Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
We hypothesize that reductions in gamma activity are a key mechanism underlying cognitive dysfunction in PD and that interventions to increase gamma activity will improve cognition.
Parkinson's disease (PD) is the second most common neurodegenerative illness (after Alzheimer's disease) affecting 1-2% of people over age 65.3 Although PD is traditionally characterized by its motor symptoms (e.g. tremor, stiffness, slowness), research demonstrates that cognitive dysfunction has a greater impact on patient suffering and caregiver burden despite being under-recognized. Cognitive dysfunction is a significant risk factor for psychosis, dementia, nursing home placement and affects 20- 40% of PD patients even at the time of initial diagnosis.4,5 In patients with PD surviving 20 years or longer, cognitive dysfunction is the leading cause of nursing home placement and three fourths of PD patients ultimately develop dementia.6
We know that neurons in the brain communicate with each other by firing at certain frequencies. A growing literature shows that high frequency (30-50 Hz) brain activity called gamma activity is particularly important for communication between distant brain areas and is critical to normal cognition.7 Prior studies also show that gamma activity is reduced in PD.8 However, we do not know why gamma activity is reduced in PD or the relationship between changes in gamma activity and cognitive dysfunction. We hypothesize that reductions in gamma activity are a key mechanism underlying cognitive dysfunction in PD and that interventions to increase gamma activity will improve cognition.
To test this hypothesis we propose to use a novel combination of research methods including magnetoencephalography (MEG) and repetitive transcranial magnetic stimulation (rTMS). MEG measures magnetic activity over the scalp to determine brain activity. We will use MEG to determine whether reductions in gamma activity are related to cognitive dysfunction in PD. TMS uses a magnetic coil placed over the scalp to stimulate brain activity. While there is evidence that repetitive TMS (transcranial magnetic stimulation) increases gamma activity and may improve cognition, it has not been studied for this purpose in PD. We will apply repetitive TMS to PD patients to determine whether gamma activity and/or cognitive function may be improved non-invasively.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Parkinson's Disease Subjects, (rTMS) | Experimental | The PD subjects will be randomized, and on a separate day receive a course of either real (rTMS) or sham TMS. Twenty minutes after this treatment subjects will again perform the same working memory task (at 9am to control for fatigue and diurnal effects) while having MEG data recorded |
|
| Control Subjects (rTMS) | Experimental | The control subjects will be randomized, and on a separate day receive a course of either real (rTMS) or sham TMS. Twenty minutes after this treatment subjects will again perform the same working memory task (at 9am to control for fatigue and diurnal effects) while having MEG data recorded |
|
| Parkinson's Disease Subjects, (sTMS) | Sham Comparator | The PD subjects will be randomized, and on a separate day receive a course of either real (rTMS) or sham TMS. Twenty minutes after this treatment subjects will again perform the same working memory task (at 9am to control for fatigue and diurnal effects) while having MEG data recorded |
|
| Control Subjects (sTMS) | Sham Comparator | The control subjects will be randomized, and on a separate day receive a course of either real (rTMS) or sham TMS. Twenty minutes after this treatment subjects will again perform the same working memory task (at 9am to control for fatigue and diurnal effects) while having MEG data recorded |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rTMS | Device | TMS: Repetitive TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Stimulator (Magstim, Jali Medical US distributors, Woburn, MA). Repetitive pulses will be delivered to the right and left pre-frontal cortex (Brodman area 46) using a frameless stereotactic navigation system and the subject's MRI in Brainsight software. Stimuli will be delivered at 20 Hz at 90% of the subjects resting motor threshold (rMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. The same TMS parameters as active stimulation but with the coil held at 90° to the scalp to induce similar somatic sensations and noise as in the active group with minimal direct brain effects. |
| Measure | Description | Time Frame |
|---|---|---|
| Differences in Error Rates on the NBack Task Between Real and Sham Stimulation Trials | The primary cognitive outcome will be the error rates on the N-back task measured before and after real or sham TMS as a measure of working memory. A negative number indicates that error rate was higher (working memory skills were worse) in the sham than the real condition. A positive number indicates lower error rates (better working memory skills) in the sham vs real stimulation. | Change immediately after a single session TMS (pre will be done 1 week prior) |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Benzi Kluger, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Denver Building 534 | Aurora | Colorado | 80045 | United States |
In Progress
Not provided
Not provided
Not provided
Not provided
PI withdrawal of subjects during MEG screening:
Several participants have ferromagnetic compounds on their body, that they cannot remove (dental work, pins or screws in bones...) but cause artifacts in the data, which prevents proper data analysis. Participants are quickly screened for artifacts during their baseline visit and possibly withdrawn.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Parkinson's Disease Subjects | Participants performed a working memory task during MEG recording. Then PD subjects were randomized to receive a course of either real (rTMS) or sham TMS on a separate day (max 1 week after first MEG). 20 min after TMS subjects again performed the same working memory task while having MEG data recorded REAL: Repetitive TMS was delivered at 20 Hz at 90% of the subjects resting motor threshold (RMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. SHAM: stimulation was delivered with the same TMS parameters as active simulation but the coil held at 90 degree to the scalp to induce similar somatic sensations and noise as in the active group with minimal brain effects. |
| FG001 | Control Subjects | Participants performed a working memory task during MEG recording. Then control subjects were randomized to receive a course of either real (rTMS) or sham TMS on a separate day (max 1 week after first MEG). 20 min after TMS subjects again performed the same working memory task while having MEG data recorded. REAL: Repetitive TMS was delivered at 20 Hz at 90% of the subjects resting motor threshold (RMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. SHAM: stimulation was delivered with the same TMS parameters as active simulation but the coil held at 90 degree to the scalp to induce similar somatic sensations and noise as in the active group with minimal brain effects. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Parkinson's Disease Subjects | Participants performed a working memory task during MEG recording. Then PD subjects were randomized to receive a course of either real (rTMS) or sham TMS on a separate day (max 1 week after first MEG). 20 min after TMS subjects again performed the same working memory task while having MEG data recorded REAL: Repetitive TMS was delivered at 20 Hz at 90% of the subjects resting motor threshold (RMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. SHAM: stimulation was delivered with the same TMS parameters as active simulation but the coil held at 90 degree to the scalp to induce similar somatic sensations and noise as in the active group with minimal brain effects. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Differences in Error Rates on the NBack Task Between Real and Sham Stimulation Trials | The primary cognitive outcome will be the error rates on the N-back task measured before and after real or sham TMS as a measure of working memory. A negative number indicates that error rate was higher (working memory skills were worse) in the sham than the real condition. A positive number indicates lower error rates (better working memory skills) in the sham vs real stimulation. | Posted | Mean | Standard Deviation | incorrect responses | Change immediately after a single session TMS (pre will be done 1 week prior) |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Parkinson's Disease Subjects | Participants performed a working memory task during MEG recording. Then PD subjects were randomized to receive a course of either real (rTMS) or sham TMS on a separate day (max 1 week after first MEG). 20 min after TMS subjects again performed the same working memory task while having MEG data recorded REAL: Repetitive TMS was delivered at 20 Hz at 90% of the subjects resting motor threshold (RMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. SHAM: stimulation was delivered with the same TMS parameters as active simulation but the coil held at 90 degree to the scalp to induce similar somatic sensations and noise as in the active group with minimal brain effects. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | Nervous system disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Isabelle Buard, PhD | University of Colorado Denver | (303)472-5973 | Isabelle.Buard@cuanschutz.edu |
Not provided
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Sham TMS | Device | Sham TMS will be administered with a Magstim sham coil with electrodes attached to mimic the sounds and sensation of real TMS. The site and frequency of stimulation will be identical to the real TMS described above. |
|
| BG001 | Control Subjects | Participants performed a working memory task during MEG recording. Then control subjects were randomized to receive a course of either real (rTMS) or sham TMS on a separate day (max 1 week after first MEG). 20 min after TMS subjects again performed the same working memory task while having MEG data recorded REAL: Repetitive TMS was delivered at 20 Hz at 90% of the subjects resting motor threshold (RMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. SHAM: stimulation was delivered with the same TMS parameters as active simulation but the coil held at 90 degree to the scalp to induce similar somatic sensations and noise as in the active group with minimal brain effects. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Control Subjects | Participants performed a working memory task during MEG recording. Then control subjects were randomized to receive a course of either real (rTMS) or sham TMS on a separate day (max 1 week after first MEG). 20 min after TMS subjects again performed the same working memory task while having MEG data recorded REAL: Repetitive TMS was delivered at 20 Hz at 90% of the subjects resting motor threshold (RMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. SHAM: stimulation was delivered with the same TMS parameters as active simulation but the coil held at 90 degree to the scalp to induce similar somatic sensations and noise as in the active group with minimal brain effects. |
|
|
| 0 |
| 36 |
| 0 |
| 36 |
| 1 |
| 36 |
| EG001 | Control Subjects | Participants performed a working memory task during MEG recording. Then control subjects were randomized to receive a course of either real (rTMS) or sham TMS on a separate day (max 1 week after first MEG). 20 min after TMS subjects again performed the same working memory task while having MEG data recorded. REAL: Repetitive TMS was delivered at 20 Hz at 90% of the subjects resting motor threshold (RMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. SHAM: stimulation was delivered with the same TMS parameters as active simulation but the coil held at 90 degree to the scalp to induce similar somatic sensations and noise as in the active group with minimal brain effects. | 0 | 50 | 0 | 50 | 0 | 50 |
Not provided
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |