Terazosin Therapy for Parkinson's Disease

Overseen By MaryClare Kelly, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Beta-blockers, Phosphodiesterase 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: 6

Duration: 3 years

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of the drug terazosin on individuals with early signs of Parkinson’s disease. Researchers aim to determine if terazosin can slow brain changes associated with Parkinson’s, potentially easing symptoms and slowing disease progression. Various brain scans will measure these changes over time. Suitable candidates for this trial include those already participating in a related study on early signs of Parkinson’s and who can consent to the trial. 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 requires that you stop taking certain medications, such as beta-adrenergic antagonists and phosphodiesterase type 5 inhibitors like Viagra, Cialis, or Levitra. If you are using any investigational drugs, you must stop them at least 30 days before screening.

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

In a previous study, terazosin showed promise for people with Parkinson's disease. Research suggests that terazosin may help protect brain cells. Studies have also examined its safety and tolerability. For example, an initial study aimed to find the right dose and assess tolerability. This study found that terazosin was generally well-tolerated in people without brain-related conditions.

Additionally, some research suggests that men with Parkinson's who took terazosin experienced slower worsening of movement problems. This indicates that terazosin might not only be safe but also helpful in managing symptoms. Since the current trial is in Phase 2, some existing safety data is available, but more information is needed to fully understand its safety in people with Parkinson's disease. ^{1 2 3 4 5}

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

Unlike the standard Parkinson's treatments like levodopa or dopamine agonists, terazosin stands out because it targets the alpha1-adrenergic receptor, a different mechanism of action. Researchers believe this could slow down the disease's progression by protecting neurons and maintaining dopamine levels, potentially reducing the rate at which patients convert to full-blown parkinsonism. This unique approach offers hope for not just managing symptoms, but also altering the disease's course, which is an exciting prospect for both patients and researchers.

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

Studies have shown that terazosin, the investigational treatment in this trial, might help protect the brain in people with Parkinson’s disease (PD). Research has found that men taking terazosin were 12 to 37% less likely to develop PD compared to those taking a similar drug. Early studies also suggest that terazosin can increase brain energy, which is important for brain health. In animal studies, terazosin improved movement skills and boosted energy levels in the brain. These findings suggest terazosin could slow the progression of PD symptoms by enhancing brain cell function. ^{1 2 6 7 8}

Who Is on the Research Team?

Michele Tagliati, MD, FAAN

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for people who were part of a previous Parkinson's study, can consent, and don't have conditions like secondary Parkinsonism, dementia, severe depression, recent heart issues or certain other health problems. It's not for those with low blood pressure, untreated sleep apnea, heart failure or kidney issues.

Inclusion Criteria

I understand the details of the clinical trial and can consent to participate.

Enrolled in the study 'The Effect of alpha1- adrenergic receptor antagonist Therapy on Cardiac and Striatal Transporter Uptake in Pre-Motor and Symptomatic Parkinson's Disease' (STUDY #000540)

Exclusion Criteria

I have no health issues that prevent me from taking terazosin.

Use of investigational drugs within 30 days before screening

I have had a severe heart condition causing very low blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive terazosin therapy and undergo MIBG scan, DAT scan, and NM-MRI. Subjects return for research visits and imaging every six months.

3 years

Every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of motor and non-motor symptoms.

6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term to further assess the effects of terazosin.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Terazosin

Trial Overview The study tests the long-term effects of Terazosin on people at risk for pre-motor Parkinson's disease. Researchers will look at brain imaging changes and compare them to motor and non-motor symptoms as well as cardiac function over time.

How Is the Trial Designed?

Group I: terazosin therapy extension Experimental Treatment 1 Intervention

Primary procedures in this study are MIBG scan, DAT scan, NM-MRI, and terazosin medication. Subjects will return for research visits and imaging every six months for three years. The investigators hypothesize that the rate of decline in DAT scan123I-Ioflupane uptake will be slower in subjects who have received the alpha1- adrenergic receptor antagonist terazosin, resulting in a decreased clinical conversion rate to parkinsonism.

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

In a pilot study involving 14 patients with Parkinson's disease, rimantadine showed potential antiparkinsonian effects, with 71% of participants reporting a subjective improvement in symptoms and a significant 20% improvement in motor function as measured by the Unified Parkinson's Disease Rating Scale.

The treatment was well-tolerated, with mild side effects, primarily nausea, and a notable improvement in rigidity, suggesting that rimantadine could be a promising option for managing Parkinson's symptoms, warranting further investigation in a larger, controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study on the motor effects of rimantadine in Parkinson's disease. Evidente, VG., Adler, CH., Caviness, JN., et al.[2019]

In a study of 29 patients with Tourette syndrome, aripiprazole was found to be safe and reasonably well tolerated, with a discontinuation rate of 20.7% due to adverse effects.

The most common side effects included sedation (30%) and sleep problems (17%), but most adverse effects were not severe, indicating that while some patients may experience issues, the overall tolerability of aripiprazole is favorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability profile of aripiprazole in patients with Tourette syndrome. Cavanna, AE., Selvini, C., Termine, C., et al.[2015]

In a study involving 11 Parkinson's disease patients experiencing severe symptoms, the addition of 1 mg/day of terguride to their stable levodopa treatment significantly reduced dyskinesias and motor fluctuations.

Terguride, which acts as a partial dopamine agonist, also led to a slight but significant improvement in overall Parkinsonian symptoms, suggesting its potential as a beneficial adjunct therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Terguride in the treatment of Parkinson disease: preliminary experience. Giovannini, P., Piccolo, I., Genitrini, S., et al.[2019]

In a study involving 31 patients with torsion dystonia, trihexyphenidyl demonstrated a clinically significant response in 71% of participants, indicating its efficacy in managing this condition.

After an average follow-up of 2.4 years, 68% of patients continued using trihexyphenidyl, with 42% reporting considerable or dramatic benefits, and the 30-mg dose was generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Torsion dystonia: a double-blind, prospective trial of high-dosage trihexyphenidyl. Burke, RE., Fahn, S., Marsden, CD.[2019]

Sarizotan, a 5-HT1A agonist, has shown promise in reducing dyskinesia symptoms in rat models, specifically decreasing repetitive jaw movements induced by haloperidol, with significant effects observed at doses of 1.5 and 9 mg/kg.

The study suggests that the mechanism of action for sarizotan's effectiveness may involve agonism at 5-HT1A receptors, indicating its potential as a treatment for dyskinesia associated with Parkinson's disease and schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of chronic administration of sarizotan, 5-HT1A agonist/D3/D4 ligand, on haloperidol-induced repetitive jaw movements in rat model of tardive dyskinesia. Rosengarten, H., Bartoszyk, GD., Quartermain, D., et al.[2013]

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]

An 18-year-old male with Tourette's disorder experienced an acute dystonic episode after just 3 days of treatment with aripiprazole, despite the medication being effective at a low dose of 10 mg daily.

This case highlights that aripiprazole, a partial dopamine agonist, can still cause acute dystonia, which is unexpected given its generally favorable safety profile and low incidence of extrapyramidal symptoms reported in short-term trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute dystonia with low-dosage aripiprazole in Tourette's disorder. Fountoulakis, KN., Siamouli, M., Kantartzis, S., et al.[2015]

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]

In a 12-week pilot study involving 13 participants with Parkinson's disease, terazosin (TZ) significantly increased ATP levels in both the brain and blood, indicating its potential to enhance energy metabolism.

While TZ showed promise in engaging its target and improving ATP levels, some participants experienced mild dizziness and orthostatic hypotension, leading to three dropouts, highlighting the need for further safety assessments in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot to assess target engagement of terazosin in Parkinson's disease. Schultz, JL., Brinker, AN., Xu, J., et al.[2023]

A large cohort study involving over 52,000 men in Denmark and nearly 95,000 in the US found that those using terazosin, doxazosin, or alfuzosin had a significantly lower risk of developing Parkinson's disease (PD) compared to those using tamsulosin, with hazard ratios indicating a protective effect.

The study also revealed a dose-response relationship, where longer use of terazosin/doxazosin/alfuzosin correlated with a progressively lower risk of PD, suggesting that these medications may have a beneficial effect on delaying or preventing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Glycolysis-Enhancing α-1 Blockers With Risk of Developing Parkinson Disease. Simmering, JE., Welsh, MJ., Liu, L., et al.[2023]

In a study involving eight patients with Parkinson's Disease, terguride significantly improved neurological symptoms, achieving an average of 50.6% improvement on the Webster scale after 21 days at the highest dose of 1.2 mg.

Terguride demonstrated efficacy similar to dopamine agonists in alleviating symptoms like bradykinesia and rigidity, but importantly, it did not produce the typical side effects associated with those medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of a partial dopamine agonist in drug-free parkinsonian patients. Corsini, GU., Bonuccelli, U., Rainer, E., et al.[2019]

Tandospirone citrate, a selective 5-HT1A agonist, was administered to 10 patients with Parkinson's disease and L-DOPA-induced dyskinesia, showing a 50% effectiveness in reducing dyskinesia severity after 12 weeks.

While tandospirone alleviated dyskinesia in some patients, it also caused slight worsening of parkinsonian features in half of the participants, indicating the need for careful monitoring and further research to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patients with Parkinson's disease]. Kannari, K., Kurahashi, K., Tomiyama, M., et al.[2013]

In a pilot study involving 7 patients with Parkinson's disease, naftazone showed potential efficacy by significantly reducing 'ON-time with troublesome dyskinesia' for 5 out of 7 patients, suggesting it may help manage dyskinesia symptoms.

While naftazone was generally well-tolerated, 4 patients experienced adverse events, mostly mild to moderate, indicating the need for careful monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease. Rascol, O., Ferreira, J., Nègre-Pages, L., et al.[2022]

In rodent models of Parkinson's disease, terazosin was found to preserve cognitive function, suggesting it may protect against cognitive symptoms associated with the disease.

In a study of Parkinson's patients, those starting terazosin had a lower risk of being diagnosed with dementia compared to those on tamsulosin, indicating that terazosin's mechanism of enhancing glycolysis may provide additional cognitive benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycolysis-enhancing α1-adrenergic antagonists modify cognitive symptoms related to Parkinson's disease. Weber, MA., Sivakumar, K., Tabakovic, EE., et al.[2023]

ADS-5102, an extended-release formulation of amantadine, allows for once-daily dosing at bedtime, resulting in higher plasma concentrations of the drug during the day when Parkinson's disease symptoms are most prevalent.

In a phase II/III study, ADS-5102 demonstrated a different pharmacokinetic profile compared to immediate-release amantadine, suggesting it may effectively reduce dyskinesia with potentially fewer central nervous system side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of ADS-5102 (Amantadine) Extended Release Capsules Administered Once Daily at Bedtime for the Treatment of Dyskinesia. Hauser, RA., Pahwa, R., Wargin, WA., et al.[2022]

Citations

1. 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.

2. medicine.uiowa.edu medicine.uiowa.edu/news/2021/02/prostate-drug-associated-lower-risk-parkinsons-disease

Prostate drug associated with lower risk of Parkinson's disease “Men taking terazosin were 12 to 37% less likely to develop Parkinson's disease during follow-up than men taking tamsulosin.” Additionally, the ...

3. 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40785306/

A dose-finding study shows terazosin enhanced energy ... Our data show that TZ increases markers of energy metabolism with a biphasic dose-response and suggest that 5 mg/day TZ may provide maximal ...

5. 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 ...

6. medrxiv.org medrxiv.org/content/10.1101/2024.05.22.24307622v1

A pilot dose-finding study of Terazosin in humans This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects.

7. medicineiowa.org medicineiowa.org/spring-2020/prostate-pill-parkinsons-potential

A prostate pill with Parkinson's potential The data was exciting. It showed that men with Parkinson's disease who were taking terazosin had reduced rates of progressive motor disability compared to men ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03905811

A Pilot Study of Terazosin for Parkinson's Disease The primary goal of this study is to assess the safety and tolerability of TZ in patients with PD. This is a pilot study and is not powered to assess efficacy ...