Parkinson's DiseaseReStoreNCT00955032
Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Apathy in Parkinson's Disease
A study testing High-Frequency Repetitive Transcranial Magnetic Stimulation in people with Parkinson's Disease, run by University of Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- High-Frequency Repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Dec 2009
- 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 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
- age 30 or over; and
- on stable medications for at least 30 days.
Who cannot join
- features suggestive of other causes of parkinsonism/ parkinson-plus syndromes;
- 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;
- family (1st degree relatives) history of epilepsy;
- evidence for dementia;
- presence of contraindications for functional magnetic resonance imaging (fMRI);
- history of schizophrenia, schizoaffective disorder, other psychosis, rapid-cycling bipolar illness, alcohol/drug abuse within the past year;
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- need for rapid clinical response due to conditions such as initiation, psychosis, or suicidality;
- unstable medical condition such as diabetes, cardiac disease, hypertension;
- pregnancy; and
- colorblindness.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Apathy in Parkinson's Disease.
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.
Read the 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
- Being tested
- High-Frequency Repetitive Transcranial Magnetic Stimulation, Sham Repetitive Transcranial Magnetic Stimulation
- Keywords
- Parkinson's disease, Apathy, rTMS, Repetitive transcranial magnetic stimulation, Depression
- Medical subject headings
- Parkinson Disease, Lethargy, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-Frequency Repetitive Transcranial Magnetic StimulationDevice
Also called rTMS Treatment
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 Magnetic StimulationDevice
Also called Sham Treatment
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.
| Study group | Role | What they receive |
|---|---|---|
| High-Frequency Repetitive Transcranial Magentic Stimulation | Experimental | 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. Receives: Device: High-Frequency Repetitive Transcranial Magnetic Stimulation |
| Sham Repetitive Transcranial Magentic Stimulation | Sham comparator | 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. Receives: Device: Sham Repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apathy Evaluation Scale (AES)
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.
Measured: Pre-Tx; 10 days post tx
Secondary outcomes (3)
Lille Apathy Rating Scale (LARS)
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.
Measured: Pre-Tx; 10 days post-tx
Beck Depression Inventory-Second Edition (BDI-II)
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.
Measured: Pre-Tx; 10 days post-tx
Hamilton Depression Rating Scale (HAM-D)
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.
Measured: Pre-Tx; 10 days post-tx
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2009 (estimated)
- Study startApr 2007
- Primary completionOct 2009
- Study completionDec 2009
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.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Sponsor
- Investigators
- Hubert H Fernandez, M.D., Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00955032
- Sponsor's protocol ID
- 0004762006
- Acronym
- ReStore
- Status last verified
- Sep 2012
- First submitted
- 5 Aug 2009
- Last updated
- 26 Apr 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Apathy in Parkinson's Disease.
- ClinicalTrials.gov ID
- NCT00955032
- Acronym / sponsor ID
- ReStore / 0004762006
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, Apathy, rTMS, Repetitive transcranial magnetic stimulation, Depression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- Apr 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 7 Aug 2009 (estimated)
- Results
- Posted 20 Feb 2012
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-Frequency Repetitive Transcranial Magentic Stimulation | Experimental | Device: High-Frequency Repetitive Transcranial Magnetic StimulationHigh-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. |
| Sham Repetitive Transcranial Magentic Stimulation | Sham comparator | Device: Sham Repetitive Transcranial Magnetic StimulationSham 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. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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);
- age 30 or over; and
- on stable medications for at least 30 days.
Key exclusion criteria (10 listed)
- features suggestive of other causes of parkinsonism/ parkinson-plus syndromes;
- 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;
- family (1st degree relatives) history of epilepsy;
- evidence for dementia;
- presence of contraindications for functional magnetic resonance imaging (fMRI);
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 |
|---|---|---|
| High-Frequency Repetitive Transcranial Magnetic StimulationAlso: rTMS TreatmentIn 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. | Device | High-Frequency Repetitive Transcranial Magentic Stimulation |
| Sham Repetitive Transcranial Magnetic StimulationAlso: Sham TreatmentPatients 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. | Device | Sham Repetitive Transcranial Magentic Stimulation |
Primary outcome
Apathy Evaluation Scale (AES)
Time frame: Pre-Tx; 10 days post tx
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.
3 secondary outcomes
Lille Apathy Rating Scale (LARS)
Time frame: Pre-Tx; 10 days post-tx
Beck Depression Inventory-Second Edition (BDI-II)
Time frame: Pre-Tx; 10 days post-tx
Hamilton Depression Rating Scale (HAM-D)
Time frame: Pre-Tx; 10 days post-tx
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Movement Disorders Center at the University of FloridaLink provided by the sponsor.
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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.
Hubert H Fernandez, M.D. principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-Frequency Repetitive Transcranial Magnetic Stimulation in people with Parkinson's Disease, run by University of Florida at 1 site in United States.
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 3 inclusion and 10 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 26 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 20 Feb 2012). 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?
Apathy Evaluation Scale (AES) (time frame: Pre-Tx; 10 days post tx). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Apr 2013.