Dopaminergic Medication Adjustment for Parkinson's Disease

Overseen By Mahima Sharma

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stardots AB

Disqualifiers: Movement disorders, Parkinsonism, Visual limitations, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a three-armed open investigational study that aims to differentiate, quantify, and categorize abnormal eye movements and upper limbs movements in patients with Parkinson's disease. The study is using investigational non-invasive devices for that reason including ANLIVA® Hand Movement and ANLIVA® Eye Movement.

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

The trial protocol does not specify whether you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators.

What safety data exists for dopaminergic treatments in Parkinson's disease?

Safety data for dopaminergic treatments, including levodopa and dopamine agonists, indicate that while these medications are effective in managing Parkinson's disease symptoms, they can also cause adverse effects. Levodopa is associated with motor fluctuations and dyskinesias over time. Dopamine agonists, such as bromocriptine and ropinirole, can cause side effects like nausea, hallucinations, and orthostatic hypotension. Ergoline dopamine agonists have a risk of fibrotic reactions, while non-ergoline agonists reduce this risk. Adverse effects necessitated discontinuation in 46% of patients in one study, but earlier use in less advanced cases showed fewer adverse effects. Post-marketing surveillance has identified additional risks like impulse-control disorders and heart valve fibrosis. Overall, while effective, these treatments require careful management of potential side effects. ^{1 2 3 4 5}

Is dopaminergic medication generally safe for humans?

Dopaminergic medications, including levodopa and dopamine agonists, are generally safe for treating Parkinson's disease, but they can cause side effects like nausea, hallucinations, and low blood pressure. Some patients may experience more serious issues like heart valve problems or impulse-control disorders, especially with long-term use. ^{1 2 3 4 5}

Is increasing the dose of dopaminergic drugs a promising treatment for Parkinson's disease?

Yes, increasing the dose of dopaminergic drugs can be promising for treating Parkinson's disease. Dopaminergic drugs, like levodopa and dopamine agonists, help improve motor symptoms and reduce tremors. They are effective in both early and advanced stages of the disease, and can provide continuous relief from symptoms. ^{2 6 7 8 9}

How does the drug used in the clinical trial differ from other Parkinson's disease treatments?

The clinical trial involves increasing the dose of routine dopaminergic medications to 150% of the usual amount, which is unique because it explores the effects of a higher dosage rather than introducing a new drug. This approach may help manage symptoms more effectively in patients who experience reduced response to standard doses over time. ^{2 6 7 8 9}

What data supports the idea that Dopaminergic Medication Adjustment for Parkinson's Disease is an effective drug?

The available research shows that dopaminergic drugs, including levodopa and dopamine agonists, are effective in reducing tremor in Parkinson's disease. Levodopa can improve tremor by 30 to 50%, and similar improvements are seen with dopamine agonists. These drugs are particularly useful for patients with newly diagnosed tremor-predominant Parkinson's disease and those with advanced disease where levodopa alone is less effective. Additionally, dopamine agonists can help reduce the dose of levodopa needed, which is beneficial for patients experiencing decreased response to levodopa. In a study of 1,599 patients treated with dopamine agonists, 61% showed improvement. This suggests that dopaminergic medication adjustment is an effective option for managing Parkinson's disease symptoms. ^{2 3 7 8 10}

What data supports the effectiveness of the drug adjustment for Parkinson's Disease?

Research shows that dopaminergic drugs, including levodopa and dopamine agonists, can improve symptoms like tremor in Parkinson's Disease, with levodopa showing a 30-50% improvement in tremor scores. Additionally, dopamine agonists have been effective in patients with advanced Parkinson's who no longer respond well to levodopa, suggesting that increasing the dose of these medications might enhance their effectiveness. ^{2 3 7 8 10}

Who Is on the Research Team?

Anas Hannoun, MD

Principal Investigator

Dartmouth Hitchcock medical center, Manchester

Are You a Good Fit for This Trial?

This trial is for Parkinson's Disease patients who can safely receive a higher dose of their usual Parkinson's medication in the clinic. Specific eligibility details are not provided, so it's important to contact the study team for more information.

Inclusion Criteria

I have been diagnosed with Essential Tremor.

Able to understand and sign the informed consent form.

I am healthy and do not have IPD or ET.

Exclusion Criteria

I am unable to sign the consent form.

Visual or physical limitations that prevent the subject from performing the baseline eye study requirements

Being involved in the planning and conduct of the clinical investigation (applies to all sponsor management staff, investigational staff and third-party vendors as applicable)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Initial Assessment

Participants undergo initial tests and assessments, including kinetic tremor and dyskinesia tests, without medication, followed by tests after taking medication

1 day

1 visit (in-person)

Longitudinal Monitoring

Participants repeat study visits and procedures every 6 months for longitudinal monitoring

Up to 18 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after initial assessments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 150% of routine home dopaminergic medications dose
• Evaluation of mathematical models

Trial Overview The study tests how increased doses of dopaminergic medications affect eye and hand movements in Parkinson's patients, using non-invasive devices called ANLIVA® Hand Movement and ANLIVA® Eye Movement.

How Is the Trial Designed?

Group I: ON, One visit Experimental Treatment 1 Intervention

Subject visit one time at clinic for tests and assessments. Subject type are Essential Tremor (ET), Healthy Control (HC) or Idiopathic Parkinson's Disease (IPD). The first arm will include the majority of subjects that will be enrolled in a onetime only study procedure performance. Subjects of this arm will carry the diagnosis of IPD, ET, or HC. After the completion of their first research visit and completing study procedures, there will be no future visits or procedures.

Group II: ON, Longitudinal Experimental Treatment 1 Intervention

IPD subjects will be asked to repeat the study visit and procedures every 6 months for longitudinal monitoring.

Group III: OFF/ON Experimental Treatment 2 Interventions

Subject visit one time at clinic for tests and assessments without medication, carry out tests and assessments, then take medication according to the protocol, then carry our tests and assessments. Subject type are Idiopathic Parkinson's Disease.

150% of routine home dopaminergic medications dose is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Levodopa for:

• Parkinson's disease
• Motor fluctuations
• Dyskinesia

Approved in United States as Carbidopa-levodopa for:

• Parkinson's disease
• Motor fluctuations
• Dyskinesia

Approved in Canada as Dopamine agonists for:

• Parkinson's disease
• Motor fluctuations
• Dyskinesia

Approved in Japan as Levodopa for:

• Parkinson's disease
• Motor fluctuations
• Dyskinesia

Who Is Running the Clinical Trial?

Stardots AB

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

Levodopa and dopamine agonists both provide a mean improvement of 30 to 50% in reducing tremor severity in patients with Parkinson's disease, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS).

Dopamine agonists are particularly effective for newly diagnosed patients with tremor-predominant Parkinson's disease and can also benefit advanced patients whose tremor does not respond to levodopa or anticholinergics, highlighting the need for a tailored approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremor and dopamine agonists. Elble, RJ.[2019]

Patients with motor impairments can achieve sufficient improvement for independent functioning with an average of less than six tablets daily of 25/100 carbidopa/L-dopa.

Bromocriptine mesylate, a dopamine agonist, is more effective when used alongside carbidopa and L-dopa, rather than on its own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments in the treatment of Parkinson's disease. Greer, M.[2013]

Dopamine agonists have become important treatments for advanced Parkinson's disease, helping to bypass damaged neurons and directly stimulate dopamine receptors, which can also allow for a reduction in levodopa dosage.

In a study of 278 patients treated with dopamine agonists over an average of one year, 50% showed improvement, but 46% experienced adverse effects leading to discontinuation, suggesting that earlier intervention in less advanced cases may yield better outcomes with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of levodopa failures: the use of dopamine agonists. Lieberman, AN., Gopinathan, G., Neophytides, A., et al.[2013]

Dopaminergic therapy is effective for managing Parkinson's disease, but there is no consensus on the best timing for starting these medications, highlighting the need for personalized treatment plans.

While some additional medications like bromocriptine can help manage fluctuations in response to levodopa, mental side effects are a concern with all antiparkinsonian drugs, especially in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parkinson's disease in the elderly: current management strategies. Aminoff, MJ.[2015]

In a study of 23 patients with advanced Parkinson's disease, switching from bromocriptine to ropinirole at a dose ratio of approximately 2:1 significantly improved motor symptoms, as indicated by a reduction in Unified Parkinson's Disease Rating Scale (UPDRS) scores.

However, higher dose ratios (5:1 and 3:1) led to increased 'off' time in half of the patients and some experienced worsening symptoms, highlighting the importance of careful dose management when switching medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from bromocriptine to ropinirole in patients with advanced Parkinson's disease: open label pilot responses to three different dose-ratios. Giménez-Roldán, S., Esteban, EM., Mateo, D.[2019]

Chronic low-dose levodopa-carbidopa therapy in 92 Japanese patients with Parkinson's disease showed satisfactory benefits in managing motor disabilities and improving quality of life over an average treatment duration of 6.2 years, with a mean daily dose of 186.4 mg.

The therapy resulted in a low incidence of adverse events, with motor fluctuations at 8.7%, dyskinesias at 6.5%, and hallucinations at 14.1%, indicating that low-dose treatment can be effective and safe when combined with small amounts of dopamine agonists and amantadine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study. Kitagawa, M., Tashiro, K.[2019]

Dopamine receptor agonists, including both ergolinic and non-ergolinic types, are effective for treating symptoms of Parkinson's disease and can help reduce motor complications related to levodopa, but they do not demonstrate a disease-modifying effect.

While these medications can improve symptoms, they also carry risks of adverse reactions such as nausea, hallucinations, and impulse-control disorders, which were identified during both pre-marketing trials and post-marketing surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine receptor agonists for the treatment of early or advanced Parkinson's disease. Perez-Lloret, S., Rascol, O.[2021]

Levodopa (LD) is the most effective treatment for Parkinson's disease, but long-term use can lead to motor fluctuations and dyskinesias, raising concerns about its potential neurotoxicity, although this has not been proven in live studies.

Dopamine agonists (DAs) provide similar symptomatic relief for mild-to-moderate Parkinson's disease with a lower risk of motor complications compared to LD, and they may even help slow neurodegeneration, although they share some adverse effects with LD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine agonists in Parkinson's disease. Tintner, R., Jankovic, J.[2019]

Long-term use of levodopa for treating Parkinson's disease can lead to motor complications like dyskinesia, with the severity linked to the total daily dose and frequency of administration.

Dopamine agonists, especially long-acting ones, are effective as first-line treatments and may help reduce the risk of dyskinesia by providing continuous dopaminergic stimulation, although most currently used agonists primarily target D2 receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Jenner, P.[2019]

Levodopa, the primary treatment for Parkinson's disease, has a short half-life of about 1.5 hours, and its effectiveness diminishes over time as the disease progresses, making stable plasma concentrations crucial for motor function.

New formulations and administration methods, such as sustained-release levodopa and enteral infusions, aim to provide continuous dopaminergic stimulation (CDS) to improve motor performance and reduce fluctuations in plasma levels, enhancing treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic optimisation in the treatment of Parkinson's disease : an update. Nyholm, D.[2022]

Citations

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

Tremor and dopamine agonists. [2019]

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

Recent developments in the treatment of Parkinson's disease. [2013]

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

Management of levodopa failures: the use of dopamine agonists. [2013]

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

Parkinson's disease in the elderly: current management strategies. [2015]

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

Switching from bromocriptine to ropinirole in patients with advanced Parkinson's disease: open label pilot responses to three different dose-ratios. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Dopamine receptor agonists for the treatment of early or advanced Parkinson's disease. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Dopamine agonists in Parkinson's disease. [2019]

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

Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. [2019]

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

Pharmacokinetic optimisation in the treatment of Parkinson's disease : an update. [2022]