Carvedilol for Early Parkinson's Disease

Recruiting at 1 trial location

Overseen By MaryClare Kelly, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Michele Tagliati, MD

Must not be taking: Antidepressants

Disqualifiers: Dementia, Heart failure, Diabetes, COPD, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 26 weeks

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking medications for conditions like heart failure, hypertension, or depression, you may need to discuss this with the trial team, as these conditions are part of the exclusion criteria.

Is carvedilol safe for use in humans?

Carvedilol, also known by names like Coreg and Dilatrend, is generally considered safe for human use as it has been used for other conditions like heart disease. It has antioxidant and anti-inflammatory properties, and studies in rats suggest it may protect brain cells, but more research is needed to confirm its safety specifically for Parkinson's Disease. ^{1 2 3 4 5}

How is the drug Carvedilol different from other treatments for Parkinson's disease?

Carvedilol is unique because it is a beta-blocker, which is typically used to manage heart conditions, but it may help control tremors in Parkinson's disease. Unlike traditional Parkinson's treatments like L-dopa, which primarily address movement symptoms, beta-blockers like Carvedilol target tremors specifically. ^{6 7 8 9 10}

What is the purpose of this trial?

REM Behavior Sleep Disorder (RBD) is a sleep disorder causing people to 'act out' their dreams. A high percentage of individuals with idiopathic RBD (iRBD) are known to develop conditions affecting the neurons in the brain such as Parkinson's disease (PD). Based on the increased risk to develop PD, individuals with iRBD are currently considered ideal candidates for therapies that can possibly protects brain cells, due to the critical window of opportunity to intervene early before brain cell loss progresses significantly. Early changes of PD are associated with a number of symptoms including loss of smell, constipation, anxiety and depression. In addition, early heart and brain abnormalities can be visualized using specialized imaging techniques called 123I-MIBG myocardial scintigraphy (MIBG) and dopamine transporter (DAT) single photon emission computerized tomography (SPECT) respectively. The combined presence of certain symptoms and the use of these imaging techniques are considered early markers of PD in individuals with iRBD. In other conditions, like heart failure, MIBG abnormalities are reversed by drugs able to block excessive adrenergic stimulation, known as beta-blockers. In this study the investigators want to learn about the effect of treatment with the beta-blocker carvedilol on MIBG abnormalities found in iRBD patients at risk to develop PD. The investigators believe that reversing the MIBG abnormality might prelude to a slowing of the neurodegenerative process. This drug is approved by the U.S. Food and Drug Administration (FDA) for congestive heart failure, hypertension and left ventricular dysfunction after myocardial infarction. However, carvedilol is not approved by the FDA in patients with iRBD at risk for PD. The available doses for this drug oral formulations are 3.125mg, 6.25mg, 12.5mg and 25mg. Changes visualized with the MIBG imaging technique will be correlated to the presence and severity of neurological (i.e. tremors, stiffness, slow movements, walking difficulties) and other symptoms associated with PD (i.e. abnormal smell, constipation, depression, color vision abnormalities), as measured by specific clinical scales and exams.

Research Team

Michele Tagliati, MD, FAAN

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

This trial is for people aged 25-85 with REM Sleep Behavior Disorder or hyposmia, who may be at risk of developing Parkinson's Disease. They should have certain symptoms like loss of smell, constipation, depression, or abnormal heart imaging results but must not have severe heart issues, lung conditions like COPD or asthma, recent strokes or myocardial infarction, dementia, severe depression or other serious health problems.

Inclusion Criteria

You have hyposmia (poor sense of smell), functional constipation, abnormal color vision, symptoms of depression, or abnormal heart test results. You can also understand the study and give informed consent.

I have been diagnosed with REM sleep behavior disorder or have a reduced sense of smell.

I am between 25 and 85 years old.

Exclusion Criteria

I have diabetes.

I have severe liver problems.

I have a heart condition that affects how my heart pumps blood.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive carvedilol therapy, with dosage gradually increased to 50 mg/day over 6 months

26 weeks

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

2 visits (in-person)

Treatment Details

Interventions

• Carvedilol

Trial Overview The study tests whether the beta-blocker carvedilol can reverse heart abnormalities seen in early Parkinson's disease using MIBG imaging. Carvedilol is FDA-approved for heart failure and hypertension but not yet for this specific use in Parkinson's-related disorders.

Participant Groups

Group I: carvedilol therapy Experimental Treatment 1 Intervention

The dosage of carvedilol will be gradually increased from the initial recommended starting dose of 3.125 mg twice/daily, the target dose will be 25mg twice daily (50 mg/day) and participants will take 50 mg/day carvedilol for 6 months.Subjects that cannot tolerate the 50 mg daily dose, will be offered to continue at the 25 mg daily dose.

Carvedilol is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Coreg for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in European Union as Dilatrend for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in Canada as Eucardic for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Approved in Japan as Carloc for:

• Hypertension
• Heart failure
• Left ventricular dysfunction following myocardial infarction

Who Is Running the Clinical Trial?

Michele Tagliati, MD

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

A review of 402 drug-related adverse events linked to movement disorders revealed that calcium-entry blockers (31%) and benzamides (27%) were the most commonly implicated drugs.

The study found that serious adverse events occurred in nearly 80% of cases, predominantly affecting females and individuals aged 11-30 and 60-80 years, highlighting the need for caution when prescribing these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug-induced extrapyramidal disorders]. Horga, JF., Navarro, M., Peiró, V., et al.[2022]

In a long-term study involving 419 participants with early and advanced Parkinson's disease, ropinirole extended release was found to be safe, with no new or unexpected safety concerns over a median exposure of 1275 days.

Most participants (87%) experienced at least one adverse event, with common issues including back pain and hallucinations, but a majority preferred the once-daily dosing regimen over more frequent dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, open-label, safety study of once-daily ropinirole extended/prolonged release in early and advanced Parkinson's disease. Makumi, CW., Asgharian, A., Ellis, J., et al.[2016]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Neuroprotective repositioning and anti-tau effect of carvedilol on rotenone induced neurotoxicity in rats: Insights from an insilico& in vivo anti-Parkinson's disease study. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

[Drug-induced extrapyramidal disorders]. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Long-term, open-label, safety study of once-daily ropinirole extended/prolonged release in early and advanced Parkinson's disease. [2016]

4. Germany pubmed.ncbi.nlm.nih.gov

[Practical experience on improving activities of daily living competence in Parkinson's patients treated with ropinirole. Results of a applied study]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Non-ergot dopamine agonist rotigotine as a promising therapeutic tool in atypical parkinsonism syndromes: a 24 months pilot observational open-label study. [2017]

6. Austria pubmed.ncbi.nlm.nih.gov

Retrospective evaluation of cardio-pulmonary fibrotic side effects in symptomatic patients from a group of 234 Parkinson's disease patients treated with cabergoline. [2018]

7. Poland pubmed.ncbi.nlm.nih.gov

[Effect of Coretal Polfa (Oxprenolol) on parkinsonian tremor and benign essential tremor]. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Peripheral beta-adrenergic blockade treatment of parkinsonian tremor. [2007]

9. England pubmed.ncbi.nlm.nih.gov

Beta-blocker therapy for tremor in Parkinson's disease. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

[Initiation of treatment in Parkinson disease]. [2015]