- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02468804
Cognitive Dysfunction In Parkinson's (KL2)
Cognitive Dysfunction in Parkinson's Disease
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Colorado
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Aurora, Colorado, United States, 80045
- UC Denver Building 534
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- We will recruit 60 PD patients through the University Colorado Hospital (UCH) Movement Disorders Clinic diagnosed with probable PD using United Kingdom (UK) Brain Bank Criteria.
- PD patients will be of mild to moderate severity based on the Hohn and Yahr scale (score of 3 or less in on medication state) and be on a stable dose of PD medications.
- Clinical severity will also be assessed using the Unified Parkinson Disease Rating Scale.
- We do not anticipate recruitment to be difficult as UCH Movement clinics see over 800 PD patients annually, the majority of whom are stage 3 or less.
- Controls will be approximately matched for age and gender as a group and recruited through clinic (spouses) and advertisements in the community.
Exclusion Criteria:
- Subjects will be excluded if they have significant depression (Beck Depression Inventory33 > 14)
- Dementia (Mini Mental State Examination34 < 26 or Frontal Assessment Battery35 < 14)
- Other neurological or psychiatric illness
- Significant history of head injury, significant systemic medical diseases (e.g. liver failure, kidney failure, poorly controlled diabetes)
- Deep Brain Stimulation (DBS)
- Cognitive enhancing medications (e.g. stimulants or acetylcholinesterase inhibitors) or contraindications to either TMS or MRI (pregnancy, pacemaker, unstable cardiac disease, skull lesion, claustrophobia, history of epilepsy or on medications known to lower seizure threshold).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Parkinson's Disease Subjects, (rTMS)
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
|
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.
Other Names:
|
Experimental: Control Subjects (rTMS)
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
|
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.
Other Names:
|
Sham Comparator: Parkinson's Disease Subjects, (sTMS)
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
|
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.
|
Sham Comparator: Control Subjects (sTMS)
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
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Differences in Error Rates on the NBack Task Between Real and Sham Stimulation Trials
Time Frame: Change immediately after a single session TMS (pre will be done 1 week prior)
|
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)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Benzi Kluger, MD, University of Colorado, Denver
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 10-0771
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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