rTMS to Improve Cognition in Parkinson's (TMSCogReP)

rTMS as a Cognitive Rehabilitation Approach in Veterans With Parkinson'sDisease

The purpose of this study is to examine safety, feasibility, and the behavioral and brain effects of a non-invasive treatment, repetitive transcranial magnetic stimulation (rTMS), for Veterans with Parkinson's disease and mild impairments in their thinking. The hypothesis is that rTMS can improve thinking for people with Parkinson's disease who are experiencing mild problems with their thinking ability.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease; Mild Cognitive Impairment
• Intervention / Treatment: Device: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark); Device: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark)

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) shows promise as an effective cognitive neurorehabilitation treatment. To date, no rTMS studies have assessed the effect of rTMS on cognitive function in PD-MCI. Nor has there been PD neurophysiological studies using rTMS to examine neural plasticity in cognitive neural networks. This study seeks to fill this gap by conducting a small scaled pilot randomized controlled trial (RCT) designed to assess the safety and therapeutic effects of rTMS on cognitive outcomes as well as on brain connectivity in Veterans with PD-MCI. PD-MCI participants will be randomized to either active rTMS or sham rTMS. Participants will complete a standardized neurocognitive battery assessment at baseline, endpoint and at a one month follow-up. The primary outcome is change in executive function. Secondary outcomes include performance on other cognitive domain tasks and a proximal measure of real-life function that captures relevant functional changes related to cognitive impairment in PD. Multi-modal neuroimaging, in a subsample of participants, will be used to study neural connectivity changes induced by rTMS. Changes in resting state functional connectivity, grey matter volume via voxel-based morphometry and white matter integrity via diffusion tensor imaging will be assessed at baseline and endpoint. To inform how to optimize rTMS treatment in PD-MCI, these changes will be correlated with changes in cognitive performance.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sandra L Kletzel, PhD BA; Phone Number: (708) 202-5735; Email: Sandra.Kletzel@va.gov
• Study Contact Backup: Name: Elyse R Walsh, DPT; Phone Number: (708) 968-0427; Email: elyse.walsh@va.gov

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Jesse Brown VA Medical Center, Chicago, IL
      • Contact: Sandra L Kletzel, PhD; Phone Number: 708-202-5735; Email: sandra.kletzel@va.gov
      • Contact: Elyse Walsh, MS; Phone Number: 7089680427; Email: elyse.walsh@va.gov
    • Hines, Illinois, United States, 60141-3030
      • Recruiting
      • Edward Hines Jr. VA Hospital, Hines, IL
      • Contact: William Wolf, PhD; Phone Number: 708-202-5689; Email: William.Wolf@va.gov
      • Principal Investigator: Sandra L. Kletzel, PhD BA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Veterans who seek services at Hines VA Hospital or Jesse Brown VA Medical Center
• Diagnosis of PD as determined by the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria
• Meet criteria for having mild cognitive impairment
• Receiving stable (i.e., no changes in medication and medication dose) medication and who are expected to remain on stable medication for the duration of the RCT
• Speak and read English
• 50 years or older

Exclusion Criteria:

• Dementia
• Failure to demonstrate decision making capacity
• History of deep brain stimulation surgery
• Severe depression
• Resting head tremor
• Dyskinesia that will interfere with collecting imaging data
• Has congestive heart failure
• Implanted cardiac pacemaker or defibrillator
• Cochlear implant, nerve stimulator, or intracranial metal clips
• Implanted medical pump
• Increased intracranial pressure
• History of claustrophobia
• Metal in eyes/face, shrapnel/bullet remnants in brain

• Participants at potential increased risk of seizure including those who have the following:

  • history (or family history) of seizure or epilepsy
  • history of stroke, head injury, or unexplained seizures

  • presence of other neurological disease that may be associated with an altered seizure threshold

    • such as CVA, cerebral aneurysm, dementia, increased intracranial pressure
• Concurrent medication use such as tricyclic antidepressants, neuroleptic medications, any other drug known to lower seizure threshold
• Secondary conditions that may significantly alter electrolyte balance or lower seizure threshold
• No quantifiable motor threshold such that rTMS dosage cannot be accurately deter-mined

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active rTMS; For active rTMS, a butterfly coil and MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark) will be used. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.	Device: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark); The coil will be held tangentially to the skull at approximately 45º from the midline. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.; Device: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark); The coil will be held tangentially to the skull at approximately 45º from the midline. The sham coil will not release any stimulation, but it will look, feel and sound like the real rTMS
Sham Comparator: sham rTMS; For sham rTMS, the procedure will be carried out at the left DLPFC but a sham coil will be used. The MagVenture coil has an active side and a placebo side allowing a double-blind study to be conducted. The sham system looks, sounds and feels like active rTMS.	Device: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark); The coil will be held tangentially to the skull at approximately 45º from the midline. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.; Device: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark); The coil will be held tangentially to the skull at approximately 45º from the midline. The sham coil will not release any stimulation, but it will look, feel and sound like the real rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in NIH sponsored Executive Abilities: Measures and Instruments for neurobehavioral evaluation and re-search (NIH-EXAMINER) executive composite score	The NIH-EXAMINER has an established 3-factor model defined by (1) cognitive control, (2) working memory (3) fluency. A confirmatory factor analysis indicates these 3-factors load on to 1-factor: executive composite score. Seven tests in the NIH-EXAMINER will be used to compute the composite score	baseline, 8 weeks, 12 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Sandra L. Kletzel, PhD BA, Edward Hines Jr. VA Hospital, Hines, IL

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Estimated): June 26, 2024
• Study Completion (Estimated): June 16, 2025

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 11, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: rTMS; mild cognitive impairment; neuromodulation; Parkinson's disease; executive function; functional connectivity
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Parkinson Disease; Cognitive Dysfunction
• Other Study ID Numbers: N2938-W; IK2RX002938 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Raw and/or normalized data will be made available in the form of Excel files. MRI images will anonymized and made available through the Northwestern University Neuroimaging Data Archive (NUNDA).
• IPD Sharing Time Frame: Final data sets will be made available as per Hines VA Hospital local policy for long term storage and access until enterprise-level resources become available.
• IPD Sharing Access Criteria: These data will be available upon request by researchers and scientists in accordance with federal guidelines and Hines local policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No