosin significantly improved both peak and mean urine flow rates, as well as reduced residual urine volume and obstructive symptoms (p < 0.001).

These preliminary results suggest that terazosin is an effective treatment option for alleviating symptoms associated with BPH, supporting its therapeutic value in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of terazosin in the treatment of benign prostatic hyperplasia. A pilot study. Dunzendorfer, U.[2013]

In a 6-month study comparing terazosin and enalapril, both antihypertensive medications showed similar effectiveness, with about 60% of patients continuing their prescriptions.

The differences in prescribing patterns were influenced more by marketing strategies and physician perceptions than by any significant clinical differences between the two drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing and usage patterns of two antihypertensive agents: a comparison of terazosin and enalapril. Toiber, F., Murthy, VS.[2015]

In a study involving post-mortem brain samples from 14 Parkinson's disease patients and 20 monkeys, increased binding of the 5-HT1B receptor was found in L-DOPA-treated monkeys with dyskinesias, suggesting a link between this receptor and the development of abnormal movements.

The findings indicate that normalizing 5-HT1B receptor levels may help manage motor complications in Parkinson's disease, highlighting its potential as a therapeutic target for reducing L-DOPA-induced dyskinesias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contribution of brain serotonin subtype 1B receptors in levodopa-induced motor complications. Morin, N., Morissette, M., Grégoire, L., et al.[2016]

Rotigotine transdermal patches significantly improve symptoms of Parkinson's disease, as shown by greater reductions in Unified Parkinson's Disease Rating Scale scores in a meta-analysis of six trials involving 1789 patients.

While effective, rotigotine is associated with a higher rate of adverse events, including application site reactions and vomiting, indicating that while it helps manage symptoms, patients may experience more side effects compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rotigotine transdermal patch in Parkinson's disease: a systematic review and meta-analysis. Zhou, CQ., Li, SS., Chen, ZM., et al.[2021]

Sarizotan significantly reduced immobility in a forced swim test, indicating potential antidepressant-like effects in a rat model of Parkinson's disease, without affecting anxiety-like behaviors.

The treatment also promoted cell proliferation in brain regions associated with mood regulation, suggesting that sarizotan may have restorative properties alongside its antidyskinetic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant-like properties of sarizotan in experimental Parkinsonism. Zhang, X., Egeland, M., Svenningsson, P.[2021]

In a phase I/IIa study involving 22 patients with Parkinson's disease, a single dose of eltoprazine significantly reduced L-DOPA-induced dyskinesias without affecting normal motor responses to L-DOPA, indicating its potential as an effective treatment.

Eltoprazine was well tolerated at all tested doses (2.5, 5, and 7.5 mg), with the most common side effects being nausea and dizziness, suggesting a favorable safety profile for further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson's disease: a dose-finding study. Svenningsson, P., Rosenblad, C., Af Edholm Arvidsson, K., et al.[2018]

In a study of 21 normotensive spinal cord injured patients, terazosin significantly reduced the severity and frequency of autonomic dysreflexia over a 3-month period, with improvements noted as early as one week after treatment.

Terazosin was effective in managing autonomic dysreflexia without causing impairment in erectile function, although some patients reported fatigue, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of terazosin for the treatment of autonomic dysreflexia. Chancellor, MB., Erhard, MJ., Hirsch, IH., et al.[2019]

Terazosin is an effective once-daily medication for lowering blood pressure in patients with mild to moderate hypertension, as demonstrated in four out of five randomized controlled trials.

The drug was well tolerated overall, but some patients experienced side effects like dizziness and peripheral edema, which were more common than in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Terazosin: a new alpha 1-blocker for the treatment of hypertension: a review of randomized, controlled clinical trials of once-daily administration as monotherapy. Luther, RR., Glassman, HN., Sperzel, WD., et al.[2013]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8862665/

A Pilot to Assess Target Engagement of Terazosin ...

Preclinical and epidemiologic data suggest that TZ may be neuroprotective in PD. We aimed to assess target engagement and safety of TZ in people with PD.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05109364

Terazosin and Parkinson's Disease Extension Study

The purpose of this study is to investigate the long-term effects of treatment with the selective post-synaptic a1-adrenergic blocker terazosin on serial in ...

3.

withpower.com

withpower.com/trial/phase-3-parkinson-disease-10-2020-7743d

Terazosin for Early Parkinson's Disease

In a pilot study involving 15 patients with benign prostatic hyperplasia (BPH), terazosin significantly improved both peak and mean urine flow rates, as well as ...

4.

michaeljfox.org

michaeljfox.org/grant/assessing-target-engagement-terazosin

Assessing Target Engagement for Terazosin

We found that the models treated with terazosin had better motor scores and more ATP in their brains. As a result, we looked at databases of humans and found ...

5.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/11/NCT03905811/ICF_002.pdf

A Pilot Study of Terazosin for Parkinson's Disease

data shows that some of its effects could slow down the progression of Parkinson's Disease symptoms. ... No data will be reviewed clinically, and results are not ...

6.

isrctn.com

isrctn.com/ISRCTN17799294

A trial of treatments to slow progression of Parkinson's ...

The trial treatments, telmisartan and terazosin, are repurposed drugs and therefore have a well-known safety profile. The most common side effect expected ...

7.

medrxiv.org

medrxiv.org/content/10.1101/2024.05.22.24307622v1.full-text

A pilot dose-finding study of Terazosin in humans

Conclusions TZ at a dosage of 5 mg/day engages its metabolic targets effectively in both sexes without inducing significant adverse effects and ...