Parkinson's DiseaseMASTER-PDNCT01080794
rTMS for Motor and Mood Symptoms of Parkinson's Disease
A study testing Repetitive transcranial magnetic stimulation (rTMS) in people with Parkinson's Disease and Depression, run by Beth Israel Deaconess Medical Center at 6 sites in 2 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Parkinson's Disease, Depression
- What is being tested?
- Repetitive transcranial magnetic stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 6 sitesin 2 countries
- Study dates
- May 2010to Jun 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of PD according to the UK Brain Bank Criteria, confirmed by a neurologist with expertise in movement disorders.
- Minimum of 3 years since the formal diagnosis of PD, and requiring dopaminergic therapy (at a minimum, on levodopa and/or dopamine agonist therapy).
- Minimum baseline OFF score on the motor UPDRS of 15 points of more.
- Lack of features suggestive of atypical parkinsonism, such as early prominent cerebellar, pyramidal, or autonomic dysfunction; supranuclear gaze palsy; falls within the first year of symptoms; hallucinations prior to initiating a dopaminergic agent.
- No history of neuroleptics or other drugs that induce parkinsonism in the past 60 days.
- Currently optimally treated with medications and, in the view of the treating neurologist, will unlikely be requiring anti-PD medication adjustments in the next 6 months.
Show all 12Show fewer
- On a stable dose of all medications for 30 days (except anti-depressants- which should be stable for at least 90 days).
- Lack of dementia such that, in the view of the enrolling investigator, the patient is able to give proper informed consent. In addition, all patients must score at least a 26 out of 30 on the screening MMSE.
- HAM-D score > 12 on the first 17 questions of the scale, despite the current use of antidepressant(s) for at least 90 days, or documentation of adequate trial of antidepressants (i.e. at least 6 weeks on an optimal dose), or documentation of intolerability to antidepressants.
- Untreated depression or on a stable dose of antidepressants for 90 days (untreated patients need to have tried at least one antidepressant in the past).
- Age 21 years or older.
- Patient meets the criteria for a depressive disorder based on either the MINI interview (major depression) or SCID (minor depression, or dysthymia).
Who cannot join
- Intracranial metallic bodies (e.g. from prior neurosurgical procedure).
- Signs or symptoms of increased intracranial pressure.
- Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit or ventriculoperitoneal shunt.
- History of seizures or unexplained loss of consciousness.
- Possible pregnancy.
- Family history of medication refractory epilepsy.
Show all 20Show fewer
- History of substance abuse within the last 6 months.
- History of known structural brain abnormality.
- History of exposure to repetitive TMS in the past (to minimizing risk of unblinding sham condition).
- History of exposure to ECT in the past.
- Patients with suicidal ideation deemed by the investigator to be significant enough to render the individual a suicidal risk.
- Patients with a history of hospitalization for suicidal ideation/attempts.
- Patients requiring hospitalization for their depression within the past six months will not be allowed in the study. If a participating subject's depression worsens during the study to a degree that hospitalization is deemed necessary, or if the subject develops significant suicidal ideation, he/she will be withdrawn from the study and referred to a psychiatrist for treatment.
- Patients with bipolar affective disorder and those whose depression is characterized by psychotic features.
- Patients with a history of spontaneous hallucinations or delusions as well as those with other underlying psychotic disorders (e.g., schizophrenia, schizoaffective disorder, delusional disorder). The presence of visual illusions or hallucinations deemed by the enrolling physician to be clearly related to antiparkinsonian medications will be allowed but only if the enrolling physician believes that they are stable and unlikely to require changes in medication (i.e., addition of an antipsychotic or reduction in antiparkinsonian drug dosage). Patients with delusions will be excluded.
- Subjects judged by the clinician investigator to have dementia (by DSM-IV and MMSE criteria) will be excluded.
- Subjects judged by the clinician investigator to have dementia (by MoCA criteria) will be excluded.
- Subjects with unstable medical condition such as diabetes, cardiac disease, and hypertension.
- Subjects with brittle or severe motor fluctuation that will cause severe discomfort during OFF medication testing at Baseline, immediately post-TMS, and at Months 1, 3, and 6.
- Excessive alcohol use or taking one of the following exclusionary medications: Imipramine, Amitriptyline, Doxepin, Nortriptyline, Maprotiline, Chlorpromazine, Clozapine, Foscarnet, Ganciclovir, Ritonavir, Amphetamines (MDMA, ecstasy), cocaine, phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), theophylline, and haloperidol.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
The Cleveland Clinic
Cleveland, Ohio
University of Florida
Gainesville, Florida
University of California Los Angeles
Los Angeles, California
Oregon Health and Science University
Portland, Oregon
About this study
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) for Motor and Mood Symptoms of Parkinson's Disease (MASTER-PD), a Multicenter Clinical Trial
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).
Read the detailed description
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.
- Conditions
- Parkinson's Disease, Depression
- Being tested
- Repetitive transcranial magnetic stimulation (rTMS)
- Keywords
- Parkinson's Disease, Depression, Transcranial Magnetic Stimulation
- Medical subject headings
- Parkinson Disease, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive transcranial magnetic stimulation (rTMS)Device
Also called Transcranial Magnetic Stimulation, Noninvasive Brain Stimulation, Magstim Corporation
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.
| Study group | Role | What they receive |
|---|---|---|
| Double rTMS | Active comparator | High frequency rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Receives: Device: Repetitive transcranial magnetic stimulation (rTMS) |
| 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). Receives: Device: Repetitive transcranial magnetic stimulation (rTMS) |
| 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). Receives: Device: Repetitive transcranial magnetic stimulation (rTMS) |
| Double Sham rTMS | Sham comparator | Sham rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). Receives: Device: Repetitive transcranial magnetic stimulation (rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Pre-treatment; Post-treatment 0,1,3, and 6 months.
Secondary outcomes (8)
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.
Measured: Pre-treatment; Post-treatment 0,1,3, and 6 months.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline through Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2010 (estimated)
- Study startMay 2010
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (92)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles, University of Florida, University Health Network, Toronto, The Cleveland Clinic, Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Principal investigator, Alvaro Pascual-Leone, Beth Israel Deaconess Medical Center
- Investigators
- Alvaro Pascual-Leone, M.D., Ph.D., Principal investigator, Beth Israel Deaconess Medical CenterAllan Wu, M.D., Principal investigator, University of California, Los AngelesHubert Fernandez, M.D., Principal investigator, The Cleveland ClinicRobert Chen, BChir, MA, MB, MSc, Principal investigator, University Health Network, TorontoAparna Wagle-Shukla, MD, Principal investigator, University of FloridaJau-Shin Lou, MD, PhD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01080794
- Sponsor's protocol ID
- 2010P000002
- Acronym
- MASTER-PD
- Status last verified
- Mar 2017
- First submitted
- 3 Mar 2010
- Last updated
- 13 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Adler CH. Nonmotor complications in Parkinson's disease. Mov Disord. 2005;20 Suppl 11:S23-9. doi: 10.1002/mds.20460.
PubMed 15822106BECK 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.
PubMed 13688369Benabid 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.
PubMed 16280671Bornke 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.
PubMed 15354390Brusa 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.
PubMed 16887383Buhmann 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.
PubMed 15509619Burn 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.
PubMed 15312281Burt 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.
PubMed 12057034Cantello R. Applications of transcranial magnetic stimulation in movement disorders. J Clin Neurophysiol. 2002 Aug;19(4):272-93. doi: 10.1097/00004691-200208000-00003.
PubMed 12436085Cardoso 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.
PubMed 17708780Chaudhuri 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.
PubMed 16488379Conca 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.
PubMed 9121622Crow 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.
PubMed 2871792Aarsland 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.
PubMed 12197850del 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.
PubMed 17097342
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Transcranial Magnetic Stimulation (rTMS) for Motor and Mood Symptoms of Parkinson's Disease (MASTER-PD), a Multicenter Clinical Trial
- ClinicalTrials.gov ID
- NCT01080794
- Acronym / sponsor ID
- MASTER-PD / 2010P000002
- Conditions
- Parkinson's Disease, Depression
- Keywords
- Parkinson's Disease, Depression, Transcranial Magnetic Stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- University of California, Los Angeles, University of Florida, University Health Network, Toronto, The Cleveland Clinic, Michael J. Fox Foundation for Parkinson's Research
- Study start
- May 2010
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 4 Mar 2010 (estimated)
- Results
- Posted 13 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Double rTMS | Active comparator | Device: Repetitive transcranial magnetic stimulation (rTMS)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 | Device: Repetitive transcranial magnetic stimulation (rTMS)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 | Device: Repetitive transcranial magnetic stimulation (rTMS)High frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) and sham stimulation of the primary motor cortex (M1). |
| Double Sham rTMS | Sham comparator | Device: Repetitive transcranial magnetic stimulation (rTMS)Sham rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC). |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Diagnosis of PD according to the UK Brain Bank Criteria, confirmed by a neurologist with expertise in movement disorders.
- Minimum of 3 years since the formal diagnosis of PD, and requiring dopaminergic therapy (at a minimum, on levodopa and/or dopamine agonist therapy).
- Minimum baseline OFF score on the motor UPDRS of 15 points of more.
- Lack of features suggestive of atypical parkinsonism, such as early prominent cerebellar, pyramidal, or autonomic dysfunction; supranuclear gaze palsy; falls within the first year of symptoms; hallucinations prior to initiating a dopaminergic agent.
- No history of neuroleptics or other drugs that induce parkinsonism in the past 60 days.
Key exclusion criteria (20 listed)
- Intracranial metallic bodies (e.g. from prior neurosurgical procedure).
- Signs or symptoms of increased intracranial pressure.
- Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit or ventriculoperitoneal shunt.
- History of seizures or unexplained loss of consciousness.
- Possible pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive transcranial magnetic stimulation (rTMS)Also: Transcranial Magnetic Stimulation, Noninvasive Brain Stimulation, Magstim CorporationDLPFC 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. | Device | DLPFC Active rTMS + M1 Sham rTMS, Double Sham rTMS, Double rTMS, M1 Active rTMS + DLPFC Sham rTMS |
Primary outcome
Motor Subscale of the Unified Parkinson's Disease Rating Scale (UPDRS Part III)
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
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.
Hamilton Depression Scale (HAM-D)
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
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.
8 secondary outcomes
Clinical Anxiety Scale (CAS)
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
Apathy Evaluation Scale (AES)
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
Parkinson's Disease Questionnaire 39 (PDQ-39)
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
Montreal Cognitive Assessment (MoCA)
Time frame: pre-treatment; 0,1,3, and 6 months post-treatment
Unified Parkinson's Disease Rating Scale (UPDRS) Parts I, II, and IV
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
Beck Depression Inventory (BDI-II)
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
Global Impression Scales
Time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.
The Number All Types of Adverse Events.
Time frame: Baseline through Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15822106Adler CH. Nonmotor complications in Parkinson's disease. Mov Disord. 2005;20 Suppl 11:S23-9. doi: 10.1002/mds.20460.
- Background: PubMed 13688369BECK 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.
- Background: PubMed 16280671Benabid 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.
- Background: PubMed 15354390Bornke 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.
- Background: PubMed 16887383Brusa 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.
- Background: PubMed 15509619Buhmann 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.
- Background: PubMed 15312281Burn 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.
- Background: PubMed 12057034Burt 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.
- Background: PubMed 12436085Cantello R. Applications of transcranial magnetic stimulation in movement disorders. J Clin Neurophysiol. 2002 Aug;19(4):272-93. doi: 10.1097/00004691-200208000-00003.
- Background: PubMed 17708780Cardoso 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.
- Background: PubMed 16488379Chaudhuri 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.
- Background: PubMed 9121622Conca 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alvaro Pascual-Leone, M.D., Ph.D. principal investigator
Beth Israel Deaconess Medical Center
Allan Wu, M.D. principal investigator
University of California, Los Angeles
Hubert Fernandez, M.D. principal investigator
The Cleveland Clinic
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive transcranial magnetic stimulation (rTMS) in people with Parkinson's Disease and Depression, run by Beth Israel Deaconess Medical Center at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motor Subscale of the Unified Parkinson's Disease Rating Scale (UPDRS Part III) (time frame: Pre-treatment; Post-treatment 0,1,3, and 6 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01080794, which also lists 92 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2017.