Cognitive Dysfunction in Parkinson's Disease

January 21, 2021 updated by: University of Colorado, Denver

Cortical Physiology as a Therapeutic Target in Parkinson's Disease Related Dementia and Cognitive Dysfunction

This study plans to learn more about the brain function related to thinking problems in individuals with Parkinson's disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Real TMS
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.
Device: Real TMS
real treatment
Other Names:
  • Transcranial Magnetic Stimulation
Sham Comparator: Sham TMS
Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.
Device: Sham TMS
placebo treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Magnetoencephalography (MEG) Connectivity Measures
Time Frame: 2 weeks
Our MEG outcome will be a change in small-worldness, global efficiency, nodal efficiency and degree distribution pre-TMS to immediately post-TMS treatment.
2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-TMS Change From Baseline in Cognitive Scores
Time Frame: 2 weeks

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)
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Benzi M Kluger, MD, MS, University of Colorado School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

January 9, 2015

First Submitted That Met QC Criteria

January 20, 2015

First Posted (Estimate)

January 27, 2015

Study Record Updates

Last Update Posted (Actual)

February 9, 2021

Last Update Submitted That Met QC Criteria

January 21, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-2724
  • 1K02NS080885-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

De-identified data will be made available to the scientific community upon request.

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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