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Cognitive Dysfunction in Parkinson's Disease

Primary Purpose

Parkinson's Disease

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Real TMS
Sham TMS
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's, TMS, Kluger

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of probable PD (using United Kingdom Brain Bank criteria)
  • Diagnosis of mild cognitive impairment
  • No unstable medical condition

Exclusion Criteria:

  • Features suggestive of other causes of Parkinsonism or other neurological disorders
  • Prior deep brain stimulation (DBS) or ablation surgery
  • Evidence for active depression or Hospital Anxiety and Depression Scale (HADS) score greater than or equal to 11
  • Motor symptoms expected to interfere with scanning (e.g. sever tremor)
  • Contraindications to TMS, MEG, or MRI such as pregnancy, pacemaker, unstable cardiac disease, skull lesion, claustrophobia, history of epilepsy, or on medications known to lower seizure threshold
  • Implanted electronic devices or metal

Sites / Locations

  • University of Colorado School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Real TMS

Sham TMS

Arm Description

TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and left pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% 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. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease.52, 123 Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.

Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Outcomes

Primary Outcome Measures

Change in Magnetoencephalography (MEG) Connectivity Measures
Our MEG outcome will be a change in small-worldness, global efficiency, nodal efficiency and degree distribution pre-TMS to immediately post-TMS treatment.

Secondary Outcome Measures

Post-TMS Change From Baseline in Cognitive Scores
Our behavioral outcome will be a change in the scores of the following tests: Mattis Dementia Rating Scale: Higher raw scores = better cognitive status, ranging from 0 to 144. Normative data in healthy subjects range from 137 to 144. Trail Making Test Trails B: average score is 75 seconds; deficient score is > 273 seconds. Delis-Kaplan Executive Function System (DKEFS) - Verbal Fluency Test. Higher score = higher ability in language processing. Scales scores vary from 0 min to N/A max (no concrete maximum). DKEFS - Stroop Interference Test measures inhibitory control and cognitive flexibility. Performance is measured by completion time. No min or max value for this test. Test should be discontinued after 90 sec. For those, higher scores = higher abilities: California Verbal Learning Test (declarative memory, scale 0 to 80), Boston Naming Test (language, scale 0 to 60), Brief Test of Attention and Judgment of Line Orientation (scale 0 to 30)

Full Information

First Posted
January 9, 2015
Last Updated
January 21, 2021
Sponsor
University of Colorado, Denver
Collaborators
National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT02346708
Brief Title
Cognitive Dysfunction in Parkinson's Disease
Official Title
Cortical Physiology as a Therapeutic Target in Parkinson's Disease Related Dementia and Cognitive Dysfunction
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study plans to learn more about the brain function related to thinking problems in individuals with Parkinson's disease.
Detailed Description
Dementia is the leading cause of nursing home placement in Parkinson's disease (PD) yet little is known about the cause(s) of cognitive dysfunction in PD and there are no effective treatments. The investigators preliminary data and other published studies suggest that abnormalities in brain activity involving networks important for normal thinking and memory may contribute to cognitive dysfunction in PD and may represent a target for treatment. This proposal will identify abnormalities in cortical activity related to cognitive dysfunction in PD using magnetoencephalography and will perform a randomized control trial of bifrontal repetitive transcranial magnetic stimulation to determine the therapeutic potential of modulating this brain activity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's, TMS, Kluger

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Real TMS
Arm Type
Experimental
Arm Description
TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and left pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% 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. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease.52, 123 Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.
Arm Title
Sham TMS
Arm Type
Sham Comparator
Arm Description
Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.
Intervention Type
Device
Intervention Name(s)
Real TMS
Other Intervention Name(s)
Transcranial Magnetic Stimulation
Intervention Description
real treatment
Intervention Type
Device
Intervention Name(s)
Sham TMS
Intervention Description
placebo treatment
Primary Outcome Measure Information:
Title
Change in Magnetoencephalography (MEG) Connectivity Measures
Description
Our MEG outcome will be a change in small-worldness, global efficiency, nodal efficiency and degree distribution pre-TMS to immediately post-TMS treatment.
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Post-TMS Change From Baseline in Cognitive Scores
Description
Our behavioral outcome will be a change in the scores of the following tests: Mattis Dementia Rating Scale: Higher raw scores = better cognitive status, ranging from 0 to 144. Normative data in healthy subjects range from 137 to 144. Trail Making Test Trails B: average score is 75 seconds; deficient score is > 273 seconds. Delis-Kaplan Executive Function System (DKEFS) - Verbal Fluency Test. Higher score = higher ability in language processing. Scales scores vary from 0 min to N/A max (no concrete maximum). DKEFS - Stroop Interference Test measures inhibitory control and cognitive flexibility. Performance is measured by completion time. No min or max value for this test. Test should be discontinued after 90 sec. For those, higher scores = higher abilities: California Verbal Learning Test (declarative memory, scale 0 to 80), Boston Naming Test (language, scale 0 to 60), Brief Test of Attention and Judgment of Line Orientation (scale 0 to 30)
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of probable PD (using United Kingdom Brain Bank criteria) Diagnosis of mild cognitive impairment No unstable medical condition Exclusion Criteria: Features suggestive of other causes of Parkinsonism or other neurological disorders Prior deep brain stimulation (DBS) or ablation surgery Evidence for active depression or Hospital Anxiety and Depression Scale (HADS) score greater than or equal to 11 Motor symptoms expected to interfere with scanning (e.g. sever tremor) Contraindications to TMS, MEG, or MRI such as pregnancy, pacemaker, unstable cardiac disease, skull lesion, claustrophobia, history of epilepsy, or on medications known to lower seizure threshold Implanted electronic devices or metal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benzi M Kluger, MD, MS
Organizational Affiliation
University of Colorado School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado School of Medicine
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified data will be made available to the scientific community upon request.

Learn more about this trial

Cognitive Dysfunction in Parkinson's Disease

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