Cognitive Dysfunction in Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT02346708
• Recruitment Status: Active, not recruiting
• First Posted: January 27, 2015
• Results First Posted: December 9, 2020
• Last Update Posted: December 9, 2020
• Sponsor: University of Colorado, Denver
• Collaborators: National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): University of Colorado, Denver

Tracking Information

• First Submitted Date: January 9, 2015
• First Posted Date: January 27, 2015
• Results First Submitted Date: April 6, 2020
• Results First Posted Date: December 9, 2020
• Last Update Posted Date: December 9, 2020
• Study Start Date: January 2014
• Actual Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 20, 2015)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 8, 2020)

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)

Original Secondary Outcome Measures (submitted: January 20, 2015)

change in cognitive scores [ Time Frame: 2 weeks ]

Our behavioral outcome will be a change in the scores of the following tests: 1) Mattis Dementia Rating Scale 2) Executive function (Trails B, Verbal Fluency, Stroop); 3) Memory (Hopkins Verbal Learning Test); 4) Language (Boston Naming Test); 5) Attention (Brief Test of Attention); and 6) Visuospatial (Judgment of Line Orientation).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

• Device: Real TMS
  real treatment
  Other Name: Transcranial Magnetic Stimulation
• Device: Sham TMS
  placebo treatment

Study Arms

• 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.
  Intervention: Device: Real TMS
• 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.
  Intervention: Device: Sham TMS

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 8, 2020): 49
• Original Estimated Enrollment (submitted: January 20, 2015): 150
• Estimated Study Completion Date: December 2020
• Actual Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02346708
• Other Study ID Numbers: 13-2724; 1K02NS080885-01A1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

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

• Responsible Party: University of Colorado, Denver
• Study Sponsor: University of Colorado, Denver

Collaborators

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

Investigators

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

• PRS Account: University of Colorado, Denver
• Verification Date: December 2020