Carbidopa + Levodopa for Parkinsonism

(RES Trial)

No longer recruiting at 1 trial location

Overseen By Robert Vangel, BSc

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Michigan

Must not be taking: MAOIs, D2 antagonists

Disqualifiers: Dementia, Stroke, Glaucoma, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a combination of medications, Carbidopa and Levodopa (commonly known as Sinemet), might improve walking and other movement issues in older adults with mild Parkinson-like symptoms. Researchers believe that boosting dopamine, a brain chemical, could help maintain faster walking speeds and reduce the risk of falls. The trial is open to those 60 and older who have noticed a slowdown in their walking but have not been diagnosed with Parkinson's disease. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage medical advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot participate if you've been on monoamine oxidase inhibitors (MAOIs) within 2 weeks before starting the study or if you're taking dopamine D2 receptor antagonists, dopamine depleting agents, and metoclopramide.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that most people tolerate carbidopa and levodopa well when used together. This combination commonly treats Parkinson's disease and alleviates symptoms like shaking and stiffness. Studies have found that adding carbidopa reduces nausea that might occur with levodopa alone. Some individuals might experience side effects, such as dizziness or behavioral changes, including strong urges to gamble or spend money. These medications are generally considered safe, as they are approved for treating Parkinson's disease. However, a doctor should monitor patients to manage any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Carbidopa and Levodopa for treating Parkinsonism because it offers a potentially faster onset of symptom relief. Most treatments for Parkinsonism, like standard Levodopa therapy, require careful titration and may take time to adjust to optimal doses. However, this treatment plan starts with Carbidopa alone, which may help minimize initial side effects, before introducing Carbidopa-Levodopa together. By gradually increasing the dose over a short period, this approach aims to enhance the effectiveness while maintaining tolerability, potentially offering improved symptom management in just ten days.

What evidence suggests that Carbidopa and Carbidopa-Levodopa might be effective treatments for slow walking in older adults?

Research shows that combining carbidopa and levodopa effectively treats Parkinson's disease symptoms. Studies have found that this combination improves movement and reduces symptoms like stiffness and shaking. In this trial, participants will receive both Carbidopa monotherapy and Carbidopa-Levodopa combination therapy. Carbidopa reduces side effects like nausea, making the treatment easier for patients to handle. Some research also suggests that this treatment may aid changes in movement control. While primarily used for Parkinson's, the role of dopamine in walking speed suggests that this combination might also benefit older adults who walk slowly. ^{3 6 7 8 9}

Who Is on the Research Team?

Chatkaew Pongmala, PhD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for older adults experiencing slower walking and potential parkinsonian signs. Participants should be interested in exploring how dopamine activity affects their mobility. Key eligibility includes being of a certain age where walking impairments are common, with no specific exclusions provided.

Inclusion Criteria

I am 60 years old or older.

I walk slowly due to mild Parkinson's symptoms.

Exclusion Criteria

I need help to stand or walk.

I have been diagnosed or treated for Parkinson's disease.

Hypersensitivity to the carbidopa, levodopa, and tablet components

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Carbidopa monotherapy and Carbidopa-Levodopa for 10 days to assess the impact on gait speed

10 days

Daily visits for medication administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carbidopa
• Carbidopa-Levodopa

Trial Overview

The study investigates the impact of dopamine on walking speed and parkinsonism by administering Carbidopa and Carbidopa-Levodopa to participants. It's an open-label study, meaning everyone knows which treatment they're getting, focusing on clinical assessments and dopamine activity.

How Is the Trial Designed?

Group I: Carbidopa Monotherapy and Carbidopa-Levodopa Experimental Treatment 2 Interventions

Participants will begin by taking 25mg of Carbidopa monotherapy three times per day (TID) for 3 days. On day four, participants will begin taking 1 tablet of Carbidopa-Levodopa (25/100mg) TID in addition to the Carbidopa monotherapy. On day seven, participants will increase to 1.5 tablets of Carbidopa-Levodopa (25/100mg) TID while maintaining 25mg Carbidopa monotherapy TID. The intervention will end after ten days of supplementation.

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

Approved in United States as Lodosyn for:

• Parkinson's disease
• Dopa-responsive dystonia

Approved in Canada as Atamet for:

• Parkinson's disease
• Dopa-responsive dystonia

Approved in European Union as Carbidopa for:

• Parkinson's disease
• Dopa-responsive dystonia

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 21 patients with Parkinson's disease, the combination of levodopa and carbidopa (Sinemet) led to an average improvement of 51.9% in clinical condition within just 2 weeks, compared to levodopa alone.

Using the combination therapy allowed for a significant reduction in the daily dosage of levodopa by 77%, while also reducing gastrointestinal side effects and avoiding arrhythmogenic effects, indicating a safer and more effective treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative clinical investigation of the therapeutic effect of levodopa alone and in combination with a decarboxylase inhibitor (carbidopa) in cases of Parkinson's disease. Wajsbort, J., Dorner, A., Wajsbort, E.[2019]

In a study of 18 patients with Parkinson's disease, Sinemet (L-dopa and carbidopa) was found to provide the same therapeutic benefits as L-dopa alone but at lower doses and with fewer side effects.

Both Sinemet and L-dopa were most effective in reducing bradykinesia and muscular rigidity, while their impact on tremors was less pronounced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison between results achieved by administering L-dopa and Sinemet in parkinsonism in the light of our records]. Szulc-Kuberska, J., Niewodniczy, A., Poźniak-Patewics, E., et al.[2019]

Intravenous NEPA, a combination of netupitant and palonosetron, was found to be well-tolerated and had a similar safety profile to oral NEPA in a study involving 404 patients undergoing highly emetogenic chemotherapy.

Both intravenous and oral NEPA showed low rates of treatment-related adverse events (12.8% for i.v. NEPA and 11.4% for oral NEPA), with no serious adverse events reported, indicating its safety for preventing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy. Schwartzberg, L., Roeland, E., Andric, Z., et al.[2020]

In a double-blind crossover trial involving 27 patients with idiopathic Parkinson's disease, both enteric-coated levodopa (Prodopa) and levodopa-carbidopa combination (Sinemet) effectively stabilized patients' conditions, demonstrating a dose-sparing effect.

The levodopa-carbidopa combination was found to be more effective in 71% of patients, although there was no strong preference for either treatment among the participants, indicating that both medications are valuable in managing Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of enteric-coated levodopa with levodopa-carbidopa combination. A double-blind crossover trial. Gilligan, B., Wodak, J., Stark, R., et al.[2013]

In a study of 106 gynecologic cancer patients receiving paclitaxel and carboplatin chemotherapy, the addition of aprepitant to palonosetron and dexamethasone did not significantly improve the complete response rate or reduce nausea and vomiting compared to those who did not receive aprepitant.

The complete response rates were similar between the control group (73.1%) and the aprepitant group (74.1%), indicating that aprepitant may not be necessary for managing nausea and vomiting in this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding aprepitant to palonosetron does not decrease carboplatin-induced nausea and vomiting in patients with gynecologic cancer. Watanabe, Y., Saito, Y., Mitamura, T., et al.[2021]

In a multicenter study of lung cancer patients undergoing carboplatin-based chemotherapy, a one-day dexamethasone (DEX) regimen combined with 5-HT3RA and aprepitant (APR) resulted in significantly higher rates of delayed nausea compared to a multiple-day DEX regimen.

The findings suggest that while a DEX-sparing strategy may be considered, it should be approached with caution due to the increased risk of nausea, indicating the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of one-day versus multiple-day dexamethasone for chemotherapy-induced nausea and vomiting in lung cancer patients receiving carboplatin-based chemotherapy: a propensity score-matched analysis. Hayashi, T., Shimokawa, M., Mizuki, F., et al.[2021]

Sinemet, a combination of levodopa and carbidopa, has significantly improved the treatment of parkinsonism by reducing side effects like nausea and arrhythmias, while providing effective relief from rigidity and akinesia, especially in the first three years of treatment.

Despite its benefits, Sinemet can lead to complications such as involuntary movements and psychosis, and it is not a cure for parkinsonism; ongoing research into other drugs and neurotransmitter mechanisms offers hope for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sinemet and the treatment of Parkinsonism. Boshes, B.[2019]

In a 6-week study involving 30 patients with Parkinson's disease, both a foreign levodopa preparation and its Polish analogue showed similar therapeutic effects in reducing symptoms, as measured by the NUDS and NSP scales.

There were no significant differences in the incidence of adverse effects between the two drug preparations, indicating that both are equally safe for use in treating Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical trial of the first Polish levodopa preparation in the treatment of Parkinsonian patients]. Kuran, W., Kulczycki, J.[2015]

Sinemet CR, a controlled-release formulation of carbidopa/levodopa, provides a more stable and extended effect for Parkinson's patients, reducing daily dosing from 10.2 to 5.4 doses while improving clinical outcomes.

Although Sinemet CR has a slower onset of action compared to standard carbidopa/levodopa, it results in less variability in plasma levodopa levels and offers significant benefits in reducing peak-dose and 'wearing-off' effects for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. LeWitt, PA., Nelson, MV., Berchou, RC., et al.[2013]

In a study involving 30 Parkinson's disease patients, there were no significant differences in the pharmacokinetic profiles or motor responses between Sinemet and Atamet, indicating similar effectiveness for both medications.

Both drugs reached peak plasma concentrations within about 49 minutes for Sinemet and 47 minutes for Atamet, and showed comparable effects on motor function, suggesting that Atamet can be a suitable alternative to Sinemet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic comparison of Sinemet and Atamet (generic carbidopa/levodopa): a single-dose study. Pahwa, R., Marjama, J., McGuire, D., et al.[2013]

In a study of 20 Parkinson's disease patients, the long-acting levodopa/carbidopa combination (CR-4-Sinemet) significantly reduced the number of daily doses needed and improved disability and 'on' time compared to traditional Sinemet after 4 to 6 weeks of treatment.

After 3 months of CR-4-Sinemet therapy in 9 patients, the benefits in reduced daily doses and increased 'on' time without chorea were still evident, with similar side effects to traditional Sinemet, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parkinson's disease and motor fluctuations: long-acting carbidopa/levodopa (CR-4-Sinemet). Goetz, CG., Tanner, CM., Klawans, HL., et al.[2019]

In a study of 80 chemotherapy-naïve patients with advanced non-small-cell lung cancer, both triple antiemetic therapy (aprepitant, palonosetron, and dexamethasone) and double therapy (palonosetron and dexamethasone) showed high complete response rates for preventing chemotherapy-induced nausea and vomiting, with rates of 80.5% and 76.9%, respectively.

The addition of aprepitant did not significantly improve the efficacy compared to the double therapy, and both treatment groups had similar incidences of adverse events, suggesting that the triple therapy may not be necessary for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of palonosetron and dexamethasone with or without aprepitant to prevent carboplatin-induced nausea and vomiting in patients with advanced non-small-cell lung cancer. Kusagaya, H., Inui, N., Karayama, M., et al.[2018]

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One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement ...

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Levodopa

Levodopa alone can produce nausea and vomiting, but when combined with carbidopa this side effect is significantly lessened if not eliminated.

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The results of this study suggest that IPX203 vs immediate-release carbidopa-levodopa may be useful in patients with Parkinson disease and motor fluctuations.

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Carbidopa and levodopa (oral route) - Side effects & dosage

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Carbidopa (Lodosyn): Uses, Side Effects, Dosage & More

Carbidopa (Lodosyn) and other Parkinson's disease medications can cause changes in people's behavior, including strong sexual or gambling urges, urges to spend ...