Interaction Between the Brain Hemispheres - Key to Motor Recovery After Stroke (InterAct)

Rationale: Acute stroke leaves many patients with functional deficits, of which upper extremity motor impairment is one of the most disabling. Evidence from imaging and electrophysiological studies converge on the idea that impaired motor function after stroke is associated with disrupted network activity in the brain. Non-invasive brain stimulation methods, like transcranial magnetic stimulation (TMS), can be used to restore disrupted network activity and have been shown to successfully facilitate recovery of motor function in patients with stroke. Application of continuous theta burst stimulation (cTBS), an inhibitory form of TMS, to the contralesional motor cortex has been shown to improve the recovery of motor function in patients with stroke. However, responsiveness to this treatment varies considerably between stroke patients and the mechanisms through which contralesional cTBS facilitates recovery of motor function remain unclear.

Objective: To determine if contralesional cTBS normalizes interhemispheric inhibition from the contralesional to ipsilesional primary motor cortex stroke patients with motor impairments. Age-matched healthy persons will serve as controls.

Study design: A prospective, open-label within-subject intervention study

Study population: 40 patients with first-ever ischemic stroke in one hemisphere and a unilateral paresis of the upper extremity, and 40 age-matched controls.

Main endpoints: Primary endpoint: Interhemispheric inhibition from the contralesional to ipsilesional primary motor cortex. Secondary endpoints: contralesional intracortical inhibition; effect of contralesional TMS interference on finger tapping frequency.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: cTBS

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jord Vink, PhD; Phone Number: +31634959811; Email: j.j.vink-5@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht
    • Utrecht, Utrecht, Netherlands
      • Recruiting
      • De Hoogstraat Revalidatie
      • Contact: Anne Visser-Meily, MD, PhD; Phone Number: +31 88 75 588 31; Email: j.m.a.visser-meily@umcutrecht.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for patients:

• Age ≥ 18 years;
• First-ever ischemic stroke or intracerebral hemorrhage in a cerebral hemisphere or the brainstem;
• Unilateral paresis of an upper extremity with a Motricity Index (MI) between 9 and 99
• Inclusion possible between 3 weeks and 6 weeks after stroke onset;
• Signed informed consent.

Inclusion Criteria for healthy controls:

• Age ≥ 18 years;
• Signed informed consent.
• Normal motor function with a minimum Motricity Index (MI) of 99.

Exclusion Criteria:

• Disabling medical conditions (severe heart disease, severe head trauma, severe mental illness);
• Severe deficits in communication, memory or understanding which could impede participation, as determined by the treating physician;
• Contraindications to TMS and/or MRI (ferrous implants, history of epilepsy, drug or alcohol abuse over a period of 6 months prior to the experiment, pregnancy);
• Life expectancy shorter than one year;
• Upper limb paresis prior to stroke onset.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active cTBS; cTBS delivered with an active TMS coil	Device: cTBS; A single cTBS session delivered to the contralesional primary motor cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interhemispheric inhibition (IHI)	Contralesional to ipsilesional IHI measured with a condition pulse delivered over the contralesional M1 and a test pulse delivered over the ipsilesional M1 with an interstimulus interval of 10ms. An aggregated measure (unitless) is obtained by dividing the conditioned motor-evoked potential (MEP) amplitude (in Volts) by the unconditioned MEP amplitude (in Volts). A value smaller than 1 indicates inhibition.	Within 30 minutes after cTBS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ipsilesional resting motor threshold (RMT)	Ipsilesional RMT in percentage of machine output. Outcome ranges from 0 to 100%.	Within 30 minutes after cTBS
Contralesional resting motor threshold (RMT)	Contralesional RMT in percentage of machine output. Outcome ranges from 0 to 100%.	Within 30 minutes after cTBS
TMS interference	Finger tapping frequency change in response to TMS interference of the contralesional M1.	Within 30 minutes after cTBS
Intracortical inhibition (ICI)	Intracortical inhibition in the contralesional M1 with an interstimulus interval of 2ms. An aggregated measure (unitless) is obtained by dividing the conditioned motor-evoked potential (MEP) amplitude (in Volts) by the unconditioned MEP amplitude (in Volts). A value smaller than 1 indicates inhibition.	Within 30 minutes after cTBS

Collaborators and Investigators

• Sponsor: Jord Vink

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 17, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Stroke; Transcranial magnetic stimulation; TMS; cTBS; Continuous theta burst stimulation; Upper limb recovery; Interhemispheric inhibition
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: NL86587.041.24

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
• product manufactured in and exported from the U.S.: No