Neurostimulation for Sleep Problems in Parkinson's Disease

Recruiting at 3 trial locations

Overseen By Dulce Maroni, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Nebraska

Must not be taking: Anticoagulants

Disqualifiers: Seizures, Heart disease, Alcohol abuse, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is aimed at testing the hypothesis that adaptive stimulation of the Subthalamic Nucleus (STN) drives changes in sleep episode maintenance and improves sleep quality. Investigators will directly test the efficacy of an adaptive stimulation protocol. Study subjects are adults with Parkinson's disease who experience inadequate motor symptom relief, and who have been offered implantation of a deep brain stimulator system targeting STN for the treatment of motor symptoms (standard-of-care). Investigators will implant 20 (n = 10 per clinical site) Parkinson's Disease subjects with the Medtronic RC+S System, enabling the implementation of real-time adaptive stimulation during in-home sleep. Prior to surgery, study subjects will complete clinical sleep questionnaires in an outpatient setting and wear an actigraphy watch for 3 weeks to monitor sleep architecture and sleep fragmentation. Three months after subjects have completed their standard-of-care Deep Brain Stimulation surgery and are optimized in terms of Parkinson's medication and clinical DBS stimulation parameters, we will monitor sleep for an additional 3 weeks, using in-home monitoring. During each week of the in-home monitoring period, subjects will undergo, in a randomized and double-blind fashion, one of three nocturnal stimulation algorithms: Adaptive stimulation, Open-Loop stimulation (standard clinical stimulation therapy) and No stimulation (control). During the 3 weeks of in-home sleep monitoring, we will monitor sleep architecture and sleep fragmentation using an actigraphy watch and subjects will complete a sleep questionnaire. At the end of the 3-week period of sleep-time randomized, blinded stimulation delivery, subjects will return to their standard stimulation therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that anti-Parkinson's medications should be at stable doses for 30 days before joining the study.

What data supports the effectiveness of the treatment Deep Brain Stimulation for sleep problems in Parkinson's Disease?

Research shows that Deep Brain Stimulation (DBS) in Parkinson's patients significantly improves overall sleep quality and motor symptoms, although it doesn't change issues like nighttime urination or daytime sleepiness. ^{1 2 3 4 5}

Is deep brain stimulation safe for humans?

Deep brain stimulation (DBS) has been used in humans, particularly for Parkinson's disease, and is generally considered safe, though specific safety outcomes are not detailed in the provided research articles. ^{1 3 5 6 7}

How is the treatment Deep Brain Stimulation (DBS) unique for sleep problems in Parkinson's disease?

Deep Brain Stimulation (DBS) is unique because it involves implanting electrodes in the brain to improve motor function and potentially enhance sleep quality in Parkinson's disease patients, unlike traditional medications that primarily focus on dopamine replacement. ^{1 2 3 5 6}

Research Team

Aviva Abosch, MD, PhD

Principal Investigator

University of Nebraska

Eligibility Criteria

Adults aged 18-80 with Parkinson's disease and motor symptoms for at least 4 years, who are approved for Subthalamic Nucleus (STN) Deep Brain Stimulation surgery. Participants must not have significant cognitive deficits or untreated depression, no history of drug/alcohol abuse, and cannot be pregnant.

Inclusion Criteria

I have been diagnosed with Parkinson's disease and have had motor symptoms for at least 4 years.

My movement symptoms are severe and need surgery despite medication.

My brain MRI does not show any issues that would prevent surgery.

Exclusion Criteria

I have been diagnosed with Obstructive Sleep Apnea.

I have Parkinson's with mild cognitive issues in at least two areas like memory or attention.

I do not have any health conditions that would make surgery too risky.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person), actigraphy monitoring

Pre-Surgery Monitoring

Participants complete clinical sleep questionnaires and wear an actigraphy watch to monitor sleep architecture and fragmentation

3 weeks

Post-Surgery Optimization

Participants undergo standard-of-care Deep Brain Stimulation surgery and optimization of Parkinson's medication and DBS parameters

3 months

Treatment

Participants undergo randomized, double-blind nocturnal stimulation with adaptive, open-loop, and no stimulation conditions

3 weeks

In-home monitoring

Follow-up

Participants are monitored for changes in sleep quality and efficiency using actigraphy and sleep questionnaires

4 weeks

Treatment Details

Interventions

• Deep Brain Stimulation

Trial Overview The trial is testing an adaptive stimulation protocol using the Medtronic RC+S System during sleep to improve sleep quality in Parkinson's patients. It compares three nocturnal stimulations: Adaptive, Open-Loop (standard therapy), and No stimulation over a period of three weeks.

Participant Groups

Group I: Adaptive DBS stimulation Experimental Treatment 1 Intervention

Subjects experience adaptive stimulation during one week of at-home night sleep.

Group II: Open-loop DBS stimulation Active Control 1 Intervention

Subjects experience open-loop stimulation (standard clinical stimulation therapy based on DBS programming for the treatment of motor symptoms) during one week of at-home night sleep.

Group III: No DBS Stimulation Active Control 1 Intervention

DBS stimulation is turned off (control) during one week of at-home night sleep.

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

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

Approved in Canada as Deep Brain Stimulation for:

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

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Findings from Research

In a study of 11 patients with advanced Parkinson's disease, chronic bilateral subthalamic stimulation (STN-DBS) led to significant improvements in subjective sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI).

Polysomnography results indicated that STN-DBS increased the longest period of uninterrupted sleep and decreased sleep fragmentation, suggesting that the therapy enhances overall sleep architecture despite an increase in nocturnal mobility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep symptoms and polysomnographic architecture in advanced Parkinson's disease after chronic bilateral subthalamic stimulation. Iranzo, A., Valldeoriola, F., Santamaría, J., et al.[2022]

The study developed an adaptive Deep Brain Stimulation (DBS) algorithm that can adjust stimulation based on specific sleep stages, particularly targeting the N3 NREM sleep stage, which is crucial for restorative sleep.

Results from two participants showed high accuracy in classifying N3 sleep stages using intracranial electrocorticography, demonstrating the potential of this technology to improve sleep quality in individuals with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Deep Brain Stimulation for sleep stage targeting in Parkinson's disease. Smyth, C., Anjum, MF., Ravi, S., et al.[2023]

In a study of 40 Parkinson's disease patients undergoing subthalamic deep brain stimulation (STN-DBS), 45% reported significant improvement in sleep quality at 6 months, although this improvement was not statistically significant at 12 months.

The most common benefits included better overall sleep quality and maintenance, but some patients experienced new-onset daytime sleepiness, indicating that while STN-DBS can improve sleep, the effects can vary widely among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. Kharkar, S., Ellenbogen, JR., Samuel, M., et al.[2020]

Bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) significantly improved subjective sleep quality in Parkinson's disease patients, as measured by various scales, with notable improvements observed at the 6-month follow-up.

While STN-DBS did not significantly alter objective sleep parameters from polysomnography, it did lead to a reduction in rapid eye movement sleep latency, indicating some changes in sleep patterns, while subjective improvements in sleep quality were linked to reduced medication needs and better motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A quantitative analysis of the effect of bilateral subthalamic nucleus-deep brain stimulation on subjective and objective sleep parameters in Parkinson's disease. Yin, Z., Bai, Y., Guan, B., et al.[2021]

Deep brain stimulation (DBS) of the subthalamic nucleus significantly improves sleep quality and motor function in Parkinson's patients, as measured by the Parkinson's Disease Sleep Scale (PDSS) and the Unified Parkinson's Disease Rating Scale.

While overall sleep quality improved after DBS surgery, issues like nocturia and daytime sleepiness remained unchanged, even with a reduction in Parkinson's medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus. Hjort, N., Østergaard, K., Dupont, E.[2015]

Subthalamic deep brain stimulation (STN DBS) significantly improved sleep quality in Parkinson's Disease patients, as evidenced by better scores on various sleep assessment tools after 8 months of therapy.

The improvements in sleep quality were attributed to the neuromodulatory effects of STN DBS, which occurred independently of motor symptoms, depression levels, and dopamine replacement therapy dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Effect of Subthalamic Deep Brain Stimulation on Sleep Quality of Parkinson's Disease Patients. Oner, OG., Sunter, G., Jafarova, S., et al.[2022]

Asleep deep brain stimulation (DBS) for Parkinson's disease showed a mean motor improvement of 52.3% on the Unified Parkinson's Disease Rating Scale, which is comparable to the 47.0% improvement seen in the awake group, suggesting that asleep DBS is an effective alternative.

The study found no serious complications related to the surgery, with only a subcutaneous hematoma reported, indicating that asleep DBS may be a safe option for patients undergoing this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Randomized Trial of Asleep versus Awake Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease. Engelhardt, J., Caire, F., Damon-Perrière, N., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Sleep symptoms and polysomnographic architecture in advanced Parkinson's disease after chronic bilateral subthalamic stimulation. [2022]

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

Adaptive Deep Brain Stimulation for sleep stage targeting in Parkinson's disease. [2023]

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

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A quantitative analysis of the effect of bilateral subthalamic nucleus-deep brain stimulation on subjective and objective sleep parameters in Parkinson's disease. [2021]

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

Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus. [2015]

6. Turkey pubmed.ncbi.nlm.nih.gov

Assessment of the Effect of Subthalamic Deep Brain Stimulation on Sleep Quality of Parkinson's Disease Patients. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase 2 Randomized Trial of Asleep versus Awake Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease. [2021]