What side effects are associated with this type of intervention?

The most common treatments for Parkinson's Disease include dopaminergic therapies such as levodopa, dopamine agonists, and MAO-B inhibitors. Levodopa can cause nausea, dizziness, orthostatic hypotension, confusion, hallucinations, and dyskinesia. Dopamine agonists may lead to similar side effects, including somnolence, impulse control disorders, and peripheral edema. MAO-B inhibitors generally have milder side effects but can include insomnia and gastrointestinal issues. Deep Brain Stimulation (DBS), particularly Alternating-Frequency DBS, is an invasive procedure that can cause infection, hemorrhage, confusion, and seizures, though severe adverse effects are uncommon. Hardware malfunctions and stimulation-related complications are usually reversible by adjusting the stimulation settings.

What prior FDA approvals exist?

Deep Brain Stimulation (DBS) has been FDA-approved for the treatment of Parkinson's Disease, particularly for patients with advanced symptoms not adequately controlled by medication. DBS involves the implantation of electrodes in specific brain regions, such as the subthalamic nucleus or globus pallidus, to modulate neural activity and improve motor symptoms and postural stability. Other FDA-approved treatments include various dopaminergic medications like levodopa, dopamine agonists, and MAO-B inhibitors, which aim to manage motor fluctuations and other symptoms of Parkinson's Disease.

What other types of research exist?

Promising novel alternatives to Alternating-Frequency Deep Brain Stimulation for Parkinson's Disease patients include: 1) Repetitive Transcranial Magnetic Stimulation (rTMS), which is a noninvasive therapy that uses magnetic fields to stimulate specific brain areas. 2) Transcranial Direct Current Stimulation (tDCS), another noninvasive method that uses a weak electric current to modulate brain activity. 3) High-Frequency Spinal Cord Stimulation (SCS), which has shown efficacy in treating chronic pain and may have potential benefits for PD symptoms. These alternatives offer different mechanisms of action and may provide additional options for patients seeking treatment in 2024.

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Behavioural Intervention

Alternating-Frequency DBS for Parkinson's Disease (ENGAGE-PD Trial)

Q: What is the mechanism of action of this treatment?

The most common treatments for Parkinson's Disease (PD) include pharmacologic agents like levodopa, dopamine agonists, and MAO-B inhibitors, as well as non-pharmacologic interventions such as Deep Brain Stimulation (DBS). Levodopa is converted to dopamine in the brain, replenishing the diminished neurotransmitter and improving motor function. Dopamine agonists mimic dopamine's effects by stimulating dopamine receptors, while MAO-B inhibitors prevent the breakdown of dopamine, prolonging its action. DBS involves the implantation of electrodes in specific brain regions to modulate neural activity, thereby improving motor symptoms and postural stability. These treatments are crucial for PD patients as they address the core issue of dopamine deficiency and abnormal neural activity, significantly enhancing quality of life by reducing motor impairments and improving overall functionality.

Phase 1

Recruiting

Led By Hubert Fernandez, MD

Research Sponsored by The Cleveland Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Bilateral STN DBS for PD

Presence of balance and/or walking impairment and/or freezing of gait

Must not have

Age < 21

Cannot tolerate monopolar stimulation at either of the two middle electrode contacts (prerequisite for the recording mode of the DBS) at high frequency (130 Hz) or low frequency (60 Hz)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up during the intervention

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new type of brain stimulation that changes how often electrical signals are sent to the brain. It aims to help Parkinson's Disease patients who have trouble with balance and walking, problems that current treatments can't fix. By adjusting the stimulation pattern, researchers hope to improve these movement issues.

Who is the study for?

This trial is for people with Parkinson's Disease who have a specific type of brain stimulation device implanted and struggle with balance or walking but can still walk without help. They shouldn't need a walker or cane, have other conditions affecting their gait, be under 21, diagnosed with dementia, or object to being filmed during the study.

What is being tested?

The study tests different patterns of Deep Brain Stimulation (DBS) frequencies to see if they can improve walking and stability in Parkinson's patients. It alternates between high-frequency and low-frequency stimulations over various intervals while monitoring motor symptoms on and off Parkinson's medication.

What are the potential side effects?

Potential side effects may include discomfort from the DBS adjustments, headache, dizziness, or worsening of some Parkinson’s symptoms temporarily due to frequency changes. The exact side effects will depend on individual responses to DBS frequency alterations.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have deep brain stimulation devices in both sides of my brain for Parkinson's.

Select...

I have trouble with balance, walking, or I freeze while walking.

Select...

I can walk without help and without taking any medications.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am younger than 21 years old.

Select...

I cannot tolerate certain stimulation settings required for my deep brain stimulation device.

Select...

I cannot undergo physical therapy due to health reasons.

Select...

I can walk without the need for a cane or walker.

Select...

I have been diagnosed with dementia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ during the intervention

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~during the intervention

This trial's timeline: 3 weeks for screening, Varies for treatment, and during the intervention for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Time with Tremor Present

Stride Time Coefficient of Variation

Tremor Amplitude

Secondary study objectives

Freezing Index

Gait Velocity

LFP and EEG connectivity correlation with behavior and kinematics

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Alternating-Frequency DBSExperimental Treatment8 Interventions

In this single-arm study, all participants will receive all interventions in a crossover fashion.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Parkinson's Disease (PD) include pharmacologic agents like levodopa, dopamine agonists, and MAO-B inhibitors, as well as non-pharmacologic interventions such as Deep Brain Stimulation (DBS). Levodopa is converted to dopamine in the brain, replenishing the diminished neurotransmitter and improving motor function. Dopamine agonists mimic dopamine's effects by stimulating dopamine receptors, while MAO-B inhibitors prevent the breakdown of dopamine, prolonging its action. DBS involves the implantation of electrodes in specific brain regions to modulate neural activity, thereby improving motor symptoms and postural stability. These treatments are crucial for PD patients as they address the core issue of dopamine deficiency and abnormal neural activity, significantly enhancing quality of life by reducing motor impairments and improving overall functionality.