Interleaving Stimulation Improves Dyskinesia in Parkinson's Disease

NCT ID: NCT06239454

Last Updated: 2024-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-01

Study Completion Date

2025-02-28

Brief Summary

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This study is designed as a prospective, randomized, double-blind, controlled study to assess putative differences in the effect of interleaving stimulation and empirical stimulation with regards to post-operation dyskinesia control. The primary objective is to assess putative differences in the effect of interleaving stimulation and empirical stimulation with regards to dyskinesia control.

Detailed Description

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This study is designed as a prospective, randomized, double-blind, controlled study to assess putative differences in the effect of interleaving stimulation and empirical stimulation with regards to post-operation dyskinesia control. The primary objective is to assess putative differences in the effect of interleaving stimulation and empirical stimulation with regards to dyskinesia control.

50 Patients will be randomly assigned to either the interleaving stimulation modes group (ISG) or the empirical stimulation modes group (ESG). In ISG, empirical stimulation for the first 3 months, followed by interleaving programming period for 6 months, and any stimulation decided by the neurologists/neurosurgeons for the final 3 months. In ESG, empirical programming for the first 9 months' period, followed by any stimulation decided by the neurologists/neurosurgeons for the final 3 months. The change of dyskinesia scores (UPDRS IV, item 32 + item 33), Parkinson's disease quality of life-39 (PDQ-39) scores, scores of United Parkinson's Disease Rating Scale Part III as well as scores of neuropsychological Battery in interleaving stimulation compared to empirical programming modes will be measured based on corresponding time frame. Finally, the results will be analyzed via proper statistical methods and thus the conclusion will be drawn.

Conditions

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Parkinson's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

50 Patients will be randomly assigned to either the interleaving stimulation modes group (ISG) or the empirical stimulation modes group (ESG).

ISG: empirical stimulation for the first 3 months, followed by interleaving programming period for 6 months, and any stimulation decided by the neurologists/neurosurgeons for the final 3 months.

ESG: empirical programming for the first 9 months' period, followed by any stimulation decided by the neurologists/neurosurgeons for the final 3 months.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
Randomization is done by computer-generated pairwise according to order of enrolment, so that similar numbers of patients are recruited to each study group. The chief investigator generates the randomization sequence. The randomization scheme is kept in sealed envelopes. The randomization sequence was revealed only to the unmasked clinician responsible for the stimulation programming, but not to the rater. Patients were masked to randomisation group.

Study Groups

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empirical stimulation modes group (ESG)

empirical programming for the first 9 months' period, followed by any stimulation decided by the neurologists/neurosurgeons for the final 3 months.

Group Type ACTIVE_COMPARATOR

empirical stimulation

Intervention Type DEVICE

Patients are settled with simple polar stimulation with combined parameters adjustment (monopolar mode, 60\~90µs pulse width, 130\~185Hz frequency and varied voltage) during the follow-up.

interleaving stimulation modes group (ISG)

empirical stimulation for the first 3 months, followed by interleaving programming period for 6 months, and any stimulation decided by the neurologists/neurosurgeons for the final 3 months.

Group Type EXPERIMENTAL

interleaving stimulation

Intervention Type DEVICE

ILS consists of two rapid and alternate stimulation programs with different contacts, amplitudes, and pulse width but the same frequency up to a maximum of 125Hz. Contact selection is determined by postoperative stereotactic computed tomography and clinical evaluation to achieve a balance between motor improvement and tolerable side effects. For example, ILS is successfully applied for PD motor symptoms (stimulation of subthalamic nucleus) as well as dyskinesia (additional stimulation of zona incerta).

Interventions

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interleaving stimulation

ILS consists of two rapid and alternate stimulation programs with different contacts, amplitudes, and pulse width but the same frequency up to a maximum of 125Hz. Contact selection is determined by postoperative stereotactic computed tomography and clinical evaluation to achieve a balance between motor improvement and tolerable side effects. For example, ILS is successfully applied for PD motor symptoms (stimulation of subthalamic nucleus) as well as dyskinesia (additional stimulation of zona incerta).

Intervention Type DEVICE

empirical stimulation

Patients are settled with simple polar stimulation with combined parameters adjustment (monopolar mode, 60\~90µs pulse width, 130\~185Hz frequency and varied voltage) during the follow-up.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 1\. Patients at the age of 30-65 years old. 2. Patients diagnosed as Parkinson's disease according to the UK Parkinson's Disease Society Brain Bank criteria.

3\. Patients at Hoehn and Yahr stage 3 or lower in the on-state and stage 2 - 4 in the off-state.

4\. The disease duration of 5 years or more. 5. Patients with deep levodopa-responsive Parkinson's disease, and are not adequately controlled by drug therapy.

Exclusion Criteria

* major illness or medical comorbidities, depression that is untreated but judged to be clinically significant by an investigator, cochlear implants, cardiac pacemakers, needs for diathermy, anticoagulant therapy, previous neuro-surgical procedure or ablative therapy, frank dementia according to cognitive screening, drug or alcohol abuse, being a woman of child-bearing potential, having a positive pregnancy test, or presence of a terminal illness.
Minimum Eligible Age

30 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medtronic

INDUSTRY

Sponsor Role collaborator

Huashan Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jian Wang

Professor of neuroloy department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Feng-Tao Liu, MD

Role: STUDY_DIRECTOR

Huashan Hospital

Locations

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Huashan Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jian-Jun Wu, MD

Role: CONTACT

86-21-52888163

Feng-Tao Liu, MD

Role: CONTACT

86-21-52888163

Facility Contacts

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Jian Wang

Role: primary

86-2152888160

References

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Reference Type BACKGROUND
PMID: 10715510 (View on PubMed)

Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Halbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltete D, Damier P, Raoul S, Sixel-Doering F, Hellwig D, Gharabaghi A, Kruger R, Pinsker MO, Amtage F, Regis JM, Witjas T, Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, Schade-Brittinger C, Deuschl G; EARLYSTIM Study Group. Neurostimulation for Parkinson's disease with early motor complications. N Engl J Med. 2013 Feb 14;368(7):610-22. doi: 10.1056/NEJMoa1205158.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 23168021 (View on PubMed)

Koeglsperger T, Palleis C, Hell F, Mehrkens JH, Botzel K. Deep Brain Stimulation Programming for Movement Disorders: Current Concepts and Evidence-Based Strategies. Front Neurol. 2019 May 21;10:410. doi: 10.3389/fneur.2019.00410. eCollection 2019.

Reference Type BACKGROUND
PMID: 31231293 (View on PubMed)

Kern DS, Picillo M, Thompson JA, Sammartino F, di Biase L, Munhoz RP, Fasano A. Interleaving Stimulation in Parkinson's Disease, Tremor, and Dystonia. Stereotact Funct Neurosurg. 2018;96(6):379-391. doi: 10.1159/000494983. Epub 2019 Jan 17.

Reference Type BACKGROUND
PMID: 30654368 (View on PubMed)

Zhang S, Zhou P, Jiang S, Wang W, Li P. Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease: A report of 12 cases. Medicine (Baltimore). 2016 Dec;95(49):e5575. doi: 10.1097/MD.0000000000005575.

Reference Type BACKGROUND
PMID: 27930569 (View on PubMed)

Franca C, Barbosa ER, Iglesio R, Teixeira MJ, Cury RG. Interleaving Stimulation in Parkinson Disease: Interesting to Whom? World Neurosurg. 2019 Oct;130:e786-e793. doi: 10.1016/j.wneu.2019.06.223. Epub 2019 Jul 8.

Reference Type BACKGROUND
PMID: 31295615 (View on PubMed)

Khabarova EA, Denisova NP, Dmitriev AB, Slavin KV, Verhagen Metman L. Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson Disease with Prior Pallidotomy or Thalamotomy. Brain Sci. 2018 Apr 16;8(4):66. doi: 10.3390/brainsci8040066.

Reference Type BACKGROUND
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Bouthour W, Bereau M, Kibleur A, Zacharia A, Tomkova Chaoui E, Fleury V, Benis D, Momjian S, Bally J, Luscher C, Krack P, Burkhard PR. Dyskinesia-inducing lead contacts optimize outcome of subthalamic stimulation in Parkinson's disease. Mov Disord. 2019 Nov;34(11):1728-1734. doi: 10.1002/mds.27853. Epub 2019 Sep 30.

Reference Type BACKGROUND
PMID: 31571277 (View on PubMed)

Picillo M, Lozano AM, Kou N, Puppi Munhoz R, Fasano A. Programming Deep Brain Stimulation for Parkinson's Disease: The Toronto Western Hospital Algorithms. Brain Stimul. 2016 May-Jun;9(3):425-437. doi: 10.1016/j.brs.2016.02.004. Epub 2016 Feb 12.

Reference Type BACKGROUND
PMID: 26968806 (View on PubMed)

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Reference Type BACKGROUND
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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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https://link.springer.com/book/10.1007/978-1-4613-8643-8

Devroye, Luc. 1986. Non-Uniform Random Variate Generation. Springer-Verlag. New York.

Other Identifiers

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KY2022-507

Identifier Type: -

Identifier Source: org_study_id

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