rTMS for Motor and Mood Symptoms of Parkinson's Disease

NCT01080794 | Completed Results DMC

• 1 other identifier: 2010P000002
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 6

Brief 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).

Conditions

Parkinson's Disease; Depression

Keywords

Parkinson's Disease; Depression; Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (2)

• 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.

Secondary Outcomes (8)

• Clinical Anxiety Scale (CAS)

  Pre-treatment; Post-treatment 0,1,3, and 6 months.

• Apathy Evaluation Scale (AES)

  Pre-treatment; Post-treatment 0,1,3, and 6 months.

• Parkinson's Disease Questionnaire 39 (PDQ-39)

  Pre-treatment; Post-treatment 0,1,3, and 6 months.

• Montreal Cognitive Assessment (MoCA)

  pre-treatment; 0,1,3, and 6 months post-treatment

• Unified Parkinson's Disease Rating Scale (UPDRS) Parts I, II, and IV

  Pre-treatment; Post-treatment 0,1,3, and 6 months.

Study Arms (4)

Double rTMS

ACTIVE COMPARATOR

High frequency rTMS stimulation of the bilateral primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC).

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).

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).

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).

Device: Repetitive transcranial magnetic stimulation (rTMS)

Interventions

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.

Also known as: Transcranial Magnetic Stimulation, Noninvasive Brain Stimulation, Magstim Corporation

DLPFC Active rTMS + M1 Sham rTMS; Double Sham rTMS; Double rTMS; M1 Active rTMS + DLPFC Sham rTMS

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• University of California, Los Angeles: collaborator
• University of Florida: collaborator
• University Health Network, Toronto: collaborator
• The Cleveland Clinic: collaborator
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (6)

University of California Los Angeles

Los Angeles, California, United States

Location

University of Florida

Gainesville, Florida, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

The Cleveland Clinic

Cleveland, Ohio, United States

Location

Oregon Health and Science University

Portland, Oregon, United States

Location

University Health Network

Toronto, Ontario, Canada

Location

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MeSH Terms

Conditions

Parkinson Disease; Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Alvaro Pascual-Leone
• Organization: Beth Israel Deaconess Medical Center

apleone@bidmc.harvard.edu

(617) 667-0203

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: March 3, 2010
• First Posted: March 4, 2010
• Study Start: May 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 13, 2017
• Results First Posted: April 13, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); CA (1)