Theta Burst Stimulation to Promote Motor Re-education in Tetraplegia

Intermittent Theta Burst Stimulation to Promote Motor Re-education After Upper Limb Reconstruction in Tetraplegia

A repetitive, non-invasive brain stimulation technique referred to as theta burst stimulation can modulate corticomotor excitability and therefore has great rehabilitative potential for individuals with neurologic deficits, including individuals with spinal cord injury (SCI). In particular, intermittent theta burst stimulation (iTBS) can increase corticomotor excitability and may be a useful adjunct to physical rehabilitation to promote motor re-education after upper limb reconstruction in individuals with tetraplegia. Upper limb reconstruction involves surgical transfer of a non-paralyzed tendon or nerve with a redundant or less important function to perform a more critical function. Upper limb reconstruction is intended to help individuals achieve their goals related to activities of daily living and independence in the community. Outcomes after reconstruction are variable and depend largely on the efficacy of motor re-education of the transferred muscle to perform a new function. The long-term goal of our research is to determine whether iTBS combined with physical rehabilitation can improve motor re-education after reconstruction. As a first step, the purpose of this proposal is to determine the effect of iTBS on corticomotor excitability of proximal muscles in nonimpaired individuals and two groups of individuals with tetraplegia: individuals with and without upper limb reconstruction.

Study Overview

• Status: Completed
• Conditions: Quadriplegia/Tetraplegia
• Intervention / Treatment: Other: Intermittent theta burst stimulation

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for all subjects with tetraplegia:

• Injury to the lower cervical spinal cord at least one year prior to the date of participation
• Motor function classified according to the American Spinal Injury Association International Standards for Neurological Classification of Spinal Cord Injury at levels ranging from C5-C8

Inclusion criteria for the subjects with tetraplegia and upper limb reconstruction:

• At least one year post-operative from tendon or nerve transfer surgery of the upper limb

Exclusion criteria for all subjects with tetraplegia:

• Presence of concurrent severe medical illness, including unhealed decubiti, use of baclofen pumps, existing infection, cardiovascular disease, significant osteoporosis, or a history of pulmonary complications.
• Metal implant near head or neck
• Risk of seizure of history of seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Neurologically Normal; Neurologically normal subjects (i.e., nonimpaired) will be recruited for participation in three sessions of intermittent theta burst stimulation (iTBS), each consisting of sham iTBS applied to the hotspot of the target muscle and active iTBS; sham iTBS always be will administered first to minimize the potential for carry over effects. Sessions will be separated by at least 3 days to minimize the potential for carry over effects. Before and 10, 20 and 30 minutes after each iTBS session, motor evoked potentials (MEPs) will be recorded in order to quantify changes in corticomotor excitability.	Other: Intermittent theta burst stimulation; Intermittent theta burst stimulation (iTBS) is a non-invasive brain stimulation technique that can increase corticomotor excitability.
Active Comparator: Quadriplegia; Individuals with quadriplegia will be recruited for participation in three sessions of intermittent theta burst stimulation (iTBS), each consisting of sham iTBS applied to the hotspot of the target muscle and active iTBS; sham iTBS always be will administered first to minimize the potential for carry over effects. Sessions will be separated by at least 3 days to minimize the potential for carry over effects. Before and 10, 20 and 30 minutes after each iTBS session, motor evoked potentials (MEPs) will be recorded in order to quantify changes in corticomotor excitability.	Other: Intermittent theta burst stimulation; Intermittent theta burst stimulation (iTBS) is a non-invasive brain stimulation technique that can increase corticomotor excitability.
Active Comparator: Quadriplegia with upper limb reconstruction; Individuals with quadriplegia and upper limb reconstruction will be recruited for participation in three sessions of intermittent theta burst stimulation (iTBS), each consisting of sham iTBS applied to the hotspot of the target muscle and active iTBS; sham iTBS always be will administered first to minimize the potential for carry over effects. Sessions will be separated by at least 3 days to minimize the potential for carry over effects. Before and 10, 20 and 30 minutes after each iTBS session, motor evoked potentials (MEPs) will be recorded in order to quantify changes in corticomotor excitability.	Other: Intermittent theta burst stimulation; Intermittent theta burst stimulation (iTBS) is a non-invasive brain stimulation technique that can increase corticomotor excitability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in corticomotor excitability	Corticomotor excitability will be measured via motor evoked potential amplitudes in response to transcranial magnetic stimulation	Each subject will participate in five sessions, each session separated by 3 days. After each session, changes in corticomotor excitability will be measured. Changes in excitability will be reported through study completion, an average of one month.

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: Medical University of South Carolina; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Carrie L Peterson, PhD, Virginia Commonwealth University

Publications and helpful links

General Publications

• Mittal N, Majdic BC, Peterson CL. Intermittent theta burst stimulation modulates biceps brachii corticomotor excitability in individuals with tetraplegia. J Neuroeng Rehabil. 2022 Jul 17;19(1):73. doi: 10.1186/s12984-022-01049-9.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: August 24, 2017
• First Submitted That Met QC Criteria: September 5, 2017
• First Posted (Actual): September 11, 2017

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 13, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Paralysis; Quadriplegia
• Other Study ID Numbers: HM20010643; P2CHD086844 (U.S. NIH Grant/Contract); FP00005482 (Other Identifier: Virginia Commonwealth University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No