Carvedilol for Early Parkinson's Disease

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug carvedilol can slow the progression of Parkinson's disease (PD) in individuals with idiopathic REM Behavior Sleep Disorder (iRBD). iRBD causes people to physically act out their dreams and links to a higher risk of developing PD, a brain disorder affecting movement. Carvedilol, already used for heart conditions, might help by correcting heart abnormalities seen in people with iRBD and potentially slowing brain cell damage. Those with iRBD and symptoms like loss of smell, constipation, or depression might be suitable candidates for this trial. Participants will take carvedilol daily for six months while researchers monitor changes with heart imaging tests. As a Phase 2 trial, this research measures how well carvedilol works in an initial, smaller group, offering participants a chance to contribute to important findings.

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

Research has shown that carvedilol is generally safe. The FDA has approved this drug for treating heart conditions like heart failure and high blood pressure. However, its safety for people with Parkinson's Disease (PD) remains unclear. Most safety information comes from animal studies, not from individuals with PD.

In long-term studies for other conditions, carvedilol has caused side effects such as dizziness, tiredness, and low blood pressure. Carvedilol is not yet approved for people at risk of developing PD with REM behavior sleep disorder, so the safety information might not fully apply to them.

In studies, participants who couldn't tolerate the full dose continued at a lower dose, indicating some flexibility in managing side effects. While carvedilol appears promising, more research is needed to confirm its safety for people with PD. ^{1 2 3 4 5}

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

Carvedilol is unique because it’s being explored for Parkinson's disease, a condition where the current standard of care includes medications like levodopa and dopamine agonists. Unlike these treatments, which primarily aim to replenish or mimic dopamine, carvedilol is a beta-blocker traditionally used for heart conditions. Researchers are excited about carvedilol because it may offer neuroprotective benefits, potentially slowing disease progression by reducing oxidative stress and inflammation in the brain. This novel approach could complement existing therapies by addressing different aspects of Parkinson's beyond just symptom management.

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

Research has shown that carvedilol might protect the brain from damage leading to Parkinson's disease. In animal studies, carvedilol prevented movement and memory problems caused by a toxin similar to that which causes Parkinson's. These findings suggest that carvedilol could slow or stop similar damage in humans. This trial will administer carvedilol therapy to participants to explore its potential benefits for early Parkinson's disease. Carvedilol, already used to treat heart conditions by blocking certain stress signals, might also help people at risk for Parkinson's by reducing early heart and brain changes linked to the disease. Although more research is needed, early findings are promising. ^{6 7 8 9 10}

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 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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299922004654

Insights from an insilico& in vivo anti-Parkinson's disease ... Carvedilol (5 and 10 mg/kg) prevented rotenone-induced motor deficits, spatial memory dysfunction, and histological damage.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12441273/

Approaches for treating cardiovascular symptoms in ... In comparison to delayed OH, classical OH has worse outcomes in motor, non-motor, cognitive, and cortical thickness in PD patients as shown by ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6881195/

β2-adrenoreceptor medications and risk of Parkinson ... A recent study observed a two-fold greater risk of Parkinson disease (PD) in relation to the β2-adrenoreceptor antagonist propranolol and a markedly lower risk ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S156816372200112X

Beta-adrenergic drugs and risk of Parkinson's disease Beta-antagonist use was associated with a modestly increased risk of PD, whereas beta-agonist use was associated with a modest decreased risk of PD.

5. researchgate.net researchgate.net/publication/362648703_Title_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

Title: Neuroprotective repositioning and anti-tau effect of ... Carvedilol (5 and 10 mg/kg) prevented rotenone-induced motor deficits, spatial memory dysfunction, and histologicaldamage. Additionally, carvedilol ...

6. withpower.com withpower.com/trial/phase-3-parkinson-disease-11-2019-f9c08

Carvedilol for Parkinson's Disease · Info for Participants It is generally considered safe, with known side effects ... safety data for its use in Parkinson's Disease is limited to animal studies. ... In a long-term study ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11979683/

Association Between β‐Adrenoreceptor Agonists and ... The quality and quantity of the available evidence do not support a causal association between use of β‐adrenoreceptor modulators and PD.

8. go.drugbank.com go.drugbank.com/drugs/DB01136/clinical_trials?conditions=DBCOND0129382%2CDBCOND0042671%2CDBCOND0116226&phase=2&purpose=treatment&status=enrolling_by_invitation

Carvedilol Enrolling by Invitation Phase 2 Trials for Pre- ... Carvedilol Enrolling by Invitation Phase 2 Trials for Pre-motor Parkinson's Disease / Symptomatic Parkinson Disease / Rapid Eye Movement Sleep Behavior Disorder ...

9. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.108

β2‐adrenoceptor agonists and antagonists and risk of ... Use of propranolol appears to be associated with an increased risk of PD, whereas use of β2-agonists is associated with a decreased risk of PD.

10. clinicalstudydatarequest.com clinicalstudydatarequest.com/Posting.aspx?ID=14388&GroupID=SUMMARIES

Assessing heterogeneity in relative treatment efficacy ... Using ES, results from clinical trials may be combined with other data to estimate treatment effects for particular groups. However, ES has not yet been ...