Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Apathy in Parkinson's Disease (ReStore)

This study has been completed.
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00955032
First received: August 5, 2009
Last updated: April 19, 2013
Last verified: September 2012
  Purpose

The purpose of this research study is to attempt to treat apathy in Parkinson's disease (PD) using high-frequency repetitive transcranial magnetic stimulation (rTMS) of the brain and to investigate the patterns of brain activation that may be involved in apathy. It is hypothesized that high-frequency rTMS of the left mid-dorsolateral frontal cortex will improve apathy in PD.


Condition Intervention
Parkinson's Disease
Device: High-Frequency Repetitive Transcranial Magnetic Stimulation
Device: Sham Repetitive Transcranial Magnetic Stimulation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Apathy in Parkinson's Disease.

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Apathy Evaluation Scale (AES) [ Time Frame: Pre-Tx; 10 days post tx ] [ Designated as safety issue: No ]
    The apathy evaluation scale is a 14-item self-report questionaire that provides a quantitative estimate of apathy symptoms. Items are given a score of 0-3, and a total score is summated using all items. Scores may range between 0 and 42. Higher scores are indicative of greater symptoms of apathy, and a score of 14 is suggestive of clinically significant symptoms.


Secondary Outcome Measures:
  • Lille Apathy Rating Scale (LARS) [ Time Frame: Pre-Tx; 10 days post-tx ] [ Designated as safety issue: No ]
    The Lille Apathy Rating Scale (LARS) is a 33-item interviewer administered structured questionaire designed to assess level of apathetic symptoms. The first 3 items are scored from -2 to +2, while the remainder items are scored from -1 to +1. Scores can range between -36 to +36. The more positive the score, the greater level of apathy symptoms.

  • Beck Depression Inventory-Second Edition (BDI-II) [ Time Frame: Pre-Tx; 10 days post-tx ] [ Designated as safety issue: No ]
    The Beck Depression Inventory-Second Edition (BDI-II) is a 21-item self-report questionaire that measures depressive symptoms. Each item is scored on a scale of 0-3, and items are summated to yield a total score. A higher score is indicative of greater symptoms of depression. Total scores may range between 0 and 63. A score greater than or equal of 14 is suggestive of clinically significant symptoms.

  • Hamilton Depression Rating Scale (HAM-D) [ Time Frame: Pre-Tx; 10 days post-tx ] [ Designated as safety issue: No ]
    The Hamilton Depression Rating Scale (HAM-D) is a 24-item interviewer administered structure questionaire designed to assess symptoms of depression. Items are scored with a range of 0-4, though 11 of the items are scored between 0 and 2. A total score is then calculated of all items which can range from 0 to 74. A higher score is indicative of more depressive symptoms, and a lower score post-tx is indicative of better outcome.


Enrollment: 24
Study Start Date: April 2007
Study Completion Date: December 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High-Frequency Repetitive Transcranial Magentic Stimulation
High-Frequency repetitive transcranial magnetic stimulation patients randomized to this treatment will receive left prefrontal rTMS, each treatment will consist of 2000 stimuli (50 - 8-second trains of 40 stimuli at 5 Hz). We will administer rTMS trains every 30 seconds for 25 minutes. Stimulus intensity for the first and second trains will be 80 and 90% of Motor Evoked Potential (MEP) threshold, respectively.
Device: High-Frequency Repetitive Transcranial Magnetic Stimulation
In patients randomized to receive left prefrontal rTMS, each treatment will consist of 2000 stimuli (50 - 8-second trains of 40 stimuli at 5 Hz). We will administer rTMS trains every 30 seconds for 25 minutes. Stimulus intensity for the first and second trains will be 80 and 90% of MEP threshold, respectively.
Other Name: rTMS Treatment
Sham Comparator: Sham Repetitive Transcranial Magentic Stimulation
Sham repetitive transcranial magnetic stimulation patients randomized to receive the sham rTMS will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using Magstim Placebo 70 mm figure-of-8 shaped coils which produce discharge noise and vibration similar to a real 70 mm coil without stimulating the cerebral cortex. However, in addition to obvious coil discharge noise, rTMS also causes electrical stimulation of the scalp. We will simulate this experience by attaching surface electrodes underneath the sham coil and in contact with the scalp.
Device: Sham Repetitive Transcranial Magnetic Stimulation
Patients randomized to receive sham rTMS will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using Magstim Placebo 70 mm figure-of-8 shaped coils which produce discharge noise and vibration similar to a real 70 mm coil without stimulating the cerebral cortex. However, in addition to obvious coil discharge noise, rTMS also causes electrical stimulation of the scalp. We will simulate this experience by attaching surface electrodes underneath the sham coil and in contact with the scalp.
Other Name: Sham Treatment

Detailed Description:

Apathy is a syndrome characterized by a primary lack of motivation and it manifests in three domains: behavioral (lack of effort and productivity, dependence on others for structuring daily activities), cognitive (loss of interest in new experiences, lack of concern for one's problems) and affective (flattened affect and lack of response to positive or negative events). Apathy has been consistently attributed to functional disturbance of neural systems involving mesial frontal and the anterior cingulate cortex (ACC), an area with reciprocal connections with limbic, frontal cortices and the basal ganglia.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool used to manipulate activity in specific brain neural circuits through the skull and, in turn, induce short-term (milliseconds) and long-term (minutes to hours) changes in behavior. The duration of effect depends on the stimulation mode. Several studies have now demonstrated that rTMS may facilitate or modulate behavior beyond the actual stimulation. rTMS of the mid-dorsolateral frontal cortex (MDLFC) has been used to treat depression presumably because of its modulatory effect on the fronto-cingulate system (MDLFC and the ACC circuitry). Studies have shown that rTMS of the left MDLFC modulates the blood flow response in the ACC. We therefore hypothesize that high-frequency rTMS of the left MDLFC will also improve apathy in PD.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. diagnosis of "probable" PD, defined by the presence of at least 2 out of 3 cardinal motor features of PD (resting tremor, rigidity, and bradykinesia, plus a sustained and significant response to dopaminergic treatment);
  2. age 30 or over; and
  3. on stable medications for at least 30 days.

Exclusion Criteria:

  1. features suggestive of other causes of parkinsonism/ parkinson-plus syndromes;
  2. history of deep brain stimulation or ablation surgery, significant headaches, epilepsy or seizure disorder, mass brain lesions, or major head trauma leading to loss of consciousness of any length;
  3. family (1st degree relatives) history of epilepsy;
  4. evidence for dementia;
  5. presence of contraindications for functional magnetic resonance imaging (fMRI);
  6. history of schizophrenia, schizoaffective disorder, other psychosis, rapid-cycling bipolar illness, alcohol/drug abuse within the past year;
  7. need for rapid clinical response due to conditions such as initiation, psychosis, or suicidality;
  8. unstable medical condition such as diabetes, cardiac disease, hypertension;
  9. pregnancy; and
  10. colorblindness.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00955032

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32611
Sponsors and Collaborators
University of Florida
Michael J. Fox Foundation for Parkinson's Research
Investigators
Principal Investigator: Hubert H Fernandez, M.D. University of Florida
  More Information

Additional Information:
No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00955032     History of Changes
Other Study ID Numbers: 0004762006
Study First Received: August 5, 2009
Results First Received: December 5, 2011
Last Updated: April 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
Parkinson's disease
Apathy
rTMS
Repetitive transcranial magnetic stimulation
Depression

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders

ClinicalTrials.gov processed this record on November 25, 2014