Carbidopa + Levodopa for Parkinsonism

(RES Trial)

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

5 Participants Needed

Trial Summary

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.

What data supports the idea that Carbidopa + Levodopa for Parkinsonism is an effective drug?

The available research shows that Carbidopa + Levodopa, often known as Sinemet, is effective in treating Parkinsonism. One study found that switching from Levodopa alone to the combination with Carbidopa resulted in an average improvement of 51.9% in patients within two weeks. This combination also allowed for a significant reduction in the required dosage of Levodopa by 77%, while reducing side effects like nausea and vomiting. Another study highlighted that Sinemet improved the quality of life and reduced mortality by half, especially in the first three years of treatment. Additionally, Sinemet was found to be as effective as Levodopa alone but required lower doses and had fewer side effects. Overall, these studies suggest that Carbidopa + Levodopa is a superior option for managing symptoms like rigidity and slow movement in Parkinsonism compared to Levodopa alone. ^{1 2 3 4 5}

What safety data is available for Carbidopa and Levodopa treatment in Parkinson's disease?

The safety data for Carbidopa and Levodopa treatment, specifically the long-acting combination CR-4-Sinemet, indicates that side effects are similar to those of traditional Sinemet. In a study with 20 patients experiencing 'wearing-off' phenomena, CR-4-Sinemet showed improved disability and increased 'on' time without additional side effects compared to traditional Sinemet. ^{6 7 8 9 10}

Is the drug Carbidopa-Levodopa a promising treatment for Parkinson's disease?

Yes, Carbidopa-Levodopa is a promising treatment for Parkinson's disease. It improves symptoms like stiffness and slow movement, enhances quality of life, and reduces the need for higher doses of medication. It also causes fewer side effects compared to using Levodopa alone. ^{2 3 4 11 12}

What is the purpose of this trial?

Walking with age becomes both slower and less 'automated', requiring more attention and brain resources. As a result, older adults have a greater risk of negative outcomes and falls. There is an urgent need to identify factors that can help compensate for these harmful factors and reduce walking impairments, as there are currently no effective treatments available. Investigators have recently discovered that \~20% of older adults maintain fast walking speed even in the presence of small blood vessel brain changes and leg problems, thus appearing to be protected against these harmful factors. The investigators work suggests that the brain dopamine (DA) system may be a source of this protective capacity. Investigators have also shown that lower levels of dopamine are associated with slow walking. Investigators will be investigating the role of dopamine on slow walking and other parkinsonian signs in this open-label study using detailed clinical assessment, assessment of dopamine activity, and clinical interventions.

Research Team

Chatkaew Pongmala, PhD

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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 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]

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]

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 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]

References

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

Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. [2013]

2. England 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. [2019]

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

Sinemet and the treatment of Parkinsonism. [2019]

4. Poland pubmed.ncbi.nlm.nih.gov

[Comparison between results achieved by administering L-dopa and Sinemet in parkinsonism in the light of our records]. [2019]

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

Pharmacokinetic comparison of Sinemet and Atamet (generic carbidopa/levodopa): a single-dose study. [2013]

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

Parkinson's disease and motor fluctuations: long-acting carbidopa/levodopa (CR-4-Sinemet). [2019]

7. England pubmed.ncbi.nlm.nih.gov

Adding aprepitant to palonosetron does not decrease carboplatin-induced nausea and vomiting in patients with gynecologic cancer. [2021]

8. Germany 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. [2021]

9. Ireland 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. [2018]

10. England 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. [2020]

11. Australia pubmed.ncbi.nlm.nih.gov

Comparison of enteric-coated levodopa with levodopa-carbidopa combination. A double-blind crossover trial. [2013]

12. Poland pubmed.ncbi.nlm.nih.gov

[Clinical trial of the first Polish levodopa preparation in the treatment of Parkinsonian patients]. [2015]