Alternating-Frequency DBS for Parkinson's Disease

(ENGAGE-PD Trial)

Overseen By James Liao, MD PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: The Cleveland Clinic

Disqualifiers: Orthopedic, Rheumatologic, Neurological, Dementia, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Alternating-Frequency DBS for Parkinson's Disease?

Research suggests that varying the frequency of deep brain stimulation (DBS) can help manage different motor symptoms in Parkinson's disease. For example, combining high and low frequencies in DBS has shown potential to address a wider range of symptoms, such as tremors and movement difficulties. ^{1 2 3 4 5}

What is the safety profile of Deep Brain Stimulation (DBS) for Parkinson's Disease?

Deep Brain Stimulation (DBS) for Parkinson's Disease has some risks, including infections (2-16.2%), bleeding in the brain (1-12.5%), and seizures (1-3%). Some patients may need additional surgery to fix or remove the device due to complications. ^{6 7 8 9 10}

How is Alternating-Frequency DBS different from other treatments for Parkinson's Disease?

Alternating-Frequency DBS is unique because it combines both high and low frequencies in its stimulation pattern, which may help manage a broader range of Parkinson's symptoms, including both motor and axial symptoms like speech and gait issues, compared to traditional fixed-frequency DBS. ^{1 2 3 4 11}

Research Team

James Liao, MD PhD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Alternating-Frequency DBS (Behavioural Intervention)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

Temporally non-regular patterns of deep brain stimulation (DBS) were found to be as effective as traditional fixed-frequency stimulation in managing motor symptoms like tremor and bradykinesia in Parkinson's disease patients.

Using stimulation gaps of 50 ms not only maintained effective symptom control but also allowed for longer recordings of local evoked potentials, suggesting a potential for more efficient and responsive DBS systems in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporally non-regular patterns of deep brain stimulation (DBS) enhance assessment of evoked potentials while maintaining motor symptom management in Parkinson's disease (PD). Palopoli-Trojani, K., Schmidt, SL., Baringer, KD., et al.[2023]

In a pilot study involving 4 Parkinson's disease patients, variable frequency stimulation (VFS) showed a 14% greater improvement in motor symptoms compared to high frequency stimulation (HFS).

VFS also significantly enhanced gait speed by 45% and reduced freezing episodes by 58%, indicating its potential effectiveness in managing axial symptoms like freezing of gait.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation at Variable Frequency to Improve Motor Outcomes in Parkinson's Disease. Jia, F., Wagle Shukla, A., Hu, W., et al.[2022]

The study involving 53 patients with Parkinson's disease showed that a new multiple-source, constant-current deep brain stimulation (DBS) system significantly improved motor symptoms, with a mean reduction of 23.8 points in the UPDRS III score after 6 months.

The safety profile of the DBS system was acceptable, with only 18 serious adverse events reported, all of which resolved without lasting effects, indicating that the device is a promising option for managing Parkinson's motor symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study. Timmermann, L., Jain, R., Chen, L., et al.[2022]

In a study involving a single hemi-parkinsonian monkey, varying the stimulation pattern and frequency of deep brain stimulation (DBS) showed that an 80 Hz burst pattern significantly improved movement performance compared to fixed-frequency stimulation, while using 40% less energy.

The findings suggest that lower frequency bursting patterns can be as effective as higher frequency continuous stimulation for treating bradykinesia, which could lead to longer battery life for DBS devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pallidal stimulation: effect of pattern and rate on bradykinesia in the non-human primate model of Parkinson's disease. Baker, KB., Zhang, J., Vitek, JL.[2021]

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is more effective at reducing tremors in Parkinson's disease patients when they are off medication, while low-frequency stimulation (LFS) is better for improving akinesia, gait, and freezing of gait.

The study analyzed data from 10 studies involving 132 patients and found that while HFS and LFS did not significantly differ in overall motor symptom scores, they had distinct benefits for specific symptoms, suggesting tailored stimulation settings could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson's disease: a meta-analysis of controlled trials. Su, D., Chen, H., Hu, W., et al.[2019]

In a study of 124 patients with Parkinson's disease who underwent deep brain stimulation, 17.7% experienced complications related to implanted devices, including infections and ulcers.

Surgical revision for culture-negative ulcers showed a significantly higher healing rate (80%) compared to culture-positive ulcers (16.6%), indicating that the type of ulcer may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complications related with implanted devices in patients with Parkinson's disease treated with deep brain stimulation. A study of a series of 124 patients over a period of 16 years]. de Quintana-Schmidt, C., Pascual-Sedano, B., Alvarez-Holzapfel, MJ., et al.[2014]

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease, allowing patients to reduce their reliance on anti-Parkinson medications and save an average of $2,292 per year after surgery, based on a study of 72 patients.

While DBS is generally safe, the most common adverse event was intracranial hemorrhage occurring in 12.5% of patients, with a small percentage experiencing permanent or transient deficits, indicating that while effective, there are risks associated with the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for Parkinson's disease: the Vanderbilt University Medical Center experience, 1998-2004. Gill, CE., Konrad, PE., Davis, TL., et al.[2007]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improved motor symptoms in a 44-year-old woman with Parkinson's disease, but also caused uncontrollable laughter, highlighting the potential for neurobehavioral side effects.

The use of directional electrodes allowed for more precise stimulation, which helped to minimize undesirable side effects while optimizing motor improvement, suggesting that careful programming and electrode placement are crucial for effective DBS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-motor Adverse Effects Avoided by Directional Stimulation in Parkinson's Disease: A Case Report. Alonso-Frech, F., Fernandez-Garcia, C., Gómez-Mayordomo, V., et al.[2022]

Variable-frequency stimulation (VFS) using a combination of high frequencies improved both tremor and speech problems in a patient with advanced Parkinson's disease, suggesting a potential new approach to treatment.

This case highlights that while traditional high-frequency deep brain stimulation (STN-DBS) can alleviate primary motor symptoms, it may not address axial symptoms; VFS could offer a more effective solution, warranting further research in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variable High-Frequency Deep Brain Stimulation of the Subthalamic Nucleus for Speech Disorders in Parkinson's Disease: A Case Report. Zhang, C., Pan, Y., Zhou, H., et al.[2020]

References

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

Temporally non-regular patterns of deep brain stimulation (DBS) enhance assessment of evoked potentials while maintaining motor symptom management in Parkinson's disease (PD). [2023]

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

Deep Brain Stimulation at Variable Frequency to Improve Motor Outcomes in Parkinson's Disease. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study. [2022]

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

Pallidal stimulation: effect of pattern and rate on bradykinesia in the non-human primate model of Parkinson's disease. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson's disease: a meta-analysis of controlled trials. [2019]

6. Spain pubmed.ncbi.nlm.nih.gov

[Complications related with implanted devices in patients with Parkinson's disease treated with deep brain stimulation. A study of a series of 124 patients over a period of 16 years]. [2014]

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

Deep brain stimulation for Parkinson's disease: the Vanderbilt University Medical Center experience, 1998-2004. [2007]

8. Spain pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. [2013]

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

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. [2023]

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

Non-motor Adverse Effects Avoided by Directional Stimulation in Parkinson's Disease: A Case Report. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Variable High-Frequency Deep Brain Stimulation of the Subthalamic Nucleus for Speech Disorders in Parkinson's Disease: A Case Report. [2020]