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

November 11, 2022 updated by: I.R.C.C.S. Fondazione Santa Lucia

Cortico-cortical Stimulation and Robot-assisted Therapy a New Approach of Upper Limb Functional Recovery After Stroke

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

32

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Rome, Italy, 00179
        • Recruiting
        • Santa Lucia foundation
        • Contact:
        • Sub-Investigator:
          • Giuseppe Vannozzi, Prof
        • Sub-Investigator:
          • Alex Martino Cinnera, MSc
        • Sub-Investigator:
          • Alessia D'Acunto, BSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Robot and stimulation PPC-M1
Combined paired pulse stimulation (PAS) with robot-assisted therapy
Device: 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.
Sham Comparator: Robot and sham stimulation PPC-M1
Combined sham PAS with robot-assisted therapy
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Fugl-Meyer Assessment Scale for Upper Extremity (FMA-UE)
Time Frame: baseline; 3weeks (end of treatment); 7weeks (follow-up)
Comprehensive clinical measurement tool of upper limb functions after stroke. Range score form 0 to 66 points, a higher score represents an improvement.
baseline; 3weeks (end of treatment); 7weeks (follow-up)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Box and Block Test
Time Frame: baseline; 3weeks (end of treatment); 7weeks (follow-up)
Clinical test of motor function of upper limb after stroke.
baseline; 3weeks (end of treatment); 7weeks (follow-up)
Change in the Modified Ashworth Scale
Time Frame: baseline; 3weeks (end of treatment); 7weeks (follow-up)
Clinical Scale used to assessed spasticity. Range score from 0 to 5, a lower score represents an improvement.
baseline; 3weeks (end of treatment); 7weeks (follow-up)
Change in the functional movements of upper limb
Time Frame: baseline; 3weeks (end of treatment); 7weeks (follow-up)
Change in the kinematics variables will be recorded via inertial measurement units and motion-analysis during a three-reaching tasks and the Box-and-Block test.
baseline; 3weeks (end of treatment); 7weeks (follow-up)
Change in the cortical excitability
Time Frame: baseline; 3weeks (end of treatment); 7weeks (follow-up)
Stimulating a specific area with a single pulse of TMS evoke a so called Transcranial Evoked Potential (TEP), which is a well-know index of cortical excitability of the stimulated cortical area .
baseline; 3weeks (end of treatment); 7weeks (follow-up)
Change in the cortical oscillations
Time Frame: baseline; 3weeks (end of treatment); 7weeks (follow-up)
From TMS-EEG recording it is possible to analyze oscillatory activity of the stimulated brain area. Monitoring the frequency band during time after TMS-pulse we calculate Time-frequency Wavelets and from there the TMS-related spectral perturbation (TRSP) as output of the frequency bands (Delta, Theta, Alpha, Beta, Gamma) expressed.
baseline; 3weeks (end of treatment); 7weeks (follow-up)
Change in the cortical connectivity
Time Frame: baseline; 3weeks (end of treatment); 7weeks (follow-up)
Monitoring how TMS-pulse spreads from the stimulated area to the other areas, it is possible to assess the effective connectivity that area has with a widespread of network connected. So we calculate the Coherence between different areas and other connectivity indexes in the cortical oscillatory domain, i.e. Phase-locking Value (PLV) and Phase-amplitude coupling (PAC)
baseline; 3weeks (end of treatment); 7weeks (follow-up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

Università degli studi di Roma Foro Italico

Investigators

  • Principal Investigator: Giacomo Koch, prof., IRCCS Santa Lucia Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 21, 2022

Primary Completion (Anticipated)

August 1, 2023

Study Completion (Anticipated)

October 1, 2023

Study Registration Dates

First Submitted

July 6, 2022

First Submitted That Met QC Criteria

July 26, 2022

First Posted (Actual)

July 28, 2022

Study Record Updates

Last Update Posted (Actual)

November 16, 2022

Last Update Submitted That Met QC Criteria

November 11, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PROG.910

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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