Simultaneous DBS of the GPi and the NBM in Patients With Parkinson's Disease and Mild Cognitive Impairment

NCT ID: NCT05320523

Last Updated: 2022-04-11

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

UNKNOWN

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-20

Study Completion Date

2024-01-31

Brief Summary

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Phase 1 study evaluating the safety of combined bilateral globus pallidus internus (GPi) and nucleus basalis of Meynert (NBM) stimulation in treating levodopa responsive motor symptoms of Parkinsonism and cognitive dysfunction, respectively, in patients with moderate to advanced Parkinson's disease having mild cognitive impairment.

Detailed Description

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This study aims to provide a proof of safety of combined bilateral Globus Pallidus internus (GPi) and Nucleus Basalis of Meynert (NBM) stimulation in patients with moderate to advanced Parkinson's disease having mild cognitive impairment.

GPi stimulation with high-frequency ameliorates the cardinal motor symptoms and motor complications in Parkinson's disease patients, and this present study also wants to determine if additional NBM stimulation, with low-frequency stimulation, improves or slows progression of cognitive decline in patients with moderate to advanced Parkinson's disease having mild cognitive impairment, and to evaluate the effect of NBM stimulation on gait and balance impairment.

Study Design: Prospective single center Phase 1 study with double-blind randomized delayed activation of basal nucleus of Meynert neurostimulation (staggered onset design).

Planned Number of Subjects: 10 patients.

Planned Number of Sites / Countries: Single center in Brazil.

Study schedule:

* Presurgical baseline evaluation (motor on and off medication state; cognitive testing in best motor on state).
* DBS Implant Procedure.
* Postsurgical baseline evaluation (motor off state; cognitive testing in best motor on state) at 3±1 weeks after surgery and activation of globus pallidus internus neurostimulation using individualized stimulation parameters after a standard monopolar review.
* Regular adjustments of the GPi stimulation parameters aiming at the best motor improvement.
* Visit 1 (16 weeks after activation of GPi neurostimulation): motor off medication + GPi stimulation state, cognitive testing in on medication + GPi stimulation state. Randomization and blinded activation of NBM neurostimulation according to a 1:1 scheme.
* Visit 2 (16 weeks after randomization): motor off and on medication + stimulation state (GPi stimulation ± NBM stimulation); cognitive testing in motor on medication + stimulation state (GPi stimulation ± NBM stimulation). Activation of NBM neurostimulation in all patients.
* Visit 3 (16 weeks after activation of NBM stimulation in all patients): motor off and on medication + GPi and NBM stimulation state; cognitive testing in motor on medication + GPi and NBM stimulation state.
* Annual follow-up visit for up to 5 years after activation of NBM stimulation.

Conditions

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Parkinson Disease Mild Cognitive Impairment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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GPi stimulation + NBM stimulation

effective neurostimulation of the Nucleus basalis Meynert combined with globus pallidus internus (GPi) stimulation using Vercise deep brain stimulation

Group Type ACTIVE_COMPARATOR

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.

Intervention Type DEVICE

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM, at the same trajectory.

GPi stimulation

Intervention Type DEVICE

Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system

NBM stimulation

Intervention Type DEVICE

Bilateral low-frequency neurostimulation of the NBM using a Vercise neurostimulation system

GPi stimulation + sham stimulation

ineffective neurostimulation of the Nucleus basalis Meynert combined with subthalamic nucleus (STN) stimulation using Vercise deep brain stimulation

Group Type SHAM_COMPARATOR

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.

Intervention Type DEVICE

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM, at the same trajectory.

GPi stimulation

Intervention Type DEVICE

Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system

Sham stimulation

Intervention Type DEVICE

Ineffective neurostimulation by setting 0mA output at the Vercise neurostimulation system

Interventions

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Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.

Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM, at the same trajectory.

Intervention Type DEVICE

GPi stimulation

Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system

Intervention Type DEVICE

NBM stimulation

Bilateral low-frequency neurostimulation of the NBM using a Vercise neurostimulation system

Intervention Type DEVICE

Sham stimulation

Ineffective neurostimulation by setting 0mA output at the Vercise neurostimulation system

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Age at the time of enrollment: 50 - 75 years.
* Diagnosis of idiopathic PD according to Movement Disorders Society (MDS) criteria (Albanese et al., 2017).
* Mild cognitive impairment (MCI) related to Parkinson's disease according to MDS criteria. (Livtan et al. 2012).
* Duration of bilateral idiopathic PD: ≥ 5 years of motor symptoms.
* Modified Hoehn and Yahr stage ≥ 2 on off medication state.
* UPDRS subset III (motor) ≥ 30 points on off medication state.
* Levodopa must improve PD symptoms by ≥ 30% in a levodopa challenge test, as measured by UPDRS subset III score.
* Presence of motor complications related to Parkinson's disease.
* Be willing and able to comply with all visits and study related procedures
* Able to understand the study requirements and the treatment procedures and to provide written informed consent before any study-specific tests or procedures are performed.

Exclusion Criteria

* Alcohol or drug abuse.
* Any significant psychiatric problems, including acute confusional state (delirium), ongoing psychosis, or clinically significant depression.
* Contraindications for deep brain stimulation (DBS) surgery.
* Heart failure, heart disease or any condition that contraindicates surgical procedures.
* Pacemaker or other active implanted stimulators.
* Clearly established Parkinson's disease dementia according to Movement Disorders Criteria.
* Participation in another drug, device, or biologics trial concurrently.
Minimum Eligible Age

50 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Sao Paulo General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of São Paulo General Hospital

São Paulo, , Brazil

Site Status RECRUITING

Countries

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Brazil

Facility Contacts

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Rubens G Cury, MD, PhD

Role: primary

+551126617877

Ana Paula S Bertholo, MD

Role: backup

+5511998691919

References

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Gratwicke J, Zrinzo L, Kahan J, Peters A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Limousin P, Hariz M, Jahanshahi M, Foltynie T. Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):169-178. doi: 10.1001/jamaneurol.2017.3762.

Reference Type RESULT
PMID: 29255885 (View on PubMed)

Nombela C, Lozano A, Villanueva C, Barcia JA. Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome. Dement Geriatr Cogn Disord. 2019;47(1-2):19-28. doi: 10.1159/000493094. Epub 2019 Jan 10.

Reference Type RESULT
PMID: 30630160 (View on PubMed)

Sankar T, Lipsman N, Lozano AM. Deep brain stimulation for disorders of memory and cognition. Neurotherapeutics. 2014 Jul;11(3):527-34. doi: 10.1007/s13311-014-0275-0.

Reference Type RESULT
PMID: 24777384 (View on PubMed)

Kuhn J, Hardenacke K, Lenartz D, Gruendler T, Ullsperger M, Bartsch C, Mai JK, Zilles K, Bauer A, Matusch A, Schulz RJ, Noreik M, Buhrle CP, Maintz D, Woopen C, Haussermann P, Hellmich M, Klosterkotter J, Wiltfang J, Maarouf M, Freund HJ, Sturm V. Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia. Mol Psychiatry. 2015 Mar;20(3):353-60. doi: 10.1038/mp.2014.32. Epub 2014 May 6.

Reference Type RESULT
PMID: 24798585 (View on PubMed)

Freund HJ, Kuhn J, Lenartz D, Mai JK, Schnell T, Klosterkoetter J, Sturm V. Cognitive functions in a patient with Parkinson-dementia syndrome undergoing deep brain stimulation. Arch Neurol. 2009 Jun;66(6):781-5. doi: 10.1001/archneurol.2009.102.

Reference Type RESULT
PMID: 19506141 (View on PubMed)

Wilson J, Yarnall AJ, Craig CE, Galna B, Lord S, Morris R, Lawson RA, Alcock L, Duncan GW, Khoo TK, O'Brien JT, Burn DJ, Taylor JP, Ray NJ, Rochester L. Cholinergic Basal Forebrain Volumes Predict Gait Decline in Parkinson's Disease. Mov Disord. 2021 Mar;36(3):611-621. doi: 10.1002/mds.28453. Epub 2020 Dec 31.

Reference Type RESULT
PMID: 33382126 (View on PubMed)

Muller ML, Bohnen NI. Cholinergic dysfunction in Parkinson's disease. Curr Neurol Neurosci Rep. 2013 Sep;13(9):377. doi: 10.1007/s11910-013-0377-9.

Reference Type RESULT
PMID: 23943367 (View on PubMed)

Gratwicke J, Zrinzo L, Kahan J, Peters A, Brechany U, McNichol A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Crutch SJ, Taylor JP, McKeith I, Rochester L, Schott JM, Limousin P, Burn D, Rossor MN, Hariz M, Jahanshahi M, Foltynie T. Bilateral nucleus basalis of Meynert deep brain stimulation for dementia with Lewy bodies: A randomised clinical trial. Brain Stimul. 2020 Jul-Aug;13(4):1031-1039. doi: 10.1016/j.brs.2020.04.010. Epub 2020 Apr 22.

Reference Type RESULT
PMID: 32334074 (View on PubMed)

Dalrymple WA, Huss DS, Blair J, Flanigan JL, Patrie J, Sperling SA, Shah BB, Harrison MB, Druzgal TJ, Barrett MJ. Cholinergic nucleus 4 atrophy and gait impairment in Parkinson's disease. J Neurol. 2021 Jan;268(1):95-101. doi: 10.1007/s00415-020-10111-2. Epub 2020 Jul 28.

Reference Type RESULT
PMID: 32725313 (View on PubMed)

Koulousakis P, Andrade P, Visser-Vandewalle V, Sesia T. The Nucleus Basalis of Meynert and Its Role in Deep Brain Stimulation for Cognitive Disorders: A Historical Perspective. J Alzheimers Dis. 2019;69(4):905-919. doi: 10.3233/JAD-180133.

Reference Type RESULT
PMID: 31104014 (View on PubMed)

Other Identifiers

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38865720.1.0000.0068

Identifier Type: -

Identifier Source: org_study_id

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