Cortico-cortical Stimulation and Robot-assisted Therapy for Upper Limb Recovery After Stroke (CCS&RAT)

NCT ID: NCT05478434

Last Updated: 2025-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-21

Study Completion Date

2025-10-31

Brief Summary

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The purpose of this study is to tested the effect of combination of a paired associative stimulation of two functional interconnected areas of the cerebral cortex (posterior-parietal cortex and primary motor cortex) with robot-assisted therapy in the recovery of upper limb after stroke.

Detailed Description

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BACKGROUND

Stroke survivors reported upper limb impairment that contribute to reducing the overall quality of life, social participation and professional activities. The impairment of the upper limb is due to motor and sensory alteration that could compromise the sensorimotor integration. The posterior parietal cortex (PPC) is a potential circuit where this integration could occur during active somatosensation. Indeed, PPC is a site of massive confluence of visual, tactile, proprioceptive, and vestibular signals. This area may be involved in transforming information about the location of targets in space, into signals related to motor intentions. This process likely occurs through parietal-motor connections, which are known to be involved in the transfer of relevant sensitive information for planning, reaching, and grasping. Paired associative stimulation (PAS) of PPC and primary motor area (M1), by means of bi-focal trans-cranial magnetic stimulation, can modulate M1 excitability. This information reinforces the hypothesis that modulation of PPC-M1 connectivity can be used as a new approach to modify motor excitability and sensorimotor interaction. Parallel, robot assisted training (RAT) can induce a plastic reorganization at the muscular afferents, spinal motor neurons, interneuron system and beyond and facilitates neural plasticity and motor relearning through goal-oriented training. The robotics device allows to train patients in an intensive, task-oriented, and top-down therapy way, increasing patients' compliance and motivation. The cognitive top-down stimulation is allowed by means of the introduction of visual feedback performed through exergaming. Recently, it has been proposed the development of new intervention strategies that combine neurostimulation of a target brain area with neurorehabilitation, such as physical therapy or virtual reality. Although both TMS and RAT have shown individually promising effects in upper limb recovery after a stroke, their combination has not been tested to date.

AIMS

1. To determine whether robot-assisted therapy combined with cortico-cortical non-invasive stimulation of M1 and PPC areas can improve functional recovery of upper extremity in patients with hemiparesis due to stroke.
2. To evaluate the feasibility of robot-assisted training exergaming technology for reaching and grasping training for stroke rehabilitation.
3. To investigate the neurophysiological changes in PPC-M1 connectivity (through TMS EEG) to clarify the effectiveness of PAS on neuromodulation of the PPC-M1 network.

Conditions

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Stroke Stroke, Ischemic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomised Clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
The recruiters, outcomes assessors, physical therapists, participants and their caregivers will be blinded with respect to participants' allocation for the entire period of the study.

Study Groups

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Robot and stimulation PPC-M1

Combined paired pulse stimulation (PAS) with robot-assisted therapy

Group Type EXPERIMENTAL

Cortico-cortical stimulation plus robot-assisted therapy

Intervention Type DEVICE

15 sessions of cortico-cortical stimulation between the PPC and the M1 of the lesioned hemisphere and robot-assisted therapy. Paired-pulse stimulation (PAS) technique, with 5ms inter-stimulus time between the two areas (PPC to M1), will be done through two high-power Magstim 200 machines (Magstim® Rapid²). To stimulate the M1 area, the coil will be placed tangentially to the scalp at a 45° angle to the midline, to stimulate the PPC area the center of the coil will be positioned over P4 (10-20 EEG system) tangentially to the skull with the handle pointing downward and slightly medial (10°). Robot-assisted therapy will be performed with an Armeo® Power II (Hocoma), an integrative system composed by a robotic exoskeleton device connected to a laptop for the audio-visual biofeedback for the upper limb therapy.

Robot and sham stimulation PPC-M1

Combined sham PAS with robot-assisted therapy

Group Type SHAM_COMPARATOR

Sham cortico-cortical stimulation plus robot-assisted therapy

Intervention Type DEVICE

15 sessions of sham cortico-cortical stimulation between the PPC and the M1 of the lesioned hemisphere and robot-assisted therapy. Sham paired-pulse stimulation (PAS) will be done through two high-power Magstim 200 machines (Magstim® Rapid²). To simulate the real stimulation, the coils will placed in the same sites with different inclination respect to the scalp (90°). Robot-assisted therapy will be performed with an Armeo® Power II (Hocoma), an integrative system composed by a robotic exoskeleton device connected to a laptop for the audio-visual biofeedback for the upper limb therapy.

Interventions

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Cortico-cortical stimulation plus robot-assisted therapy

15 sessions of cortico-cortical stimulation between the PPC and the M1 of the lesioned hemisphere and robot-assisted therapy. Paired-pulse stimulation (PAS) technique, with 5ms inter-stimulus time between the two areas (PPC to M1), will be done through two high-power Magstim 200 machines (Magstim® Rapid²). To stimulate the M1 area, the coil will be placed tangentially to the scalp at a 45° angle to the midline, to stimulate the PPC area the center of the coil will be positioned over P4 (10-20 EEG system) tangentially to the skull with the handle pointing downward and slightly medial (10°). Robot-assisted therapy will be performed with an Armeo® Power II (Hocoma), an integrative system composed by a robotic exoskeleton device connected to a laptop for the audio-visual biofeedback for the upper limb therapy.

Intervention Type DEVICE

Sham cortico-cortical stimulation plus robot-assisted therapy

15 sessions of sham cortico-cortical stimulation between the PPC and the M1 of the lesioned hemisphere and robot-assisted therapy. Sham paired-pulse stimulation (PAS) will be done through two high-power Magstim 200 machines (Magstim® Rapid²). To simulate the real stimulation, the coils will placed in the same sites with different inclination respect to the scalp (90°). Robot-assisted therapy will be performed with an Armeo® Power II (Hocoma), an integrative system composed by a robotic exoskeleton device connected to a laptop for the audio-visual biofeedback for the upper limb therapy.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. first ever chronic ischemic stroke;
2. hemiparesis due to left or right subcortical or cortical lesion in the territory of the middle cerebral artery;
3. severe or moderate residual upper limb impairment (FMA \< 52 in the motor domain A/D)

Exclusion Criteria

1. history of seizures;
2. severe general impairment or concomitant diseases;
3. treatment with benzodiazepines, baclofen, and antidepressants;
4. Intracranial metal implants;
5. cardiac pacemaker;
6. pregnancy status;
7. orthopedic contraindications for upper limb;
8. upper limb pain;
9. cognitive impairment (MMSE \< 23);
10. presence of unilateral spatial neglect
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Università degli studi di Roma Foro Italico

OTHER

Sponsor Role collaborator

I.R.C.C.S. Fondazione Santa Lucia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Giacomo Koch, prof.

Role: PRINCIPAL_INVESTIGATOR

IRCCS Santa Lucia Foundation

Locations

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Santa Lucia Foundation

Rome, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Giacomo Koch, prof.

Role: CONTACT

+390651501181

Facility Contacts

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Sonia Bonnì, PhD

Role: primary

+390651501181

References

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Hatem SM, Saussez G, Della Faille M, Prist V, Zhang X, Dispa D, Bleyenheuft Y. Rehabilitation of Motor Function after Stroke: A Multiple Systematic Review Focused on Techniques to Stimulate Upper Extremity Recovery. Front Hum Neurosci. 2016 Sep 13;10:442. doi: 10.3389/fnhum.2016.00442. eCollection 2016.

Reference Type RESULT
PMID: 27679565 (View on PubMed)

Mohan H, de Haan R, Mansvelder HD, de Kock CPJ. The posterior parietal cortex as integrative hub for whisker sensorimotor information. Neuroscience. 2018 Jan 1;368:240-245. doi: 10.1016/j.neuroscience.2017.06.020. Epub 2017 Jun 19.

Reference Type RESULT
PMID: 28642168 (View on PubMed)

Winstein CJ, Stein J, Arena R, Bates B, Cherney LR, Cramer SC, Deruyter F, Eng JJ, Fisher B, Harvey RL, Lang CE, MacKay-Lyons M, Ottenbacher KJ, Pugh S, Reeves MJ, Richards LG, Stiers W, Zorowitz RD; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Quality of Care and Outcomes Research. Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016 Jun;47(6):e98-e169. doi: 10.1161/STR.0000000000000098. Epub 2016 May 4.

Reference Type RESULT
PMID: 27145936 (View on PubMed)

Koch G, Fernandez Del Olmo M, Cheeran B, Schippling S, Caltagirone C, Driver J, Rothwell JC. Functional interplay between posterior parietal and ipsilateral motor cortex revealed by twin-coil transcranial magnetic stimulation during reach planning toward contralateral space. J Neurosci. 2008 Jun 4;28(23):5944-53. doi: 10.1523/JNEUROSCI.0957-08.2008.

Reference Type RESULT
PMID: 18524898 (View on PubMed)

Reti IM. Brain Stimulation: Methodologies and Interventions. John Wiley & Sons. 2015

Reference Type RESULT

Veniero D, Ponzo V, Koch G. Paired associative stimulation enforces the communication between interconnected areas. J Neurosci. 2013 Aug 21;33(34):13773-83. doi: 10.1523/JNEUROSCI.1777-13.2013.

Reference Type RESULT
PMID: 23966698 (View on PubMed)

Chao CC, Karabanov AN, Paine R, Carolina de Campos A, Kukke SN, Wu T, Wang H, Hallett M. Induction of motor associative plasticity in the posterior parietal cortex-primary motor network. Cereb Cortex. 2015 Feb;25(2):365-73. doi: 10.1093/cercor/bht230. Epub 2013 Aug 22.

Reference Type RESULT
PMID: 23968834 (View on PubMed)

Kwakkel G, Kollen BJ, Krebs HI. Effects of robot-assisted therapy on upper limb recovery after stroke: a systematic review. Neurorehabil Neural Repair. 2008 Mar-Apr;22(2):111-21. doi: 10.1177/1545968307305457. Epub 2007 Sep 17.

Reference Type RESULT
PMID: 17876068 (View on PubMed)

Morone G, Spitoni GF, De Bartolo D, Ghanbari Ghooshchy S, Di Iulio F, Paolucci S, Zoccolotti P, Iosa M. Rehabilitative devices for a top-down approach. Expert Rev Med Devices. 2019 Mar;16(3):187-195. doi: 10.1080/17434440.2019.1574567. Epub 2019 Feb 6.

Reference Type RESULT
PMID: 30677307 (View on PubMed)

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.

Reference Type RESULT
PMID: 30476999 (View on PubMed)

Chen YJ, Huang YZ, Chen CY, Chen CL, Chen HC, Wu CY, Lin KC, Chang TL. Intermittent theta burst stimulation enhances upper limb motor function in patients with chronic stroke: a pilot randomized controlled trial. BMC Neurol. 2019 Apr 25;19(1):69. doi: 10.1186/s12883-019-1302-x.

Reference Type RESULT
PMID: 31023258 (View on PubMed)

Palermo E, Hayes DR, Russo EF, Calabro RS, Pacilli A, Filoni S. Translational effects of robot-mediated therapy in subacute stroke patients: an experimental evaluation of upper limb motor recovery. PeerJ. 2018 Sep 4;6:e5544. doi: 10.7717/peerj.5544. eCollection 2018.

Reference Type RESULT
PMID: 30202655 (View on PubMed)

Cinnera AM, Bonni S, D'Acunto A, Maiella M, Ferraresi M, Casula EP, Pezzopane V, Tramontano M, Iosa M, Paolucci S, Morone G, Vannozzi G, Koch G. Cortico-cortical stimulation and robot-assisted therapy (CCS and RAT) for upper limb recovery after stroke: study protocol for a randomised controlled trial. Trials. 2023 Dec 21;24(1):823. doi: 10.1186/s13063-023-07849-1.

Reference Type DERIVED
PMID: 38129910 (View on PubMed)

Other Identifiers

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PROG.910

Identifier Type: -

Identifier Source: org_study_id

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