NCT05320523

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
10

participants targeted

Target at below P25 for not_applicable parkinson-disease

Timeline
Completed

Started Jul 2021

Typical duration for not_applicable parkinson-disease

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 20, 2021

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

March 14, 2022

Completed
28 days until next milestone

First Posted

Study publicly available on registry

April 11, 2022

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2023

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2024

Completed
Last Updated

April 11, 2022

Status Verified

October 1, 2021

Enrollment Period

2 years

First QC Date

March 14, 2022

Last Update Submit

April 1, 2022

Conditions

Parkinson DiseaseMild Cognitive Impairment

Keywords

Parkinson's diseaseMild cognitive impairmentGlobus Pallidus internus (GPi) StimulationNucleus basalis of Meynert (NBM) StimulationDeep Brain Stimulation (DBS)

Outcome Measures

Primary Outcomes (1)

  • Safety of combined bilateral Globus Pallidus internus (GPi) and Nucleus Basalis of Meynert (NBM) stimulation in patients with moderate to advanced Parkinson's disease with mild cognitive impairment as determined by reported adverse events.

    Safety of combined bilateral GPi and NBM stimulation in patients with moderate to advanced Parkinson's disease having mild cognitive impairment as determined by reported adverse events.

    36 weeks

Secondary Outcomes (27)

  • Change in Parkinson's Disease - Cognitive Rating Scale (PD-CRS).

    36 weeks

  • Change in Mattis Dementia Rating Scale.

    36 weeks

  • Change in Verbal Fluency Battery.

    36 weeks

  • Change in Trail Making Task.

    36 weeks

  • Change in Stroop Test.

    36 weeks

  • +22 more secondary outcomes

Study Arms (2)

GPi stimulation + NBM stimulation

ACTIVE COMPARATOR

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

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

GPi stimulation + sham stimulation

SHAM COMPARATOR

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

Device: Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM.Device: GPi stimulationDevice: Sham stimulation

Interventions

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

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

GPi stimulation + NBM stimulationGPi stimulation + sham stimulation
GPi stimulationDEVICE

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

GPi stimulation + NBM stimulationGPi stimulation + sham stimulation
NBM stimulationDEVICE

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

GPi stimulation + NBM stimulation
Sham stimulationDEVICE

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

GPi stimulation + sham stimulation

Eligibility Criteria

Age50 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of São Paulo General Hospital

São Paulo, 05403000, Brazil

RECRUITING

Related Publications (10)

  • 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.

    PMID: 29255885RESULT

  • 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.

    PMID: 30630160RESULT

  • 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.

    PMID: 24777384RESULT

  • 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.

    PMID: 24798585RESULT

  • 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.

    PMID: 19506141RESULT

  • 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.

    PMID: 33382126RESULT

  • 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.

    PMID: 23943367RESULT

  • 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.

    PMID: 32334074RESULT

  • 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.

    PMID: 32725313RESULT

  • 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.

    PMID: 31104014RESULT

MeSH Terms

Conditions

Parkinson DiseaseCognitive Dysfunction

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative DiseasesCognition DisordersNeurocognitive DisordersMental Disorders

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2022

First Posted

April 11, 2022

Study Start

July 20, 2021

Primary Completion

August 1, 2023

Study Completion

January 1, 2024

Last Updated

April 11, 2022

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will not share

Locations

BR(1)