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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| GPi stimulation + sham stimulation | Sham Comparator | ineffective neurostimulation of the Nucleus basalis Meynert combined with subthalamic nucleus (STN) stimulation using Vercise deep brain stimulation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Parkinson's Disease - Cognitive Rating Scale (PD-CRS). | This scale can range from 0 to 134, and higher scores mean a better outcome. | 36 weeks |
| Change in Mattis Dementia Rating Scale. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of São Paulo General Hospital | Recruiting | São Paulo | 05403000 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29255885 | Result | 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. | |
| 30630160 |
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| GPi stimulation | Device | Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system |
|
| NBM stimulation | Device | Bilateral low-frequency neurostimulation of the NBM using a Vercise neurostimulation system |
|
| Sham stimulation | Device | Ineffective neurostimulation by setting 0mA output at the Vercise neurostimulation system |
|
This scale can range from 0 to 144, and higher scores mean a better outcome.
| 36 weeks |
| Change in Verbal Fluency Battery. | FAS and animals | 36 weeks |
| Change in Trail Making Task. | Trail Making Task Part A + B. | 36 weeks |
| Change in Stroop Test. | Stroop Test (Victoria Version). | 36 weeks |
| Change in Symbol Digit Modalities Test. | Digit symbol coding - WAIS. | 36 weeks |
| Change in Parkinson's Disease Questionnaire for quality of life (PDQ-39). | This questionnaire can range from 0 to 100%, and higher scores mean a worse outcome. | 36 weeks |
| Change in Questionnaire of the EuroQol-group (EQ-5D-5L). | This questionnaire can range from 0 to 25, and higher scores mean a worse outcome. | 36 weeks |
| Change in Unified Parkinson's Disease Rating Scale section I (UPDRS I). | This scale can range from 0 to 52, and higher scores mean a worse outcome. | 36 weeks |
| Change in Unified Parkinson's Disease Rating Scale section II (UPDRS II). | This scale can range from 0 to 52, and higher scores mean a worse outcome. | 36 weeks |
| Change in Unified Parkinson's Disease Rating Scale section III (UPDRS III). | This scale can range from 0 to 132, and higher scores mean a worse outcome. | 36 weeks |
| Change in Unified Parkinson's Disease Rating Scale section IV (UPDRS IV). | This scale can range from 0 to 24, and higher scores mean a worse outcome. | 36 weeks |
| Change in objective assessment of gait measured by a sensor (MobilityLab) that assess step speed. | 36 weeks |
| Change in objective assessment of gait measured by a sensor (MobilityLab) that assess number of steps per minute. | 36 weeks |
| Change in objective assessment of gait measured by a sensor (MobilityLab) that assess distance between heels. | 36 weeks |
| Change in objective assessment of gait measured by a sensor (MobilityLab) that assess balance. | 36 weeks |
| Change in objective assessment of gait measured by Time Up and Go - Test 3 meters (TUG test 3M). | 36 weeks |
| Change in objective assessment of gait measured by Time Up and Go dual task - Test 3 meters (TUG dual task - test 3M). | 36 weeks |
| Change in objective assessment of gait measured by freezing of gait score (FOG score). | 36 weeks |
| Change in New Freezing of Gait Questionnaire (N-FOG). | This questionnaire can range from 0 to 28, and higher scores mean a worse outcome. | 36 weeks |
| Change in Falls Efficacy Scale International (FES-I). | This questionnaire can range from 0 to 64, and higher scores mean a worse outcome. | 36 weeks |
| Change in Activities-Specific Balance Confidence Scale (ABC scale). | This scale can range from 0 to 100%, and higher scores mean a better outcome. | 36 weeks |
| Change in Beck Depression Inventory (BDI). | This inventory can range from 0 to 63, and higher scores mean a worse outcome. | 36 weeks |
| Change in Beck Anxiety Inventory (BAI). | This inventory can range from 0 to 63, and higher scores mean a worse outcome. | 36 weeks |
| Change in Starkstein Apathy Scale. | This scale can range from 0 to 42, and higher scores mean a worse outcome. | 36 weeks |
| Change in Neuropsychiatric Inventory (NPI). | 36 weeks |
| Change in Ardouin Scale of Behavior in Parkinson's Disease. | This scale can range from 0 to 84, and higher scores mean a worse outcome. | 36 weeks |
| 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. |
| 24777384 | Result | 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. |
| 24798585 | Result | 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. |
| 19506141 | Result | 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. |
| 33382126 | Result | 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. |
| 23943367 | Result | 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. |
| 32334074 | Result | 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. |
| 32725313 | Result | 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. |
| 31104014 | Result | 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. |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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