Non Invasive Vagus Nerve Stimulation in Cerebral Palsy (BOOSTTVNS)

NCT06372028 | Not Yet Recruiting

• 1 other identifier: 944/A
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The present study aims to assess, through a randomized controlled trial (RCT), the efficacy of transcutaneous Vagus Nerve Stimulation (tVNS) in enhancing the functional changes due to an intensive motor training in children and adolescents with Cerebral Palsy (CP). Particularly, in two different groups active or sham tVNS will be paired with the Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) and we will assess the effects on the upper limbs motor ability and daily functioning in 6 to 17 years old patients with CP having mild-to moderate upper limb deficits. The investigators hypothesized that, thanks to the intensive bimanual training, both the active and the sham group will improve in motor functioning. However, taking into account that tVNS has the potential to facilitate in a bottom-up way neural plasticity, particularly in chronic disease conditions, the investigators hypothesized that active tVNS might improve in a greater and more lasting extent than sham tVNS the motor functioning. Moreover, as suggested by previous studies investigating the effect of non-invasive brain stimulation (NIBS) in paediatric population, the investigators expected that the treatment will be safe and well tolerated. Such a result would encourage the use of NIBS to boost the rehabilitative training of motor abilities in children and adolescents with CP.

Conditions

Cerebral Palsy

Keywords

transcutaneous Vagus Nerve Stimulation; intensive bimanual training; neurorehabilitation; non invasive brain stimulation; upper limb motor deficit

Outcome Measures

Primary Outcomes (3)

• Assisting Hand Assessment (AHA)

  This scale enables to quantify the assistance provided by the more affected hand to the less affected hand during bimanual activities. This observation-based, criterion-referenced assessment highlights a person's typical performance, emphasizing practical functionality over maximal capacity, and serves as a reliable measure of change over time. The scale comprised 20 items, scored on a 4-point Likert scale, from 1 to 4. The total score indicates how well the more affected hand is used as an assisting hand. A score of 20 means poor performance (the hand is not used as an assisting hand); a score of 80 means that the hand is used effectively. The results are converted for each of the three scales to logits by a Rasch analysis, on a 0-to-100 scale (with higher scores suggesting better use).

  1-2 days before the start of training (t0), 1-2 days after the end of the training (t1), three months after the end of the training (t2)

• Box and Block Test (BBT)

  This test is designed to measure manual dexterity. It is quick, simple, and cost-effective. It involves a box with a partition in the middle placed on a table, with a total of 150 blocks on one side of the partition. The score of the test is given by the number of blocks transported within a minute. Higher values suggest better performance. The BBT provides a reliable and objective measurement of manual dexterity, making it valuable for evaluating functional outcomes and monitoring progress in rehabilitation programs over a short period of time.

  1-2 days before the start of training (t0), 1-2 days after the end of the training (t1), three months after the end of the training (t2)

• Visuomotor task

  The visuomotor task is an ad hoc computer based task. It involves a mouse click-and-drag operation where an object appears at the center of the screen. The objective is to drag and drop the object to the location indicated by a previously presented arrow, pointing towards a target object within a configuration of objects. Participants are required to focus on the arrow's direction, swiftly and accurately moving the central object to its designated target location. This task enables the measurement of movement time (in milliseconds; consisting in the time necessary to move the object in the target position); precision error (calculated as the distance, in pixels, between the drop position of the object and the actual target position); the proportion of overtime errors (the percentage of trials in which responses are too slow). Smaller values of Movement time, Precision error and overtime errors will suggest better performance.

  1-2 days before the start of training (t0), 1-2 days after the end of the training (t1), three months after the end of the training (t2)

Secondary Outcomes (6)

• Canadian Occupational Performance Measure (COPM)

  1-2 days before the start of training (t0), 1-2 days after the end of the training (t1), three months after the end of the training (t2)

• Children's Hand-UseExperienceQuestionnaire (CHEQ)

  1-2 days before the start of training (t0), 1-2 days after the end of the training (t1), three months after the end of the training (t2)

• Melbourne Assessment 2 (MA2)

  1-2 days before the start of training (t0), 1-2 days after the end of the training (t1), three months after the end of the training (t2)

• Gross Motor Function Measure (GMFM-66)

  1-2 days before the start of training (t0), 1-2 days after the end of the training (t1), three months after the end of the training (t2)

• Vineland Adaptive Behavior Scale Version 2 (VABS II)

  1-2 days before the start of training (t0), three months after the end of the training (t2)

Other Outcomes (6)

• Heart rate (HR).

  in the first 2 minutes, after 20 minutes of stimulation, after 75 minutes of stimulation

• Oxygen saturation (SPO2).

  in the first 2 minutes, after 20 minutes of stimulation, after 75 minutes of stimulation

• Tolerability of the stimulation

  immediately after every stimulation sessions of the 10-days training

Study Arms (2)

Active tVNS combined with the training

EXPERIMENTAL

The active stimulation will be applied through an active electrode placed on the cymba conchae (the auricular branches of the vagus nerve) of the left ear. The intensity will be set based on the individual perceptual threshold, below the perception of pain. The intensity of the stimulation will be gradually increased in order to reach the intensity of stimulation with a ramping-up phase of 30 secs. The tVNS will be applied for the first 75 minutes of the training, every day of the treatment. Before, 20 minutes and 75 minutes after the start of the stimulation SpO2 and HR will be checked. At the end of the stimulation session participants will be asked to report the sensations and possible side effects occurring during tVNS and to rate their feeling on several visual analogue scales and Likert scales. The intensive bimanual training will be administered by following the procedure described in the Detailed Description session, as for the Sham tVNS combined with the training arm.

Device: transcutaneous vagus nerve stimulation (tVNS)

Sham tVNS combined with the training

SHAM COMPARATOR

The sham stimulation will be applied through an active electrode placed on lobe of the left ear that is free of cutaneous vagal innervations. The stimulation intensity will be set based on the individual perceptual threshold, below the perception of pain. The intensity of the stimulation will be gradually increased in order to reach the intensity of stimulation with a ramping-up phase of 30 secs. The tVNS will be applied for the first 75 minutes of the training, every day of the treatment. Before, 20 minutes and 75 minutes after the start of the stimulation SpO2 and HR will be checked. At the end of the stimulation session participants will be asked to report the sensations and possible side effects occurring during tVNS and to rate their feeling on several visual analogue scales and Likert scales. The intensive bimanual training will be administered by following the procedure described in the Detailed Description session, as for the Active tVNS combined with the training arm.

Device: transcutaneous vagus nerve stimulation (tVNS)

Interventions

transcutaneous vagus nerve stimulation (tVNS) DEVICE

tVNS allows the non-invasive stimulation of the Vagus Nerve by delivering electrical pulses to the sensory afferent fibers of the auricular, thick-myelinated, branch of the vagus nerve in the outer ear. TVNS seems to engage the same neural pathways of invasive VNS methods and may provide a novel, bottom-up NIBS method to enhance gamma-aminobutyric acid and Noradrenaline levels, which play a pivotal role in brain plasticity. The stimulation will be performed by using a Conformite Europeenne (CE) marked tVNS device tVNS®E (tVNS, technologies Gesellschaft mit beschränkter Haftung (GMBH), Erlangen, Germany). It consists in a programmable stimulation unit connected to two titan ear electrodes that are mounted on a gel frame, allowing to generate and transfer electric impulses from the stimulation unit to the surface of the skin, where the electrodes are applied.

Active tVNS combined with the training; Sham tVNS combined with the training

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• clinical signs of unilateral or bilateral upper limb deficits (with a difference at least of 25% between more affected and less affected hand at Box and Block test);
• Magnetic Resonance Imaging (MRI) confirmed diagnosis according to Surveillance of Cerebral Palsy (SCPE) criteria;
• Manual Ability Classification System (MACS) level I,II,III;
• Gross Motor Function Classification System (GMFCS) level I,II,III;
• Visual Function Classification System (VFCS) I-II-III;
• Intelligence quotient (IQ) \> 50.

You may not qualify if:

• presence of cochlear implant, cardiac pacemaker, ventriculoperitoneal shunt, neuro-stimulators, clips, fragments or metal splinters in the brain or skull except for titanium;
• treatments for spasticity or functional surgery of the upper limb in the previous 6 months or planned during the duration of the study;
• uncontrolled epileptic seizure in the last 2 years.

Sponsors & Collaborators

• IRCCS Eugenio Medea: lead
• IRCCS National Neurological Institute "C. Mondino" Foundation: collaborator
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: collaborator

Study Sites (1)

Scientific Institute, IRCCS E. Medea

Bosisio Parini, Lecco, 23842, Italy

Location

Related Publications (2)

• Vacchini V, Brafa B, Nicotra R, Capelli E, Signorini S, Gasparroni V, Michelutti A, Oldrati V, Galli J, Urgesi C, Cattaneo Z, Fazzi EM, Borgatti R, Finisguerra A, Orcesi S; Boost Working Group. Improving neuroplasticity and Quality of Life in children with Cerebral Palsy: a customized intensive motor training protocol integrating the HABIT-ILE approach. Front Rehabil Sci. 2025 Oct 13;6:1613103. doi: 10.3389/fresc.2025.1613103. eCollection 2025.

  PMID: 41158535 DERIVED

• Oldrati V, Gasparroni V, Michelutti A, Ciricugno A, Borgatti R, Orcesi S, Fazzi E, Morandi A, Galli J, Piccinini L, Maghini C, Arioli M, Cattaneo Z, Urgesi C, Finisguerra A. Pairing transcutaneous vagus nerve stimulation with an intensive bimanual training in children and adolescents with cerebral palsy: study protocol of a randomized sham-controlled trial. Front Neurol. 2024 Aug 16;15:1441128. doi: 10.3389/fneur.2024.1441128. eCollection 2024.

  PMID: 39220734 DERIVED

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

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

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 17, 2024
• Study Start: April 15, 2024
• Primary Completion: March 14, 2026
• Study Completion (Estimated): May 14, 2026
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Before data analyses, for ten years.
• Access Criteria: all

Locations

IT (1)