Parkinson'sKL2NCT02468804
Cognitive Dysfunction In Parkinson's
A study testing rTMS in people with Parkinson's, run by University of Colorado, Denver at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 45 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson's
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Nov 2016
- 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 45 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cognitive Dysfunction in Parkinson's Disease
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.
Read the 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.
- Conditions
- Parkinson's
- Being tested
- rTMS, Sham TMS
- Keywords
- Parkinson's, Non-parkinsons
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
Also called Repetitive Transcranial Magnetic Stimulation
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.
Sham TMSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Device: rTMS |
| 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 Receives: Device: rTMS |
| 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 Receives: Device: Sham TMS |
| 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 Receives: Device: Sham TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change immediately after a single session TMS (pre will be done 1 week prior)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study startAug 2013
- Primary completionNov 2016
- Study completionNov 2016
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'sStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benzi Kluger, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02468804
- Sponsor's protocol ID
- 10-0771
- Acronym
- KL2
- Status last verified
- Jul 2021
- First submitted
- 18 Oct 2013
- Last updated
- 27 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: In Progress
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Dysfunction in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02468804
- Acronym / sponsor ID
- KL2 / 10-0771
- Conditions
- Parkinson's
- Keywords
- Parkinson's, Non-parkinsons
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 11 Jun 2015 (estimated)
- Results
- Posted 27 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Parkinson's Disease Subjects, (rTMS) | Experimental | Device: rTMSThe 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 | Device: rTMSThe 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 | Device: Sham TMSThe 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 | Device: Sham TMSThe 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 |
Who may qualify
- Ages
- 45 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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)
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 |
|---|---|---|
| rTMSAlso: Repetitive Transcranial Magnetic StimulationTMS: 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. | Device | Control Subjects (rTMS), Parkinson's Disease Subjects, (rTMS) |
| Sham TMSSham 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. | Device | Control Subjects (sTMS), Parkinson's Disease Subjects, (sTMS) |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. In Progress
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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.
Benzi Kluger, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Parkinson's, run by University of Colorado, Denver 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 6 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 27 Jul 2021. 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 27 Jul 2021). 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?
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)). 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 27 Jul 2021.