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

NCT ID: NCT00955032

Last Updated: 2013-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2009-12-31

Brief Summary

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.

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

High-Frequency Repetitive Transcranial Magnetic Stimulation

Intervention Type: DEVICE

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.

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.

Group Type: SHAM_COMPARATOR

Sham Repetitive Transcranial Magnetic Stimulation

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DEVICE

Other Intervention Names

rTMS Treatment; Sham Treatment

Eligibility 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.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hubert H Fernandez, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Related Links

http://mdc.mbi.ufl.edu/

Movement Disorders Center at the University of Florida

Other Identifiers

0004762006

Identifier Type: -

Identifier Source: org_study_id