Interleaving Stimulation Improves Dyskinesia in Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Interleaving Stimulation Improves Dyskinesia in Parkinson's Disease: Randomized, Double-blind, Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06239454
• Other study ID #: KY2022-507
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2022
• Est. completion date: February 28, 2025

Study information

• Verified date: January 2024
• Source: Huashan Hospital
• Contact: Jian-Jun Wu, MD
• Phone: 86-21-52888163
• Email: jungliw[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 28, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dyskinesias
• Parkinson Disease
• Parkinson's Disease

Intervention

Device:
• 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).
• 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.

Locations

Country	Name	City	State
China	Huashan Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Huashan Hospital	Medtronic

Country where clinical trial is conducted

China, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	scores of United Parkinson's Disease Rating Scale Part III	Measure the changes of scores of United Parkinson's Disease Rating Scale Part III in interleaving stimulation compared to empirical programming modes. The total scores range from 0 (good health) to 132 (poor health).	3 months and 9 months
Secondary	Montreal cognitive assessment scores	Measure the scores of Montreal cognitive assessment in interleaving stimulation compared to empirical programming modes. The total scores range from 0 (poor cognition) to 30 (good cognition).	3 months and 9 months

External Links

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