Transcranial Alternating Current Stimulation in Cerebral Palsy (BOOSTTACS)

NCT ID: NCT06372041

Last Updated: 2024-04-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-15
• Study Completion Date: 2026-05-14

Brief Summary

The present study aims to assess, through a randomized controlled trial (RCT), the efficacy of transcranial alternating current stimulation (tACS) 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 tACS 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, in light of findings showing that tACS effectively improves motor learning, the investigators hypothesized that active tACS might improve in a greater and more lasting extent than sham tACS the motor functioning. Moreover, as suggested by previous studies investigating the effect of non-invasive brain stimulation (NIBS) in pediatric 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.

Detailed Description

This represents one of the two RCTs of the project "Bottom-up and tOp-down neuromOdulation of motor plaSTicity in cerebral palsy" (BOOST; FRRB 3438840).The study will be a randomized, sham controlled, pre-test/post-test study involving 44 children and adolescents with CP. Patients will be treated in pairs, with a matching of motor deficit severity, IQ, or age. Each pair will be randomly assigned to the active or to the sham tACS group, stratifying the pairs between the two groups based on motor deficit severity, IQ, or age. Both groups will undergo a bimanual training in an ecological and highly motivating environment during the application of the tACS. During the training, starting from a set of proposals the choice of the type of activities to be practiced in each session will be left to patients, boosting the motivational aspect of the training. This will also ensure an individualized and goal directed approach. The therapists will monitor and modify the activities within each pair to ensure that the intervention maintains the quality of the individualized intervention. The positions performed during bimanual tasks and the activities of daily living will be designed to systematically engage postural control of the trunk and lower limbs according to Habit-ILE protocol. The rehabilitation treatment will be carried out for 5 consecutive days for 3h/day for 2 weeks (30 hours of intervention overall). Children and adolescents will be assessed before the start of treatment (T0), immediately after the end of intensive treatment (T1) and three months after the end (T2). The overall RCT will be structured as follows. In the first session prior the beginning of the training (t0), the RCT will include the administration of all clinical assessment measures and the patients will be asked to perform for 10 minutes an ad-hoc computer based Visuomotor task (please refer to the outcome sessions for more detailed description). Cortical rhythms will be recorded by electroencephalogram (EEG) both before (during rest) and during the execution of the Visuomotor task. Analysis of the resting-state EEG will be conducted to derive the Individualized Gamma Frequency (IGF), which will be matched to each patient's specific stimulation frequency delivered through tACS during the training. Patients will undergo the 10 days treatment. For each training day, the treatment will last three hours. During the first 20 minutes of treatment the active or sham tACS (according to the group allocation) will be delivered. Before starting and 20 minutes after the end of the stimulation the vital parameters will be checked. After the end of the stimulation, patients will be also asked to rate the sensations experienced during the stimulation through Visual Analogue Scales and through child-friendly Likert scales. Then, they will continue the training for the remaining session time without stimulation. Soon after the end of all the training sessions, patients will carry the t1 evaluation. As for the t0 session, this session will include the administration of the clinical assessment measures and execution for 10 minutes of the Visuomotor task. Three months after the end of the training (t2) the follow up assessment will be conducted, following the same exact procedure of t0.

Primary outcomes will include the following clinical measures: the Assisting Hand Assessment (AHA), the Box and Block Test (BBT) and the performance at the Visuomotor task. Secondary outcome will include the scores at the following tests: the Children's Hand Experience Questionnaire (CHEQ), the Canadian Occupational Performance Measure (COPM), the Gross Motor Function Measure (GMFM-66), the Melbourne Assessment-2 (MA2) scale, the Vineland Adaptive Behavior Scale Version 2 (VABS 2), the Pediatric Quality of Life Inventory (PEDS-QL), and the cortical rhythms registered via EEG at rest and during the Visuomotor task. Vital parameters (the oxygen saturation (SPO2) and the Heart Rate (HR)), and the scores at the questionnaires assessing stimulation- induced sensations will be also checked to assess the safety and the tolerability of the stimulation. Lastly, the feasibility and the acceptability of the training will be assessed by considering, respectively, the number of patients completing the training/the number of sessions for each patient and the response to ad hoc questionnaires for the patients and their guardians.

All primary and secondary outcomes will be collected at each time point, except for the PedsQL and VABS-II, that will be administered only at T0 and T2. Furthermore, vital parameters and the questionnaires assessing stimulation-induced sensations will be examined during each stimulation session. The acceptability questionnaires will be administered only after the end of the training (t1).

The patients and their guardians, the personnel responsible for conducting the bimanual training and analysing clinical data will be kept blind to the group allocation. Instead, the coordinator of the study, the staff who will apply the tACS will be "not blind". With respect to the clinical assessment, whenever possible the staff administering and scoring the scales will be blinded to group allocation. Questionnaire scores and neuropsychological tests will not contain personal information about the subjects, who will be identified by an alphanumeric code. All records that contain names or other personal identifiers, such as informed consent forms, will be stored separately from study records identified by code number. In order to uphold the overall quality of the clinical trial, instances of code breaks should be limited to exceptional circumstances, where knowledge of the actual treatment is deemed absolutely necessary for the ongoing management of the patient.

The intensive treatment will take place at IRCCS E. Medea "Associazione La Nostra Famiglia" in Bosisio Parini (Lecco), at Fondazione Mondino IRCCS (Pavia) and at ASST Ospedali Civili di Brescia.

This trial is supported by Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia), project FRRB 3438840 BOOST "Bottom-up and tOp-down neuromOdulation of motor plaSTicity in cerebral palsy".

Conditions

Cerebral Palsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active tACS combined with the training

The tACS will be applied for the first 20 minutes of the training, every day of the treatment. Before and the after of the stimulation, SpO2 and HR will be checked. After the stimulation participants will be asked to rate the sensations and possible side effects occurring during tACS. The intensive bimanual training will be administered by following the procedure described in the Detailed Description session, as for the Sham tACS combined with the training arm.

Group Type: EXPERIMENTAL

transcranial Alternating Current Stimulation

Intervention Type: DEVICE

tACS will be performed by using a Conformite Europeenne (CE) marked stimulator device (Starstim ®, Neuroelectrics, Barcelona, Spain). By applying alternating current at the gamma frequency band (range 30-80), known to be associated to motor performance, tACS can entrain or synchronize neural oscillations in the targeted brain regions. By modulating cortical excitability of the cerebellum, a region strongly involved in motor learning and coordination, tACS is expected to influence the strength and coordination of motor responses elicited during the training. tACS will be delivered through two saline-soaked surface sponge electrodes (dimension: 25cm2 each), one placed over F3 (left frontal region) and the other over the right cerebellar hemisphere. The intensity will be set to 1mA, and this value will be gradually reached with a ramping-up phase of 30 secs. The frequency of the stimulation will match the IGF identified during the EEG recording performed at rest.

Sham tACS combined with the training

The sham-tACS will be applied for the first 20 minutes of the training, every day of the treatment. However, in this condition, after the initial 30 seconds of ramp-up phase of the current, the stimulation will be switched off. This procedure allows participants to feel the characteristic tingling sensations in the vicinity of the electrodes for a brief period of time, which enhanced the plausibility of the sham condition.Before and the after of the stimulation, SpO2 and HR will be checked. After 20 minutes from setting-up the stimulation, participants will be asked to report the sensations and possible side effects occurring during tACS 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 tACS combined with the training arm.

Group Type: SHAM_COMPARATOR

transcranial Alternating Current Stimulation

Intervention Type: DEVICE

tACS will be performed by using a Conformite Europeenne (CE) marked stimulator device (Starstim ®, Neuroelectrics, Barcelona, Spain). By applying alternating current at the gamma frequency band (range 30-80), known to be associated to motor performance, tACS can entrain or synchronize neural oscillations in the targeted brain regions. By modulating cortical excitability of the cerebellum, a region strongly involved in motor learning and coordination, tACS is expected to influence the strength and coordination of motor responses elicited during the training. tACS will be delivered through two saline-soaked surface sponge electrodes (dimension: 25cm2 each), one placed over F3 (left frontal region) and the other over the right cerebellar hemisphere. The intensity will be set to 1mA, and this value will be gradually reached with a ramping-up phase of 30 secs. The frequency of the stimulation will match the IGF identified during the EEG recording performed at rest.

Interventions

transcranial Alternating Current Stimulation

tACS will be performed by using a Conformite Europeenne (CE) marked stimulator device (Starstim ®, Neuroelectrics, Barcelona, Spain). By applying alternating current at the gamma frequency band (range 30-80), known to be associated to motor performance, tACS can entrain or synchronize neural oscillations in the targeted brain regions. By modulating cortical excitability of the cerebellum, a region strongly involved in motor learning and coordination, tACS is expected to influence the strength and coordination of motor responses elicited during the training. tACS will be delivered through two saline-soaked surface sponge electrodes (dimension: 25cm2 each), one placed over F3 (left frontal region) and the other over the right cerebellar hemisphere. The intensity will be set to 1mA, and this value will be gradually reached with a ramping-up phase of 30 secs. The frequency of the stimulation will match the IGF identified during the EEG recording performed at rest.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS National Neurological Institute "C. Mondino" Foundation

OTHER

Sponsor Role: collaborator

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

OTHER

Sponsor Role: collaborator

IRCCS Eugenio Medea

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Scientific Institute, IRCCS E. Medea

Bosisio Parini, Lecco, Italy

Countries

Italy

Facility Contacts

Alessandra Finisguerra

Role: primary

alessandra.finisguerra@lanostrafamiglia.it

+39031877652

Cosimo Urgesi

Role: backup

cosimo.urgesi@lanostrafamiglia.it

+39031877652

References

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.

Reference Type: DERIVED

PMID: 41158535 (View on PubMed)

Oldrati V, Ciricugno A, Borgatti R, Orcesi S, Fazzi E, Galli J, Gasparroni V, Piccinini L, Maghini C, Cattaneo Z, Arioli M, Urgesi C, Finisguerra A. tACS-combined motor training for the rehabilitation of the upper limb in children and adolescents with cerebral palsy: A randomized, sham-controlled trial protocol. PLoS One. 2025 Sep 3;20(9):e0331360. doi: 10.1371/journal.pone.0331360. eCollection 2025.

Reference Type: DERIVED

PMID: 40901773 (View on PubMed)

Other Identifiers

944/B

Identifier Type: -

Identifier Source: org_study_id