Alternating-Frequency DBS for Parkinson's Disease

(ENGAGE-PD Trial)

Overseen By James Liao, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The Cleveland Clinic

Disqualifiers: Orthopedic, Rheumatologic, Neurological, Dementia, 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: Unknown

Duration: Duration not specified

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using Deep Brain Stimulation (DBS) to help individuals with Parkinson’s Disease improve balance and walking. The researchers focus on alternating frequencies in DBS to determine if it can better address these and other movement-related symptoms. Individuals with Parkinson’s who already use a specific type of DBS device and experience balance or walking issues might be suitable candidates. Participants should be able to walk unaided when not taking medications. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that Alternating-Frequency DBS is safe for Parkinson's Disease?

Research has shown that Deep Brain Stimulation (DBS) effectively treats Parkinson's disease, alleviating symptoms such as tremors, stiffness, and slow movement. The FDA has approved DBS for Parkinson's, indicating its general safety for this condition.

While researchers continue to study the safety of Alternating-Frequency DBS, evidence suggests that DBS, including various frequency methods, is usually well-tolerated. Many patients experience significant improvement in movement symptoms without serious side effects. However, as with any medical treatment, risks exist, and some individuals may experience side effects like headaches or dizziness.

This study is in its early stages, primarily focusing on understanding safety and side effects. Researchers closely monitor participants' health to manage any potential risks. Although this specific frequency method is new, the established safety of DBS provides a reassuring background for its use in treating Parkinson's. ^{1 2 3 4 5}

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

Alternating-Frequency DBS is unique because it offers a new approach to managing Parkinson's disease by varying the frequency of deep brain stimulation (DBS). Unlike traditional DBS, which uses a constant frequency to manage symptoms, this technique aims to optimize brain stimulation by alternating frequencies, potentially leading to better control of motor symptoms and fewer side effects. Researchers are excited about this treatment because it could provide more personalized and effective symptom management for patients with Parkinson's disease, potentially improving their quality of life compared to current therapies.

What evidence suggests that Alternating-Frequency DBS is effective for Parkinson's Disease?

Research has shown that Deep Brain Stimulation (DBS) can greatly improve movement problems such as shaking, slow movement, and stiffness in people with Parkinson's Disease (PD). Some studies suggest that using DBS at higher settings, above 100 Hz, might enhance these movement benefits. However, DBS does not significantly improve balance problems in PD patients. Overall, DBS has reduced both movement and non-movement symptoms by 60-80%, allowing many patients to reduce their medication. In this trial, all participants will receive Alternating-Frequency DBS, which researchers are investigating to determine if different DBS settings can provide even better results. ^{2 5 6 7 8}

Who Is on the Research Team?

James Liao, MD PhD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

I can walk without help and without taking any medications.

Exclusion Criteria

I do not have conditions that severely affect my walking or balance.

I am younger than 21 years old.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants perform a gait task using a new, alternating DBS frequency paradigm while body movements and neural signals are recorded

Duration not specified

Multiple visits for intervention and recordings

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alternating-Frequency DBS

Trial Overview 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.

How Is the Trial Designed?

Group I: Alternating-Frequency DBS Experimental Treatment 8 Interventions

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

Alternating-Frequency DBS is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Obsessive-compulsive disorder
• Tourette syndrome
• Treatment-resistant depression

Approved in United States as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy

Approved in Canada as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Approved in Japan as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

James Liao

Lead Sponsor

Trials

1

Recruited

10+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6207106/

Deep Brain Stimulation at Variable Frequency to Improve ... Several studies have observed that DBS therapy delivered at frequencies higher than 100 Hz improves the motor symptoms in PD, including rigidity, bradykinesia, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1878875024005837

Effectiveness of Deep Brain Stimulation in Improving ... Current research suggests that DBS results in no significant improvement in balance dysfunction for people with PD.

3. nature.com nature.com/articles/s41467-024-48731-1

Deep brain stimulation of symptom-specific networks in ... Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10634582/

Advances in Deep Brain Stimulation: From Mechanisms to ... ... Deep brain stimulation at variable frequency to improve motor outcomes in Parkinson's disease. ... DBS frequency effects on freezing of ...

5. tandfonline.com tandfonline.com/doi/full/10.2147/JPRLS.S306244

Full article: Deep Brain Stimulation in Parkinson's Disease DBS has the potential to reduce motor and non-motor PD symptoms by 60–80%, with sustained reduction in medication use by 44% after 8 to 15 years ...

6. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/study-suggests-feasibility-of-alternating-frequency-dbs-for-gait-impairment-in-parkinsons

Study Suggests Feasibility of Alternating-Frequency DBS for ... A new study is testing whether using an alternating-frequency protocol for deep brain stimulation may improve gait in Parkinson's disease ...

7. jneurosci.org jneurosci.org/content/43/45/7575

Advances in Deep Brain Stimulation: From Mechanisms to ... The FDA has approved DBS in the treatment of Parkinson's disease (PD), essential tremor (ET), and epilepsy, and granted Humanitarian Device ...

8. neurologyadvisor.com neurologyadvisor.com/features/deep-brain-stimulation-parkinson-disease/

Deep Brain Stimulation in Parkinson Disease Treatment Clinical outcomes with DBS have been consistently favorable across PD symptoms. “Modern DBS treatment typically achieves a 50% or greater ...