Interleaving Stimulation Improves Dyskinesia in Parkinson's Disease

NCT06239454 | Unknown DMC

• 1 other identifier: KY2022-507
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

Interleaving stimulation; dyskinesia syndrome in in Parkinson's disease; randomized, double-blind, controlled trial

Outcome Measures

Primary Outcomes (2)

• dyskinesia scores (United Parkinson's Disease Rating Scale Part IV, item 32 + item 33)

  Measure the changes of dyskinesia scores (United Parkinson's Disease Rating Scale Part IV, item 32 + item 33) in interleaving stimulation compared to empirical programming modes. The total scores range from 0 (good health) to 4 (poor health).

  3 months and 9 months

• Parkinson's disease quality of life-39 (PDQ-39) scores

  Measure the changes of Parkinson's disease quality of life-39 (PDQ-39) scores in interleaving stimulation compared to empirical programming modes. The total scores range from 0 (good health) to 156 (poor health).

  3 months and 9 months

Secondary Outcomes (2)

• scores of United Parkinson's Disease Rating Scale Part III

  3 months and 9 months

• Montreal cognitive assessment scores

  3 months and 9 months

Study Arms (2)

empirical stimulation modes group (ESG)

ACTIVE COMPARATOR

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

Device: empirical stimulation

interleaving stimulation modes group (ISG)

EXPERIMENTAL

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.

Device: interleaving stimulation

Interventions

interleaving stimulation 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).

interleaving stimulation modes group (ISG)

empirical stimulation 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.

empirical stimulation modes group (ESG)

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Huashan Hospital: lead
• Medtronic: collaborator

Study Sites (1)

Huashan Hospital

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

Related Publications (11)

• Wiens BL, Iglewicz B. Design and analysis of three treatment equivalence trials. Control Clin Trials. 2000 Apr;21(2):127-37. doi: 10.1016/s0197-2456(99)00052-5.

  PMID: 10715510 BACKGROUND

• 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.

  PMID: 23406026 BACKGROUND

• Odekerken VJ, van Laar T, Staal MJ, Mosch A, Hoffmann CF, Nijssen PC, Beute GN, van Vugt JP, Lenders MW, Contarino MF, Mink MS, Bour LJ, van den Munckhof P, Schmand BA, de Haan RJ, Schuurman PR, de Bie RM. Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial. Lancet Neurol. 2013 Jan;12(1):37-44. doi: 10.1016/S1474-4422(12)70264-8. Epub 2012 Nov 16.

  PMID: 23168021 BACKGROUND

• 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.

  PMID: 31231293 BACKGROUND

• 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.

  PMID: 30654368 BACKGROUND

• 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.

  PMID: 27930569 BACKGROUND

• 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.

  PMID: 31295615 BACKGROUND

• 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.

  PMID: 29659494 BACKGROUND

• 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.

  PMID: 31571277 BACKGROUND

• 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.

  PMID: 26968806 BACKGROUND

• Aquino CC, Duffley G, Hedges DM, Vorwerk J, House PA, Ferraz HB, Rolston JD, Butson CR, Schrock LE. Interleaved deep brain stimulation for dyskinesia management in Parkinson's disease. Mov Disord. 2019 Nov;34(11):1722-1727. doi: 10.1002/mds.27839. Epub 2019 Sep 4.

  PMID: 31483534 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Feng-Tao Liu, MD

  Huashan Hospital

  STUDY DIRECTOR

Central Study Contacts

Jian-Jun Wu, MD

CONTACT

86-21-52888163; jungliw@gmail.com

Feng-Tao Liu, MD

CONTACT

86-21-52888163; liufengtao@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of neuroloy department

Model Details: 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.

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: February 2, 2024
• Study Start: March 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: February 28, 2025
• Last Updated: February 2, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)