Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of California, Los Angeles | OTHER |
| University of Florida | OTHER |
| University Health Network, Toronto | OTHER |
| The Cleveland Clinic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to determine if repetitive transcranial magnetic stimulation (rTMS), a method of noninvasive brain stimulation) is effective in the treatment of the motor (movement) and mood symptoms due to Parkinson's disease (PD).
Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive means of brain stimulation which can produce changes to brain excitability. Following a series of daily rTMS sessions, this modulation of neural circuits and other distant effects may help some of the motor and neuropsychiatric symptoms of PD for months at a time. Recently, the FDA approved daily rTMS over the prefrontal cortex as a treatment for medication-refractory depression after demonstration of efficacy in sham-controlled trials and its safety profile. Among several small and pilot studies of rTMS in PD patients, rTMS over either the motor cortex or prefrontal cortex has been reported to show beneficial effects on motor and mood (depression) symptoms with no serious adverse events. However, the relative effectiveness of rTMS over motor, prefrontal, or both regions on both mood and motor symptoms, has yet to be established in PD patients.
We propose to conduct a four-center, blinded, sham-controlled, randomized, parallel-group study of fixed-dose, high-frequency rTMS in 160 PD patients who are experiencing depressive symptoms despite an adequate trial of at least one antidepressant. Subjects will be randomized to receive rTMS over either motor cortex, prefrontal cortex, both, or neither (sham-rTMS). Subjects will receive rTMS for 25 minutes over either the prefrontal cortex (the brain region associated with mood and depression), and/or primary motor cortex (associated with motor control), and/or sham-rTMS. After 10 days of rTMS (or sham) treatment over a 2-week period, all subjects will undergo a comprehensive assessment of motor, mood, cognition and quality of life on the first working day after the last rTMS treatment, and after 1, 3 and 6 months post-treatment. This study directly addresses the expansion of rTMS as an alternative treatment for depression in the PD population and will provide evidence as to whether motor cortex stimulation will provide additional and/or separate benefit to motor symptoms.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Double rTMS | Active Comparator | High frequency rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). |
|
| M1 Active rTMS + DLPFC Sham rTMS | Active Comparator | High frequency stimulation of the primary motor cortex (M1) and sham stimulation of the dorsolateral prefrontal cortex (DLPFC). |
|
| DLPFC Active rTMS + M1 Sham rTMS | Active Comparator | High frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) and sham stimulation of the primary motor cortex (M1). |
|
| Double Sham rTMS | Sham Comparator | Sham rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Repetitive transcranial magnetic stimulation (rTMS) | Device | DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| Measure | Description | Time Frame |
|---|---|---|
| Motor Subscale of the Unified Parkinson's Disease Rating Scale (UPDRS Part III) | To evaluate the motor symptoms in Parkinson's Disease. The UPDRS-III mean scores were reported for each group at each time point. The UPDRS-III Score Range is 0 - 56, where higher the score indicates greater severity of the motor symptoms. | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| Hamilton Depression Scale (HAM-D) | To evaluate the depressive mood symptoms in PD. The HAM-D mean scores were reported for each group at each time point. The HAM-D Score Range is 0 - 56, where higher the score indicates greater severity of depressive mood symptoms. | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Anxiety Scale (CAS) | To evaluate anxiety in Parkinson's Disease. The CAS mean scores were reported for each group at each time point. The CAS Score Range is 0 - 100, where higher the score indicates greater severity of the anxiety symptoms. | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| Apathy Evaluation Scale (AES) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Alvaro Pascual-Leone, M.D., Ph.D. | Beth Israel Deaconess Medical Center | Principal Investigator |
| Allan Wu, M.D. | University of California, Los Angeles | Principal Investigator |
| Hubert Fernandez, M.D. | The Cleveland Clinic | Principal Investigator |
| Robert Chen, BChir, MA, MB, MSc | University Health Network, Toronto | Principal Investigator |
| Aparna Wagle-Shukla, MD | University of Florida | Principal Investigator |
| Jau-Shin Lou, MD, PhD | Oregon Health and Science University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Los Angeles | Los Angeles | California | United States | |||
| University of Florida |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15822106 | Background | Adler CH. Nonmotor complications in Parkinson's disease. Mov Disord. 2005;20 Suppl 11:S23-9. doi: 10.1002/mds.20460. | |
| 13688369 | Background | BECK AT, WARD CH, MENDELSON M, MOCK J, ERBAUGH J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 Jun;4:561-71. doi: 10.1001/archpsyc.1961.01710120031004. No abstract available. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
We enrolled 61 subjects into this study with a previous enrollment goal of 85. Interim analysis revealed that 61 subjects provided sufficient power for data analysis, therefore we stopped recruitment.
Subjects were screened and enrolled from 6 clinical centers in the United States and 1 clinical center in Canada.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Double rTMS | High frequency rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| FG001 | M1 Active rTMS + DLPFC Sham rTMS | High frequency stimulation of the primary motor cortex (M1) and sham stimulation of the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| FG002 | DLPFC Active rTMS + M1 Sham rTMS | High frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) and sham stimulation of the primary motor cortex (M1). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| FG003 | Double Sham rTMS | Sham rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Double rTMS | High frequency rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Motor Subscale of the Unified Parkinson's Disease Rating Scale (UPDRS Part III) | To evaluate the motor symptoms in Parkinson's Disease. The UPDRS-III mean scores were reported for each group at each time point. The UPDRS-III Score Range is 0 - 56, where higher the score indicates greater severity of the motor symptoms. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
Baseline through 6 months post-treatment.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Double rTMS | High frequency rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stroke | Nervous system disorders | Determined to be unrelated to the study by overseeing physician. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Worsened Depression | Psychiatric disorders | Determined to be unrelated to the study by overseeing physician. |
The study did not reach the enrollment goal of 120 patients reducing the statistical power of the study. Additionally, patients with mild and advanced disease with variable years of drug exposure were enrolled, which may obscure effects in subgroups.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Alvaro Pascual-Leone | Beth Israel Deaconess Medical Center | (617) 667-0203 | apleone@bidmc.harvard.edu |
Not provided
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D003863 | Depression |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
| OTHER |
| Michael J. Fox Foundation for Parkinson's Research | OTHER |
Not provided
Not provided
Not provided
Not provided
|
|
To evaluate apathy in Parkinson's Disease. The AES mean scores were reported for each group at each time point. The AES Score Range is 0-42, where higher the score indicates greater severity of the apathy symptoms. |
| Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| Parkinson's Disease Questionnaire 39 (PDQ-39) | To assess the quality of life (QOL) in Parkinson's Disease. The PDQ-39 mean scores were reported for each group at each time point. The PDQ-39 Score Range is 0 - 156, where higher the score indicates greater impact on quality of life. | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| Montreal Cognitive Assessment (MoCA) | To screen and follow cognitive function in Parkinson's Disease. The MoCA mean scores were reported for each group at each time point. The MoCA Score Range is 0 - 30, where 26-30 indicates normal cognition. | pre-treatment; 0,1,3, and 6 months post-treatment |
| Unified Parkinson's Disease Rating Scale (UPDRS) Parts I, II, and IV | To assess apathy, cognition, depression, activities of daily living (ADL), quality of life (QOL), and motor symptoms in Parkinson's Disease. The UPDRS I, II, IV total mean scores were reported for each group at each time point. The UPDRS I, II, IV scores were added together for each patient, with a total score range of 0 - 91, where higher the score indicates greater severity of the symptoms. | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| Beck Depression Inventory (BDI-II) | To assess mood symptoms in Parkinson's Disease. The BDI-II mean scores were reported for each group at each time point. The BDI-II Score Range is 0 - 63, where higher the score indicates greater severity of the mood symptoms. | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| Global Impression Scales | To assess symptom severity and treatment response in Parkinson's Disease. The CGI mean scores were reported for each group at each time point. The CGI Score Range is 1 - 8, where higher the score indicates greater severity of illness or worsening of illness. | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
| The Number All Types of Adverse Events. | To establish the safety and tolerability of rTMS in Parkinson's Disease. | Baseline through Month 6 |
| Gainesville |
| Florida |
| United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| The Cleveland Clinic | Cleveland | Ohio | United States |
| Oregon Health and Science University | Portland | Oregon | United States |
| University Health Network | Toronto | Ontario | Canada |
| 16280671 | Background | Benabid AL, Chabardes S, Seigneuret E. Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety - What happened this year? Curr Opin Neurol. 2005 Dec;18(6):623-30. doi: 10.1097/01.wco.0000186839.53807.93. |
| 15354390 | Background | Bornke Ch, Schulte T, Przuntek H, Muller T. Clinical effects of repetitive transcranial magnetic stimulation versus acute levodopa challenge in Parkinson's disease. J Neural Transm Suppl. 2004;(68):61-7. doi: 10.1007/978-3-7091-0579-5_7. |
| 16887383 | Background | Brusa L, Versace V, Koch G, Iani C, Stanzione P, Bernardi G, Centonze D. Low frequency rTMS of the SMA transiently ameliorates peak-dose LID in Parkinson's disease. Clin Neurophysiol. 2006 Sep;117(9):1917-21. doi: 10.1016/j.clinph.2006.03.033. Epub 2006 Aug 1. |
| 15509619 | Background | Buhmann C, Gorsler A, Baumer T, Hidding U, Demiralay C, Hinkelmann K, Weiller C, Siebner HR, Munchau A. Abnormal excitability of premotor-motor connections in de novo Parkinson's disease. Brain. 2004 Dec;127(Pt 12):2732-46. doi: 10.1093/brain/awh321. Epub 2004 Oct 27. |
| 15312281 | Background | Burn DJ, Troster AI. Neuropsychiatric complications of medical and surgical therapies for Parkinson's disease. J Geriatr Psychiatry Neurol. 2004 Sep;17(3):172-80. doi: 10.1177/0891988704267466. |
| 12057034 | Background | Burt T, Lisanby SH, Sackeim HA. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol. 2002 Mar;5(1):73-103. doi: 10.1017/S1461145702002791. |
| 12436085 | Background | Cantello R. Applications of transcranial magnetic stimulation in movement disorders. J Clin Neurophysiol. 2002 Aug;19(4):272-93. doi: 10.1097/00004691-200208000-00003. |
| 17708780 | Background | Cardoso EF, Fregni F, Martins Maia F, Boggio PS, Luis Myczkowski M, Coracini K, Lopes Vieira A, Melo LM, Sato JR, Antonio Marcolin M, Rigonatti SP, Cruz AC Jr, Reis Barbosa E, Amaro E Jr. rTMS treatment for depression in Parkinson's disease increases BOLD responses in the left prefrontal cortex. Int J Neuropsychopharmacol. 2008 Mar;11(2):173-83. doi: 10.1017/S1461145707007961. Epub 2007 Aug 21. |
| 16488379 | Background | Chaudhuri KR, Healy DG, Schapira AH; National Institute for Clinical Excellence. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006 Mar;5(3):235-45. doi: 10.1016/S1474-4422(06)70373-8. |
| 9121622 | Background | Conca A, Koppi S, Konig P, Swoboda E, Krecke N. Transcranial magnetic stimulation: a novel antidepressive strategy? Neuropsychobiology. 1996;34(4):204-7. doi: 10.1159/000119312. |
| 2871792 | Background | Crow TJ, Johnstone EC. Controlled trials of electroconvulsive therapy. Ann N Y Acad Sci. 1986;462:12-29. doi: 10.1111/j.1749-6632.1986.tb51235.x. No abstract available. |
| 12197850 | Background | Aarsland D, Cummings JL. Depression in Parkinson's disease. Acta Psychiatr Scand. 2002 Sep;106(3):161-2. doi: 10.1034/j.1600-0447.2002.2e009.x. No abstract available. |
| 17097342 | Background | del Olmo MF, Bello O, Cudeiro J. Transcranial magnetic stimulation over dorsolateral prefrontal cortex in Parkinson's disease. Clin Neurophysiol. 2007 Jan;118(1):131-9. doi: 10.1016/j.clinph.2006.09.002. Epub 2006 Nov 9. |
| 16411969 | Background | Dias AE, Barbosa ER, Coracini K, Maia F, Marcolin MA, Fregni F. Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson's disease. Acta Neurol Scand. 2006 Feb;113(2):92-9. doi: 10.1111/j.1600-0404.2005.00558.x. |
| 12112202 | Background | Dragasevic N, Potrebic A, Damjanovic A, Stefanova E, Kostic VS. Therapeutic efficacy of bilateral prefrontal slow repetitive transcranial magnetic stimulation in depressed patients with Parkinson's disease: an open study. Mov Disord. 2002 May;17(3):528-32. doi: 10.1002/mds.10109. |
| 18972549 | Background | Elahi B, Elahi B, Chen R. Effect of transcranial magnetic stimulation on Parkinson motor function--systematic review of controlled clinical trials. Mov Disord. 2009 Feb 15;24(3):357-63. doi: 10.1002/mds.22364. |
| 9736466 | Background | Epstein CM. Transcranial magnetic stimulation: language function. J Clin Neurophysiol. 1998 Jul;15(4):325-32. doi: 10.1097/00004691-199807000-00004. |
| 17714987 | Background | Epstein CM, Evatt ML, Funk A, Girard-Siqueira L, Lupei N, Slaughter L, Athar S, Green J, McDonald W, DeLong MR. An open study of repetitive transcranial magnetic stimulation in treatment-resistant depression with Parkinson's disease. Clin Neurophysiol. 2007 Oct;118(10):2189-94. doi: 10.1016/j.clinph.2007.07.010. Epub 2007 Aug 21. |
| 1471873 | Background | Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. Ann Neurol. 1992 Dec;32(6):804-12. doi: 10.1002/ana.410320616. |
| 19429848 | Background | Fernandez HH, See RH, Gary MF, Bowers D, Rodriguez RL, Jacobson C 4th, Okun MS. Depressive symptoms in Parkinson disease correlate with impaired global and specific cognitive performance. J Geriatr Psychiatry Neurol. 2009 Dec;22(4):223-7. doi: 10.1177/0891988709335792. Epub 2009 May 8. |
| 11748746 | Background | Fernandez HH, Tabamo RE, David RR, Friedman JH. Predictors of depressive symptoms among spouse caregivers in Parkinson's disease. Mov Disord. 2001 Nov;16(6):1123-5. doi: 10.1002/mds.1196. |
| 9547462 | Background | Figiel GS, Epstein C, McDonald WM, Amazon-Leece J, Figiel L, Saldivia A, Glover S. The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory depressed patients. J Neuropsychiatry Clin Neurosci. 1998 Winter;10(1):20-5. doi: 10.1176/jnp.10.1.20. |
| 8166303 | Background | Flint AJ. Epidemiology and comorbidity of anxiety disorders in the elderly. Am J Psychiatry. 1994 May;151(5):640-9. doi: 10.1176/ajp.151.5.640. |
| 15258224 | Background | Fregni F, Santos CM, Myczkowski ML, Rigolino R, Gallucci-Neto J, Barbosa ER, Valente KD, Pascual-Leone A, Marcolin MA. Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1171-4. doi: 10.1136/jnnp.2003.027060. |
| 16291882 | Background | Fregni F, Simon DK, Wu A, Pascual-Leone A. Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature. J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1614-23. doi: 10.1136/jnnp.2005.069849. |
| Background | Friedman JH, Fernandez HH. The nonmotor problems of Parkinson's Disease. The Neurologist 6(1): 18-27, 2000. |
| 9396958 | Background | George MS, Wassermann EM, Kimbrell TA, Little JT, Williams WE, Danielson AL, Greenberg BD, Hallett M, Post RM. Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial. Am J Psychiatry. 1997 Dec;154(12):1752-6. doi: 10.1176/ajp.154.12.1752. |
| 8547583 | Background | George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008. |
| 12727683 | Background | Gershon AA, Dannon PN, Grunhaus L. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003 May;160(5):835-45. doi: 10.1176/appi.ajp.160.5.835. |
| 10078725 | Background | Ghabra MB, Hallett M, Wassermann EM. Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD. Neurology. 1999 Mar 10;52(4):768-70. doi: 10.1212/wnl.52.4.768. |
| 18381646 | Background | Gill DJ, Freshman A, Blender JA, Ravina B. The Montreal cognitive assessment as a screening tool for cognitive impairment in Parkinson's disease. Mov Disord. 2008 May 15;23(7):1043-1046. doi: 10.1002/mds.22017. |
| 15582373 | Background | Grafton ST. Contributions of functional imaging to understanding parkinsonian symptoms. Curr Opin Neurobiol. 2004 Dec;14(6):715-9. doi: 10.1016/j.conb.2004.10.010. |
| 12686400 | Background | Ikeguchi M, Touge T, Nishiyama Y, Takeuchi H, Kuriyama S, Ohkawa M. Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. J Neurol Sci. 2003 May 15;209(1-2):41-6. doi: 10.1016/s0022-510x(02)00459-8. |
| 12940840 | Background | Khedr EM, Farweez HM, Islam H. Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson's disease patients. Eur J Neurol. 2003 Sep;10(5):567-72. doi: 10.1046/j.1468-1331.2003.00649.x. |
| 17097343 | Background | Khedr EM, Rothwell JC, Ahmed MA, Shawky OA, Farouk M. Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation. Clin Neurophysiol. 2007 Jan;118(1):140-5. doi: 10.1016/j.clinph.2006.09.006. Epub 2006 Nov 9. |
| 16832074 | Background | Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D. Dissociating apathy and depression in Parkinson disease. Neurology. 2006 Jul 11;67(1):33-8. doi: 10.1212/01.wnl.0000230572.07791.22. |
| 7931395 | Background | Kostic VS, Filipovic SR, Lecic D, Momcilovic D, Sokic D, Sternic N. Effect of age at onset on frequency of depression in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1994 Oct;57(10):1265-7. doi: 10.1136/jnnp.57.10.1265. |
| 9153482 | Background | Krings T, Buchbinder BR, Butler WE, Chiappa KH, Jiang HJ, Cosgrove GR, Rosen BR. Functional magnetic resonance imaging and transcranial magnetic stimulation: complementary approaches in the evaluation of cortical motor function. Neurology. 1997 May;48(5):1406-16. doi: 10.1212/wnl.48.5.1406. |
| 15099546 | Background | Lang AE, Obeso JA. Challenges in Parkinson's disease: restoration of the nigrostriatal dopamine system is not enough. Lancet Neurol. 2004 May;3(5):309-16. doi: 10.1016/S1474-4422(04)00740-9. |
| 15312275 | Background | Leentjens AF. Depression in Parkinson's disease: conceptual issues and clinical challenges. J Geriatr Psychiatry Neurol. 2004 Sep;17(3):120-6. doi: 10.1177/0891988704267456. |
| 16205779 | Background | Leentjens AF, Scholtissen B, Vreeling FW, Verhey FR. The serotonergic hypothesis for depression in Parkinson's disease: an experimental approach. Neuropsychopharmacology. 2006 May;31(5):1009-15. doi: 10.1038/sj.npp.1300914. |
| 15465443 | Background | Lefaucheur JP, Drouot X, Von Raison F, Menard-Lefaucheur I, Cesaro P, Nguyen JP. Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease. Clin Neurophysiol. 2004 Nov;115(11):2530-41. doi: 10.1016/j.clinph.2004.05.025. |
| 15675721 | Background | Lemke MR, Fuchs G, Gemende I, Herting B, Oehlwein C, Reichmann H, Rieke J, Volkmann J. Depression and Parkinson's disease. J Neurol. 2004 Sep;251 Suppl 6:VI/24-7. doi: 10.1007/s00415-004-1606-6. |
| 3236018 | Background | Levin BE, Llabre MM, Weiner WJ. Parkinson's disease and depression: psychometric properties of the Beck Depression Inventory. J Neurol Neurosurg Psychiatry. 1988 Nov;51(11):1401-4. doi: 10.1136/jnnp.51.11.1401. |
| 17576282 | Background | Lieberman MD, Eisenberger NI, Crockett MJ, Tom SM, Pfeifer JH, Way BM. Putting feelings into words: affect labeling disrupts amygdala activity in response to affective stimuli. Psychol Sci. 2007 May;18(5):421-8. doi: 10.1111/j.1467-9280.2007.01916.x. |
| 9309555 | Background | Liu CY, Wang SJ, Fuh JL, Lin CH, Yang YY, Liu HC. The correlation of depression with functional activity in Parkinson's disease. J Neurol. 1997 Aug;244(8):493-8. doi: 10.1007/s004150050131. |
| 16211618 | Background | Lomarev MP, Kanchana S, Bara-Jimenez W, Iyer M, Wassermann EM, Hallett M. Placebo-controlled study of rTMS for the treatment of Parkinson's disease. Mov Disord. 2006 Mar;21(3):325-31. doi: 10.1002/mds.20713. |
| 11521156 | Background | Maeda F, Chang VY, Mazziotta J, Iacoboni M. Experience-dependent modulation of motor corticospinal excitability during action observation. Exp Brain Res. 2001 Sep;140(2):241-4. doi: 10.1007/s002210100827. |
|
| 10985677 | Background | Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A. Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability. Exp Brain Res. 2000 Aug;133(4):425-30. doi: 10.1007/s002210000432. |
| 15464863 | Background | Mally J, Farkas R, Tothfalusi L, Stone TW. Long-term follow-up study with repetitive transcranial magnetic stimulation (rTMS) in Parkinson's disease. Brain Res Bull. 2004 Sep 30;64(3):259-63. doi: 10.1016/j.brainresbull.2004.07.004. |
| 1821241 | Background | Marin RS. Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci. 1991 Summer;3(3):243-54. doi: 10.1176/jnp.3.3.243. |
| 2001183 | Background | Mayeux R, Sano M, Chen J, Tatemichi T, Stern Y. Risk of dementia in first-degree relatives of patients with Alzheimer's disease and related disorders. Arch Neurol. 1991 Mar;48(3):269-73. doi: 10.1001/archneur.1991.00530150037014. |
| 6200801 | Background | Mayeux R, Stern Y, Cote L, Williams JB. Altered serotonin metabolism in depressed patients with parkinson's disease. Neurology. 1984 May;34(5):642-6. doi: 10.1212/wnl.34.5.642. |
| 2424323 | Background | Mayeux R, Stern Y, Williams JB, Cote L, Frantz A, Dyrenfurth I. Clinical and biochemical features of depression in Parkinson's disease. Am J Psychiatry. 1986 Jun;143(6):756-9. doi: 10.1176/ajp.143.6.756. |
| 20160893 | Background | Mennemeier M, Triggs W, Chelette K, Woods A, Kimbrell T, Dornhoffer J. Sham Transcranial Magnetic Stimulation Using Electrical Stimulation of the Scalp. Brain Stimul. 2009 Jul 1;2(3):168-173. doi: 10.1016/j.brs.2009.02.002. |
| 17266084 | Background | Miller KM, Okun MS, Fernandez HF, Jacobson CE 4th, Rodriguez RL, Bowers D. Depression symptoms in movement disorders: comparing Parkinson's disease, dystonia, and essential tremor. Mov Disord. 2007 Apr 15;22(5):666-72. doi: 10.1002/mds.21376. |
| 15955942 | Background | Mir P, Matsunaga K, Gilio F, Quinn NP, Siebner HR, Rothwell JC. Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease. Neurology. 2005 Jun 14;64(11):1906-12. doi: 10.1212/01.WNL.0000163772.56128.A8. |
| 15817019 | Background | Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. |
| 17573044 | Background | O'Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, McDonald WM, Avery D, Fitzgerald PB, Loo C, Demitrack MA, George MS, Sackeim HA. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007 Dec 1;62(11):1208-16. doi: 10.1016/j.biopsych.2007.01.018. Epub 2007 Jun 14. |
| 12671943 | Background | Okabe S, Ugawa Y, Kanazawa I; Effectiveness of rTMS on Parkinson's Disease Study Group. 0.2-Hz repetitive transcranial magnetic stimulation has no add-on effects as compared to a realistic sham stimulation in Parkinson's disease. Mov Disord. 2003 Apr;18(4):382-8. doi: 10.1002/mds.10370. |
| 8684201 | Background | Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6. |
| 8190293 | Background | Pascual-Leone A, Valls-Sole J, Brasil-Neto JP, Cammarota A, Grafman J, Hallett M. Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. Neurology. 1994 May;44(5):892-8. doi: 10.1212/wnl.44.5.892. |
| 11703468 | Background | Paus T, Castro-Alamancos MA, Petrides M. Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation. Eur J Neurosci. 2001 Oct;14(8):1405-11. doi: 10.1046/j.0953-816x.2001.01757.x. |
| 15291663 | Background | Piasecki SD, Jefferson JW. Psychiatric complications of deep brain stimulation for Parkinson's disease. J Clin Psychiatry. 2004 Jun;65(6):845-9. doi: 10.4088/jcp.v65n0617. |
| 15718222 | Background | Rickards H. Depression in neurological disorders: Parkinson's disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry. 2005 Mar;76 Suppl 1(Suppl 1):i48-52. doi: 10.1136/jnnp.2004.060426. No abstract available. |
| 14614806 | Background | Robertson EM, Theoret H, Pascual-Leone A. Studies in cognition: the problems solved and created by transcranial magnetic stimulation. J Cogn Neurosci. 2003 Oct 1;15(7):948-60. doi: 10.1162/089892903770007344. |
| Background | Sackheim HA. The cognitive effectsd of electroconvulsive therapy. Cognitive Disorders: Pathophysiology and Treatment. Moos WH and Gamzu ER. New York, Marcel Decker: 183-228, 1992. |
| 15109585 | Background | Sawabini KA, Watts RL. Treatment of depression in Parkinson's disease. Parkinsonism Relat Disord. 2004 May;10 Suppl 1:S37-41. doi: 10.1016/j.parkreldis.2004.02.002. |
| 3394854 | Background | Schiffer RB, Kurlan R, Rubin A, Boer S. Evidence for atypical depression in Parkinson's disease. Am J Psychiatry. 1988 Aug;145(8):1020-2. doi: 10.1176/ajp.145.8.1020. |
| 10636177 | Background | Siebner HR. Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD. Neurology. 2000 Jan 11;54(1):272; author reply 273. doi: 10.1212/wnl.54.1.272-a. No abstract available. |
| 12937071 | Background | Siebner HR, Filipovic SR, Rowe JB, Cordivari C, Gerschlager W, Rothwell JC, Frackowiak RS, Bhatia KP. Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. Brain. 2003 Dec;126(Pt 12):2710-25. doi: 10.1093/brain/awg282. Epub 2003 Aug 22. |
| 10208595 | Background | Siebner HR, Mentschel C, Auer C, Conrad B. Repetitive transcranial magnetic stimulation has a beneficial effect on bradykinesia in Parkinson's disease. Neuroreport. 1999 Feb 25;10(3):589-94. doi: 10.1097/00001756-199902250-00027. |
| 7150890 | Background | Snaith RP, Baugh SJ, Clayden AD, Husain A, Sipple MA. The Clinical Anxiety Scale: an instrument derived from the Hamilton Anxiety Scale. Br J Psychiatry. 1982 Nov;141:518-23. doi: 10.1192/bjp.141.5.518. No abstract available. |
| 3235647 | Background | Squire LR, Zouzounis JA. Self-ratings of memory dysfunction: different findings in depression and amnesia. J Clin Exp Neuropsychol. 1988 Dec;10(6):727-38. doi: 10.1080/01688638808402810. |
| Background | Stallings LE, Speer AM, et al. Combining SPECT and repetitive transcranial magnetic stimulation (rTMS)-left prefrontal stimulation decreases relative perfusion locally in a dose dependent manner. Neuroimage 5: S521 Abstract, 1997. |
| 1627973 | Background | Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG. Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 1992 Spring;4(2):134-9. doi: 10.1176/jnp.4.2.134. |
| 2266368 | Background | Starkstein SE, Preziosi TJ, Forrester AW, Robinson RG. Specificity of affective and autonomic symptoms of depression in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1990 Oct;53(10):869-73. doi: 10.1136/jnnp.53.10.869. |
| 11459878 | Background | Strafella AP, Paus T, Barrett J, Dagher A. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci. 2001 Aug 1;21(15):RC157. doi: 10.1523/JNEUROSCI.21-15-j0003.2001. |
| 12937078 | Background | Strafella AP, Paus T, Fraraccio M, Dagher A. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain. 2003 Dec;126(Pt 12):2609-15. doi: 10.1093/brain/awg268. Epub 2003 Aug 22. |
| Background | Talairach J, Tournoux P. Co-planar Stereotaxic Atlas of the Human Brain. New York, Thieme Medical Publishers, Inc. 1988. |
| 10090656 | Background | Tergau F, Wanschura V, Canelo M, Wischer S, Wassermann EM, Ziemann U, Paulus W. Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation. Exp Brain Res. 1999 Feb;124(4):447-54. doi: 10.1007/s002210050640. |
| 10590961 | Background | Tergau F, Wassermann EM, Paulus W, Ziemann U. Lack of clinical improvement in patients with Parkinson's disease after low and high frequency repetitive transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol Suppl. 1999;51:281-8. No abstract available. |
| Background | Tormos JM, Catala MD, et al. Effects of repetitive transcranial magnetic stimulation (rTMS) on EEG. Neurology 50: A317-A318 Abstract, 1998. |
| 10356626 | Background | Triggs WJ, McCoy KJ, Greer R, Rossi F, Bowers D, Kortenkamp S, Nadeau SE, Heilman KM, Goodman WK. Effects of left frontal transcranial magnetic stimulation on depressed mood, cognition, and corticomotor threshold. Biol Psychiatry. 1999 Jun 1;45(11):1440-6. doi: 10.1016/s0006-3223(99)00031-1. |
| 15688174 | Background | Valero-Cabre A, Payne BR, Rushmore J, Lomber SG, Pascual-Leone A. Impact of repetitive transcranial magnetic stimulation of the parietal cortex on metabolic brain activity: a 14C-2DG tracing study in the cat. Exp Brain Res. 2005 May;163(1):1-12. doi: 10.1007/s00221-004-2140-6. Epub 2005 Feb 2. |
| 16179652 | Background | Veazey C, Aki SO, Cook KF, Lai EC, Kunik ME. Prevalence and treatment of depression in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2005 Summer;17(3):310-23. doi: 10.1176/jnp.17.3.310. |
| 9345470 | Background | Wassermann EM, Wang B, Zeffiro TA, Sadato N, Pascual-Leone A, Toro C, Hallett M. Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET. Neuroimage. 1996 Feb;3(1):1-9. doi: 10.1006/nimg.1996.0001. |
| 18394576 | Background | Wu AD, Fregni F, Simon DK, Deblieck C, Pascual-Leone A. Noninvasive brain stimulation for Parkinson's disease and dystonia. Neurotherapeutics. 2008 Apr;5(2):345-61. doi: 10.1016/j.nurt.2008.02.002. |
| 17349813 | Background | Ziemssen T, Reichmann H. Non-motor dysfunction in Parkinson's disease. Parkinsonism Relat Disord. 2007 Aug;13(6):323-32. doi: 10.1016/j.parkreldis.2006.12.014. Epub 2007 Mar 8. |
| 27708129 | Derived | Brys M, Fox MD, Agarwal S, Biagioni M, Dacpano G, Kumar P, Pirraglia E, Chen R, Wu A, Fernandez H, Wagle Shukla A, Lou JS, Gray Z, Simon DK, Di Rocco A, Pascual-Leone A. Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial. Neurology. 2016 Nov 1;87(18):1907-1915. doi: 10.1212/WNL.0000000000003279. Epub 2016 Oct 5. |
| BG001 | M1 Active rTMS + DLPFC Sham rTMS | High frequency stimulation of the primary motor cortex (M1) and sham stimulation of the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| BG002 | DLPFC Active rTMS + M1 Sham rTMS | High frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) and sham stimulation of the primary motor cortex (M1). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| BG003 | Double Sham rTMS | Sham rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | M1 Active rTMS + DLPFC Sham rTMS | High frequency stimulation of the primary motor cortex (M1) and sham stimulation of the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| OG002 | DLPFC Active rTMS + M1 Sham rTMS | High frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) and sham stimulation of the primary motor cortex (M1). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
| OG003 | Double Sham rTMS | Sham rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. |
|
|
| Primary | Hamilton Depression Scale (HAM-D) | To evaluate the depressive mood symptoms in PD. The HAM-D mean scores were reported for each group at each time point. The HAM-D Score Range is 0 - 56, where higher the score indicates greater severity of depressive mood symptoms. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
|
|
| Secondary | Clinical Anxiety Scale (CAS) | To evaluate anxiety in Parkinson's Disease. The CAS mean scores were reported for each group at each time point. The CAS Score Range is 0 - 100, where higher the score indicates greater severity of the anxiety symptoms. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
|
|
| Secondary | Apathy Evaluation Scale (AES) | To evaluate apathy in Parkinson's Disease. The AES mean scores were reported for each group at each time point. The AES Score Range is 0-42, where higher the score indicates greater severity of the apathy symptoms. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
|
|
| Secondary | Parkinson's Disease Questionnaire 39 (PDQ-39) | To assess the quality of life (QOL) in Parkinson's Disease. The PDQ-39 mean scores were reported for each group at each time point. The PDQ-39 Score Range is 0 - 156, where higher the score indicates greater impact on quality of life. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
|
|
| Secondary | Montreal Cognitive Assessment (MoCA) | To screen and follow cognitive function in Parkinson's Disease. The MoCA mean scores were reported for each group at each time point. The MoCA Score Range is 0 - 30, where 26-30 indicates normal cognition. | Posted | Mean | Standard Deviation | units on a scale | pre-treatment; 0,1,3, and 6 months post-treatment |
|
|
|
| Secondary | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I, II, and IV | To assess apathy, cognition, depression, activities of daily living (ADL), quality of life (QOL), and motor symptoms in Parkinson's Disease. The UPDRS I, II, IV total mean scores were reported for each group at each time point. The UPDRS I, II, IV scores were added together for each patient, with a total score range of 0 - 91, where higher the score indicates greater severity of the symptoms. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
|
|
| Secondary | Beck Depression Inventory (BDI-II) | To assess mood symptoms in Parkinson's Disease. The BDI-II mean scores were reported for each group at each time point. The BDI-II Score Range is 0 - 63, where higher the score indicates greater severity of the mood symptoms. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
|
|
| Secondary | Global Impression Scales | To assess symptom severity and treatment response in Parkinson's Disease. The CGI mean scores were reported for each group at each time point. The CGI Score Range is 1 - 8, where higher the score indicates greater severity of illness or worsening of illness. | Posted | Mean | Standard Deviation | units on a scale | Pre-treatment; Post-treatment 0,1,3, and 6 months. |
|
|
|
| Secondary | The Number All Types of Adverse Events. | To establish the safety and tolerability of rTMS in Parkinson's Disease. | Posted | Number | incidents of an adverse event | Baseline through Month 6 |
|
|
|
| 1 |
| 20 |
| 5 |
| 20 |
| EG001 | M1 Active rTMS + DLPFC Sham rTMS | High frequency stimulation of the primary motor cortex (M1) and sham stimulation of the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. | 1 | 14 | 3 | 14 |
| EG002 | DLPFC Active rTMS + M1 Sham rTMS | High frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) and sham stimulation of the primary motor cortex (M1). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. | 0 | 12 | 1 | 12 |
| EG003 | Double Sham rTMS | Sham rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS): DLPFC Active rTMS: Each treatment will consist of 2000 stimuli (50 X 4-second trains of 40 stimuli at 10 Hz, administered every 30 seconds for 25 minutes). Stimulus intensity for the first and second trains will be 80 and 90 percent of motor evoked potential (MEP), respectively. If no adverse effects are observed following each of the first two trains, then the subsequent trains will be given at MEP threshold. M1 Active rTMS: Stimulation will be applied one side at a time, to the motor cortex site at 90 percent of each subject's motor threshold intensity, and at a frequency of 10 Hz with 1000 stimuli per side (25 X 8-second trains of 40 stimuli). Sham rTMS: Patients from all four centers randomized to receive sham treatment will undergo the same procedures used in patients receiving active rTMS. | 1 | 15 | 0 | 15 |
| Choking Episode | Gastrointestinal disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Fall | Musculoskeletal and connective tissue disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Worsened Constipation | Gastrointestinal disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Hospitlization | General disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Atrial Fibrillation | Cardiac disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | 2 incidents determined to be unrelated to the study by overseeing physician. 2 incident determined to be possibly related to the study by overseeing physician. 1 incident determined to be related to the study by overseeing physician. |
|
| Heart Burn | Gastrointestinal disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Right-Sided Soreness | General disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Fall | Musculoskeletal and connective tissue disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Headache | Nervous system disorders | Determined to be possibly related to the study by overseeing physician. |
|
| Left Hip Ache | Musculoskeletal and connective tissue disorders | Determined to be possibly related to the study by overseeing physician. |
|
| Scalp Pain | Skin and subcutaneous tissue disorders | Determined to be related to the study by overseeing physician. |
|
| Left Shoulder Pain | Musculoskeletal and connective tissue disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Dizziness | Nervous system disorders | Determined to be unrelated to the study by overseeing physician. |
|
| Nausea | Gastrointestinal disorders | 1 incident determined to be unrelated to the study by overseeing physician; 2 incidents in same participant determined to be related to the study by overseeing physician. |
|
| Worsening Dyskinesia | Musculoskeletal and connective tissue disorders | Determined to be possibly related to the study by overseeing physician. |
|
| Torn Ligament of R Lower Extremity | Musculoskeletal and connective tissue disorders | Determined to be unrelated to the study by overseeing physician. |
|
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| Week 1 Post-Treatment |
|
| Month 1 Post-Treatment |
|
| Month 3 Post-Treatment |
|
| Month 6 Post-Treatment |
|
| Week 1 Post Treatment |
|
| Month 1 Post Treatment |
|
| Month 3 Post Treatment |
|
| Month 6 Post Treatment |
|
| Week 1 Post Treatment |
|
| Month 1 Post Treatment |
|
| Month 3 Post Treatment |
|
| Month 6 Post Treatment |
|
| Week 1 Post Treatment |
|
| Month 1 Post Treatment |
|
| Month 3 Post Treatment |
|
| Month 6 Post Treatment |
|
| Week 1 Post Treatment |
|
| Month 1 Post Treatment |
|
| Month 3 Post Treatment |
|
| Month 6 Post Treatment |
|
| Week 1 Post Treatment |
|
| Month 1 Post Treatment |
|
| Month 3 Post Treatment |
|
| Month 6 Post Treatment |
|
| Week 1 Post Treatment |
|
| Month 1 Post Treatment |
|
| Month 3 Post Treatment |
|
| Month 6 Post Treatment |
|
| Week 1 Post Treatment: Severity |
|
| Week 1 Post Treatment: Improvement |
|
| Month 1 Post Treatment: Severity |
|
| Month 1 Post Treatment: Improvement |
|
| Month 3 Post Treatment: Severity |
|
| Month 3 Post Treatment: Improvement |
|
| Month 6 Post Treatment: Severity |
|
| Month 6 Post Treatment: Improvement |
|