NCT06911671

Brief Summary

The investigators hypothesize that a myoelectric (EMG) controlled virtual reality (VR) interface allows for effective upper limb motor recovery of stroke patients. EMG control offers the possibility to alter visual feedback according to the recorded muscle activity in real-time. By manipulating the motion of a virtual hand associated with the recorded muscle patterns, assistance can be provided to stroke patients by correcting the error between the actual (dysfunctional) and a reference (functional) muscle pattern. Thus, through such an assistive EMG control algorithm, patients will be able to perform reaching movements with the virtual hand despite their motor impairment. By gradually reducing assistance, it is hypothesized that the salient error in the task space provided as visual feedback will systematically change the muscle patterns, thereby driving adaptation of the dysfunctional muscle patterns, enhancing motor recovery. Moreover, due to its relevant role in motor learning, it is expected that cerebellar stimulation will favor the underlying processes of adapting cerebello-cortical plasticity involved in motor learning. Therefore, it is hypothesized that an assistive EMG control algorithm in combination with cerebellar transcranial magnetic stimulation will further enhance upper limb recovery.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for not_applicable stroke

Timeline
17mo left

Started Apr 2025

Typical duration for not_applicable stroke

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress44%
Apr 2025Oct 2027

First Submitted

Initial submission to the registry

February 3, 2023

Completed
2.2 years until next milestone

Study Start

First participant enrolled

April 1, 2025

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 4, 2025

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2027

Last Updated

February 3, 2026

Status Verified

March 1, 2025

Enrollment Period

2.3 years

First QC Date

February 3, 2023

Last Update Submit

January 30, 2026

Conditions

StrokeStroke, Cardiovascular

Keywords

Virtual RealityBrain StimulationMyoelectric ControlTranscranial Magnetic StimulationCerebellar StimulationMotor RecoveryTailored Assistance

Outcome Measures

Primary Outcomes (1)

  • Change in the Fugl-Meyer Assessment Scale for Upper Extremity (FMA-UE)

    Comprehensive clinical measurement tool of upper limb functions after stroke. Range score form 0 to 66 points, a higher score represents an improvement.

    baseline: T0, post-treatment (3 weeks): T1, follow-up (6 weeks from T1): T2.

Secondary Outcomes (6)

  • Change in the Box and Block test (BBT)

    baseline: T0, post-treatment (3 weeks): T1, follow-up (6 weeks from T1): T2.

  • Change in modified Barthel Index (mBI) score

    baseline: T0, post-treatment (3 weeks): T1, follow-up (6 weeks from T1): T2.

  • Change in the Nine Hole Peg Test (NHPT)

    baseline: T0, post-treatment (3 weeks): T1, follow-up (6 weeks from T1): T2.

  • Change in muscle activation patterns (EMG)

    baseline: T0, post-treatment (3 weeks): T1, follow-up (6 weeks from T1): T2.

  • Change in force-control

    baseline: T0, post-treatment (3 weeks): T1, follow-up (6 weeks from T1): T2.

  • +1 more secondary outcomes

Study Arms (3)

EMG-VR real c-iTBS

EXPERIMENTAL

Subjects will perform 12 sessions (\~30 minutes, 3 times per weeks for 4 weeks) of assisted EMG control task (aEC) after real cerebellar intermittent theta burst stimulation (c-iTBS) for paretic upper limb.

Device: Virtual Reality Interface + Cerebellar iTBS (c-iTBS)

EMG-VR sham c-iTBS

SHAM COMPARATOR

Subjects will perform 12 sessions (\~30 minute, 3 times per weeks for 4 weeks) of assisted EMG control task (aEC) after sham cerebellar intermittent theta burst stimulation (c-iTBS) for paretic upper limb.

Device: Virtual Reality + Sham Cerebellar iTBS (sham c-iTBS)

Conventional Physical Therapy

ACTIVE COMPARATOR

Subjects will perform 12 sessions (\~30 minutes, 3 times per weeks for 4 weeks) of physical therapy targeting on motor functionality of upper limb.

Other: Physical Therapy

Interventions

Virtual Reality + Sham Cerebellar iTBS (sham c-iTBS)DEVICE

c-iTBS will be carried out using Magstim Rapid magnetic biphasic stimulator. Twenty 2-s trains of three-pulse bursts at 50 Hz repeated every 200 ms with an inter-train interval of 10 s, for a total of 190 s will be applied over the contralesional lateral cerebellum. The coil will be positioned tangentially to the scalp for real and 90° angled for sham c-iTBS.

EMG-VR sham c-iTBS
Physical TherapyOTHER

Passive mobilization and motor recruitment of impaired upper limb will be performed with the support of a physical therapist specialized in neurological rehabilitation.

Conventional Physical Therapy
Virtual Reality Interface + Cerebellar iTBS (c-iTBS)DEVICE

Subjects will sit in a chair with their forearm inserted in a splint attached to a force transducer. The subjects' view of their hand will be occluded by a mirror displaying the virtual scene. EMGs from arm and shoulder muscles will be recorded by surface EMG electrodes. Subjects will displace a virtual handle according to either the forces recorded by the force transducer or forces estimated from the recorded EMGs (EMG control).

EMG-VR real c-iTBS

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • First ever ischemic stroke with mild to moderate motor impairment of upper limb;
  • Left or right sub-cortical or cortical lesion of the middle cerebral artery;
  • Age\>18, \<80 years;
  • No visuospatial, cognitive, or attention deficits;
  • Fugl-Meyer score\<56.

You may not qualify if:

  • History of seizures;
  • Treatment with Benzodiazepines, Baclofen;
  • Pregnancy status;
  • Intracranial metal implant;
  • Cardiac pace-maker;
  • Orthopedic upper limb limitation;
  • Upper limb pain;
  • Patients with neurological diseases beyond stroke or with neuropsychiatric disorders or with neuropsychological disorders that could potentially compromise informed consent or compliance during the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IRCCS Santa Lucia Foundation

Roma, Rome, 00179, Italy

RECRUITING

Related Publications (6)

  • Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

    PMID: 15664172BACKGROUND

  • Hummel FC, Cohen LG. Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke? Lancet Neurol. 2006 Aug;5(8):708-12. doi: 10.1016/S1474-4422(06)70525-7.

    PMID: 16857577BACKGROUND

  • Spampinato D, Celnik P. Deconstructing skill learning and its physiological mechanisms. Cortex. 2018 Jul;104:90-102. doi: 10.1016/j.cortex.2018.03.017. Epub 2018 Mar 27.

    PMID: 29775838BACKGROUND

  • Celnik P. Understanding and modulating motor learning with cerebellar stimulation. Cerebellum. 2015 Apr;14(2):171-4. doi: 10.1007/s12311-014-0607-y.

    PMID: 25283180BACKGROUND

  • Berger DJ, Gentner R, Edmunds T, Pai DK, d'Avella A. Differences in adaptation rates after virtual surgeries provide direct evidence for modularity. J Neurosci. 2013 Jul 24;33(30):12384-94. doi: 10.1523/JNEUROSCI.0122-13.2013.

    PMID: 23884944BACKGROUND

  • Koch G, Bonni S, Casula EP, Iosa M, Paolucci S, Pellicciari MC, Cinnera AM, Ponzo V, Maiella M, Picazio S, Sallustio F, Caltagirone C. Effect of Cerebellar Stimulation on Gait and Balance Recovery in Patients With Hemiparetic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2019 Feb 1;76(2):170-178. doi: 10.1001/jamaneurol.2018.3639.

    PMID: 30476999BACKGROUND

MeSH Terms

Conditions

StrokeMyocardial Infarction

Interventions

Physical Therapy Modalities

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesMyocardial IschemiaHeart DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Intervention Hierarchy (Ancestors)

TherapeuticsRehabilitation

Study Officials

  • Giacomo Koch, Prof.

    IRCCS Santa Lucia Foundation

    STUDY CHAIR

Central Study Contacts

Giacomo Koch, Prof.

CONTACT

0039 0651501181g.koch@hsantalucia.it

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 3, 2023

First Posted

April 4, 2025

Study Start

April 1, 2025

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

October 1, 2027

Last Updated

February 3, 2026

Record last verified: 2025-03

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)