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

Sponsor
I.R.C.C.S. Fondazione Santa Lucia (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05478434
Collaborator
Università degli studi di Roma Foro Italico (Other)
32
1
2
13.5
2.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Device: Cortico-cortical stimulation plus robot-assisted therapy
  • Device: Sham cortico-cortical stimulation plus robot-assisted therapy
N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomised Clinical trialRandomised Clinical trial
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Cortico-cortical Stimulation and Robot-assisted Therapy a New Approach of Upper Limb Functional Recovery After Stroke
Anticipated Study Start Date :
Aug 16, 2022
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Change in the Fugl-Meyer Assessment Scale for Upper Extremity (FMA-UE) [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.

Secondary Outcome Measures

  1. Change in the Box and Block Test [baseline; 3weeks (end of treatment); 7weeks (follow-up)]

    Clinical test of motor function of upper limb after stroke.

  2. Change in the Modified Ashworth Scale [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.

  3. Change in the whole-hand force [baseline; 3weeks (end of treatment); 7weeks (follow-up)]

    Clinical test performed with a manual dynamometer

  4. Change in the functional movements of upper limb [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.

  5. Change in the cortical excitability [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 .

  6. Change in the cortical oscillations [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.

  7. Change in the cortical connectivity [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Santa Lucia Foundation Rome Italy 00179

Sponsors and Collaborators

  • I.R.C.C.S. Fondazione Santa Lucia
  • Università degli studi di Roma Foro Italico

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
I.R.C.C.S. Fondazione Santa Lucia
ClinicalTrials.gov Identifier:
NCT05478434
Other Study ID Numbers:
  • PROG.910
First Posted:
Jul 28, 2022
Last Update Posted:
Jul 28, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by I.R.C.C.S. Fondazione Santa Lucia
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 28, 2022