Parkinson DiseasePhase 1/2NCT00753519
Transcranial Magnetic Stimulation to Treat Parkinson's Disease
A Phase 1/2 study testing Real iTBS in people with Parkinson Disease, run by Mark Hallett at 1 site in United States.
Trial summary
This study will look at the effects of transcranial magnetic stimulation (TMS) on symptoms of Parkinson's disease. TMS is a method of brain stimulation that may be able to change the activity of the nerve cells of the brain. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Real iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Sep 2009
- Phase
- Phase 1/2
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 40 to 80 years with DOPA-responsive PD
- Hoehn and Yahr grade of 2 to 4 while off
- Must be on a regimen including levodopa.
- Total dose of levodopa and dopamine agonists (using dopamine equivalents) has to be equal to or more than 300 milligrams per day
- Problems with walking, including freezing gait time for a 10-meter distance greater than six seconds or more
Who cannot join
- Any active psychiatric disease or evidence of dementia
- History of seizures and epilepsy
- Concurrent use of tricyclic antidepressants, neuroleptic agents, or any other licit or illicit drugs other than anti-parkinsonian agents that could lower the seizure threshold except for SSRI
- Pallidotomy, implanted electrodes and generator for deep brain stimulation
- Pregnancy
- Surgically or traumatically implanted foreign bodies such as a pacemaker, implanted medical pump, implanted hearing aids, metal plate in the skull, or metal implant in the skull or eyes (other than dental appliances or fillings) that may pose a physical hazard during TEP.
Show all 11Show fewer
- Study would cause undue risk or stress for reasons such as tendency to fall, excessive fatigue, general frailty, or excessive apprehensiveness.
- Dementia as assessed by the Folstein's Mini-Mental Test Examination (MMSE less than or equal to 24/30) or mentally impaired patients having no capacity to provide their own consent (the physician establishing the diagnosis and applying UPDRS will evaluate patient's mental capacity using conventional clinical interview)
- Unable to walk a 10-meter distance.
- More than occasional falls, i.e. daily falls (corresponding to a score greater than or equal to 3 and more in UPDRS item 13), history of fall(s) with significant injuries, absence of postural response in the on condition and/or spontaneous loss of balance in the off condition (corresponding to a score of greater than or equal to 2 and greater than or equal to 3 in on/off condition, respectively, in UPDRS item 30)
- Pregnancy is unusual in patients with PD, grade 2-4. Urine sample for the pregnancy test will be obtained in patients of childbearing potential prior to the iTBS start, at the day of the initial interview and signing the consent form. Women of childbearing potential will be asked to take appropriate measures to prevent a pregnancy during the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Intermittent Theta-Burst Transcranial Magnetic Stimulation (TBS) for the Treatment of Parkinson Disease
This study will look at the effects of transcranial magnetic stimulation (TMS) on symptoms of Parkinson's disease. TMS is a method of brain stimulation that may be able to change the activity of the nerve cells of the brain. This study will examine the effects of a specific pattern of stimulation called intermittent theta-burst TMS (iTBS), which uses repeated magnetic pulses delivered in short bursts.
People with mild to moderately severe Parkinson's disease who are between 40 and 80 years of age and whose main problems are slow movement and stiffness may be eligible for this study.
Read more
Participants undergo the following tests and procedures:
- Random assignment to real or placebo (sham) iTBS treatment.
- iTBS sessions (real or sham) 4 times a week for 2 consecutive weeks. For this test, the subject sits in a comfortable chair. A wire coil is held on the subject's scalp, and a brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The subject hears a click and may feel a pulling sensation on the skin under the coil. There may be a twitch in the muscles of the face, arm or leg.
- Test of gait (walk), hand and arm movements before and after each session. The gait test requires walking 10 meters (about 30 yards) in the same corridor with the same shoes.
- Extended testing. The first and last gait tests (done before starting iTBS and after the eighth session) require coming off any Parkinson's medication for at least 12 hours before the test. On these test days, subjects also undergo a clinical examination, short neuropsychological test battery, a computer-based reaction time test and depression and quality-of-life rating scales. These procedures are repeated in a follow-up visit 1 month after the last session.
Read the detailed description
Objective
To demonstrate cumulative and long-lasting improvement of parkinsonian symptoms by iTBS and its safety in PD patients.
Study population
Patients (40-80 years of age) with PD, Hoehn and Yahr disease stage of 2 to 4 while off, being on a regimen including levodopa with a total dose of medication equal to more than 300 mg of levodopa, including their dopamine agonist agents, and having problems with walking and needing 6 seconds or more to walk a 10-meter distance.
Design
Randomized, double-blind, placebo (sham)-controlled study. Enrollment of 30 patients with PD in 2 groups (real versus sham stimulation). Performance (8 interventions) of iTBS with large circular coil over motor and prefrontal cortex on both sides. Assessment with standard tests of motor function over a one-month period.
Outcome measure
The primary endpoint is change in gait speed as assessed by the time it takes to walk 10 m.
Secondary endpoints include changes in bradykinesia as assessed by measuring the time it takes to do ten combined hand and arm movements, and in total and motor UPDRS score.
- Conditions
- Parkinson Disease
- Being tested
- Real iTBS, Sham iTBS
- Keywords
- Parkinson's Disease, Brain Stimulation, Motor Cortex, Bradykinesia, Parkinson Disease, PD
- Medical subject headings
- Parkinson Disease, Hypokinesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real iTBSDevice
Real iTBS was performed in 8 sessions over 2 successive weeks, a session/day for 4 consecutive days/week.
Sham iTBSDevice
Sham iTBS was performed in 8 sessions over 2 successive weeks, a session/day for 4 consecutive days/week.
| Study group | Role | What they receive |
|---|---|---|
| Real iTBS | Experimental | iTBS is a novel form of excitatory rTMS that may induce larger and longer lasting changes that standard rTMS. iTBS consists of bursts of 3 pulses at 50 Hz repeated at 200 msec intervals. The 2 sec trains were repeated 20 times every 10 sec. iTBS was applied to the primary motor and the dorsolateral prefrontal cortex bilaterally. Receives: Device: Real iTBS |
| Sham iTBS | Sham comparator | The sham coil was placed in the same areas, and made a similar sound as the rTMS but was without a magnetic pulse. Receives: Device: Sham iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gait Speed
Gait speed was assessed by measuring the time it takes to walk 10 meters. Subject's gait speed was measured while on medication and off medication for each group, i.e., real iTBS and sham iTBS. Two trials were averaged for each condition. Patients were instructed to walk fast without taking the risk of falling, wearing the same shoes and consistently using assistive devices if needed. Gait speed was measured at baseline, 1 day post intervention, and 1 month post intervention.
Measured: baseline, 1 day post iTBS
Secondary outcomes (3)
Bradykinesia
Bradykinesia refers to the slowness in executing a movement. Bradykinesia was assessed by measuring the time in seconds it takes to do the following sequence, 10 times: 1) hand closing and opening while squeezing a ball 2) elbow flexion 3) hand closing and opening, and 4) elbow extension. Subjects were allowed to practice these hand and arm movements until performance appeared not to get faster, and then were abstained from further practice to minimize learning effects. The time it takes subjects to execute the entire sequence 10 times with either the left or right arm/hand was measured. Means are reported for each group.
Measured: baseline, 1 day post iTBS
Total UPDRS Score
The Total Unified Parkinson's Disease Rating Scale (UPDRS) is an overall assessment scale that quantifies the signs and symptoms of Parkinson's disease. The total UPDRS score consists of mentation, behavior, mood, activities of daily living and motor components, and ranges from 0 (not affected) to 176 (most severely affected). The total UPDRS score is obtained from patient examination, interview and patient questionnaires.
Measured: baseline, 1 day post iTBS
Motor UPDRS
The Motor Unified Parkinson's Disease Rating Scale (UPDRS) includes only the motor assessment of the UPDRS (Part III) and examines speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability and body bradykinesia. The scores range from 0 (no motor impairment) to 108 (severe motor impairment).
Measured: baseline, 1 day post iTBS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2008 (estimated)
- Study startSep 2008
- Primary completionSep 2009
- Study completionSep 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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark Hallett
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor-investigator, Mark Hallett, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00753519
- Sponsor's protocol ID
- 080212
- Other IDs
- 08-N-0212
- Status last verified
- Oct 2012
- First submitted
- 13 Sep 2008
- Last updated
- 15 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Aarsland D, Larsen JP, Waage O, Langeveld JH. Maintenance electroconvulsive therapy for Parkinson's disease. Convuls Ther. 1997 Dec;13(4):274-7.
PubMed 9437571Baudewig J, Siebner HR, Bestmann S, Tergau F, Tings T, Paulus W, Frahm J. Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS). Neuroreport. 2001 Nov 16;12(16):3543-8. doi: 10.1097/00001756-200111160-00034.
PubMed 11733708Belmaker RH, Grisaru N. Magnetic stimulation of the brain in animal depression models responsive to ECS. J ECT. 1998 Sep;14(3):194-205.
PubMed 9773358
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intermittent Theta-Burst Transcranial Magnetic Stimulation (TBS) for the Treatment of Parkinson Disease
- ClinicalTrials.gov ID
- NCT00753519
- Acronym / sponsor ID
- 080212
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's Disease, Brain Stimulation, Motor Cortex, Bradykinesia, Parkinson Disease, PD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Mark HallettUS National Institutes of Health
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Sep 2008
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 16 Sep 2008 (estimated)
- Results
- Posted 15 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will look at the effects of transcranial magnetic stimulation (TMS) on symptoms of Parkinson's disease. TMS is a method of brain stimulation that may be able to change the activity of the nerve cells of the brain. This study will examine the effects of a specific pattern of stimulation called intermittent theta-burst TMS (iTBS), which uses repeated magnetic pulses delivered in short bursts.
People with mild to moderately severe Parkinson's disease who are between 40 and 80 years of age and whose main problems are slow movement and stiffness may be eligible for this study.
Participants undergo the following tests and procedures:
- Random assignment to real or placebo (sham) iTBS treatment.
- iTBS sessions (real or sham) 4 times a week for 2 consecutive weeks. For this test, the subject sits in a comfortable chair. A wire coil is held on the subject's scalp, and a brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The subject hears a click and may feel a pulling sensation on the skin under the coil. There may be a twitch in the muscles of the face, arm or leg.
- Test of gait (walk), hand and arm movements before and after each session. The gait test requires walking 10 meters (about 30 yards) in the same corridor with the same shoes.
- Extended testing. The first and last gait tests (done before starting iTBS and after the eighth session) require coming off any Parkinson's medication for at least 12 hours before the test. On these test days, subjects also undergo a clinical examination, short neuropsychological test battery, a computer-based reaction time test and depression and quality-of-life rating scales. These procedures are repeated in a follow-up visit 1 month after the last session.
Detailed description
Objective
To demonstrate cumulative and long-lasting improvement of parkinsonian symptoms by iTBS and its safety in PD patients.
Study population
Patients (40-80 years of age) with PD, Hoehn and Yahr disease stage of 2 to 4 while off, being on a regimen including levodopa with a total dose of medication equal to more than 300 mg of levodopa, including their dopamine agonist agents, and having problems with walking and needing 6 seconds or more to walk a 10-meter distance.
Design
Randomized, double-blind, placebo (sham)-controlled study. Enrollment of 30 patients with PD in 2 groups (real versus sham stimulation). Performance (8 interventions) of iTBS with large circular coil over motor and prefrontal cortex on both sides. Assessment with standard tests of motor function over a one-month period.
Outcome measure
The primary endpoint is change in gait speed as assessed by the time it takes to walk 10 m.
Secondary endpoints include changes in bradykinesia as assessed by measuring the time it takes to do ten combined hand and arm movements, and in total and motor UPDRS score.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Real iTBS | Experimental | Device: Real iTBSiTBS is a novel form of excitatory rTMS that may induce larger and longer lasting changes that standard rTMS. iTBS consists of bursts of 3 pulses at 50 Hz repeated at 200 msec intervals. The 2 sec trains were repeated 20 times every 10 sec. iTBS was applied to the primary motor and the dorsolateral prefrontal cortex bilaterally. |
| Sham iTBS | Sham comparator | Device: Sham iTBSThe sham coil was placed in the same areas, and made a similar sound as the rTMS but was without a magnetic pulse. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women aged 40 to 80 years with DOPA-responsive PD
- Hoehn and Yahr grade of 2 to 4 while off
- Must be on a regimen including levodopa.
- Total dose of levodopa and dopamine agonists (using dopamine equivalents) has to be equal to or more than 300 milligrams per day
- Problems with walking, including freezing gait time for a 10-meter distance greater than six seconds or more
Key exclusion criteria (11 listed)
- Any active psychiatric disease or evidence of dementia
- History of seizures and epilepsy
- Concurrent use of tricyclic antidepressants, neuroleptic agents, or any other licit or illicit drugs other than anti-parkinsonian agents that could lower the seizure threshold except for SSRI
- Pallidotomy, implanted electrodes and generator for deep brain stimulation
- 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 |
|---|---|---|
| Real iTBSReal iTBS was performed in 8 sessions over 2 successive weeks, a session/day for 4 consecutive days/week. | Device | Real iTBS |
| Sham iTBSSham iTBS was performed in 8 sessions over 2 successive weeks, a session/day for 4 consecutive days/week. | Device | Sham iTBS |
Primary outcome
Gait Speed
Time frame: baseline, 1 day post iTBS
Gait speed was assessed by measuring the time it takes to walk 10 meters. Subject's gait speed was measured while on medication and off medication for each group, i.e., real iTBS and sham iTBS. Two trials were averaged for each condition. Patients were instructed to walk fast without taking the risk of falling, wearing the same shoes and consistently using assistive devices if needed. Gait speed was measured at baseline, 1 day post intervention, and 1 month post intervention.
3 secondary outcomes
Bradykinesia
Time frame: baseline, 1 day post iTBS
Total UPDRS Score
Time frame: baseline, 1 day post iTBS
Motor UPDRS
Time frame: baseline, 1 day post iTBS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9437571Aarsland D, Larsen JP, Waage O, Langeveld JH. Maintenance electroconvulsive therapy for Parkinson's disease. Convuls Ther. 1997 Dec;13(4):274-7.
- Background: PubMed 11733708Baudewig J, Siebner HR, Bestmann S, Tergau F, Tings T, Paulus W, Frahm J. Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS). Neuroreport. 2001 Nov 16;12(16):3543-8. doi: 10.1097/00001756-200111160-00034.
- Background: PubMed 9773358Belmaker RH, Grisaru N. Magnetic stimulation of the brain in animal depression models responsive to ECS. J ECT. 1998 Sep;14(3):194-205.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Real iTBS in people with Parkinson Disease, run by Mark Hallett 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 5 inclusion and 11 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 15 Nov 2012. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Nov 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?
Gait Speed (time frame: baseline, 1 day post iTBS). 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 NCT00753519, which also lists 3 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 15 Nov 2012.