Trial Title:
Prehabilitation, Rehabilitation and Comprehensive Approach to the Sequelae of Brain Tumors
NCT ID:
NCT05844605
Condition:
Brain Tumor
Conditions: Official terms:
Brain Neoplasms
Conditions: Keywords:
brain tumour
prehabilitation
neuromodulation
motor training
cognitive training
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Pilot single-cohort feasibility open-label trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Non-invasive neuromodulation (TMS and/or tDCS)
Description:
Non-invasive neuromodulation (TMS and/or tDCS) coupled with intensive behavioural
training (neurorehabilitation and/or cognitive rehabilitation)
Arm group label:
Prehabilitation
Summary:
The goal of the present pilot single-cohort feasibility trial is to investigate the
feasibility and understand potential mechanisms of efficacy for Neuromodulation-Induced
Cortical Prehabilitation (NICP) in adults with brain tumours and eligible for
neurosurgery.
The main questions it aims to answer are:
- is the intervention feasible, in terms of adherence, retention, safety and patient's
satisfaction;
- what are the mechanisms of neuroplasticity primed by NICP
Participants will undergo a prehabilitation protocol, consisting of daily sessions
(total: 10-20 sessions) structured as follows:
- Intervention 1: non-invasive neuromodulation (TMS/tDCS).
- Intervention 2: motor and/or cognitive training, during or immediately after
non-invasive neuromodulation, for about 60 minutes.
The timeline is structured as follows:
T1: baseline (before NICP) T2-T3: NICP period T4: after NICP T5: surgery T6: after
surgery
Clinical, neuroimaging and neurophysiology assessments will be performed before NICP
(T1), after NICP (T4), and after neurosurgery (T6). Feasibility outcomes will be
determined during NICP protocol (T2-T3).
The objective of the proposed intervention is to progressively reduce the functional
relevance of eloquent areas, which are healthy brain areas close with the tumour and thus
exposed to the risk of being lesioned during surgery. In fact, previous studies have
shown that temporary inhibition of eloquent areas (by neuromodulation) coupled with
intensive motor/cognitive training promoted the activation of alternative brain
resources, with a shift of functional activity from eloquent areas to areas functionally
related, but anatomically distant from the tumour.
By moving the activation of key motor/cognitive functions away from the tumour, the risk
of postoperative functional sequelae will be reduced; which in turn will falicitate a
more radical tumour excision by the neurosurgeon.
Detailed description:
Neuromodulation-Induced Cortical Prehabilitation (NICP) is a relatively new approach in
the neurosurgical field. It consists of priming neuroplastic changes before neurosurgery
for brain tumours, in order to improve surgical outcomes and, hopefully, long-term
survival and quality of life. The intervention comprises two elements:
1. Neuromodulation (like transcranial magnetic stimulation, TMS, and transcranial
direct current stimulation, tDCS). The goal of neuromodulation is to inhibit the
eloquent areas, defined as brain areas functionally active and close to the tumour.
2. Behavioural training (like motor training, cognitive training, or a combination).
The function trained corresponds with the function of the eloquent area targeted by
neuromodulation.
The two interventions are provided on a daily basis, and repeated over 10-20 consecutive
weekdays. Notably, after the inhibition of the eloquent area there is a temporal window
of about one hour, where intensive training of the same function requires the activation
of alternative areas/pathways. By consolidating this alternative activation over multiple
sessions, the outcome is a reduction in the functional relevance of eloquent areas, in
favour of alternative resources anatomically distant from the tumour.
Only few case reports have been published so far, with very positive results obtained by
means of invasive neuromodulation; the term 'invasive' means that a first neurosurgery
was required to implant electrodes over eloquent areas for intracranial electrical
stimulation, followed after few days/weeks by a second surgery for tumour removal.
Despite relevant neuroplastic changes, the problem with this approach has been the high
rate of adverse events occurred (infections, edema, pain, seizure) due to the
invasiveness of the procedures. Therefore, by using a non-invasive neuromodulation
approach, the goal of the present trial is to promote neuroplastic changes beneficial for
neurosurgery, while at the same time ensuring no serious adverse events.
Further details on neuromodulation. Investigators will apply the most appropriate
neuromodulation protocol, personalized based on whether to perform TMS and/or tDCS,
individual resting motor threshold (for TMS), and target determination (related to
eloquent areas).
Protocol for low frequency rTMS:
- intensity: 90% RMT;
- frequency: 1 Hertz;
- total number of pulses: 1600.
Protocol for tDCS:
- cathode: over eloquent areas
- anode: typically over areas that should be activated, as opposed to eloquent areas
Further details on upper limb prehabilitation training.
Within the 60 minutes immediately after neuromodulation, patients will perform an
intensive training of the same function of the eloquent area, which is now temporarily
inhibited. Intensity of the training will be continuously adjusted in terms of type,
difficulty and variability:
- Type: exercises specific for finger individuation (play the piano, typewriting),
finger coordination (dexterity, manipulation), arm reaching. In order to integrate
upper limb function with other motor-cognitive functions, dual task training will be
performed, both motor-cognitive (decision making, stroop task, motor sequence
learning etc.) and motor-motor (bimanual activites, arm and balance tasks, etc.);
- Difficulty: the intensity of the exercise will be set as to result 'difficult, yet
achievable' by the patient. This way it is ensured that the brain is under a stress
condition which, together with concurrent eloquent area inhibition, will promote and
consolidate the activation of alternative resources.
- Variability: varying systematically the type and difficulty of the training is
useful to keep the patient engaged and ensure that the end result will be a global
motor-cognitive training, instead of a monotonic improvement in a specific
performance.
Further details on Prehabilitation for language and cognitive training.
Language-cognitive training will follow the same rationale illustrated for motor
training. Soon after neuromodulation the patient will perform a computerized cognitive
training on a dedicated platform ("Guttmann NeuroPersonalTrainer"® (GNPT). Exercises will
be customized based on specific patient's deficits, and/or functions at risk of being
compromised after surgery. For instance, the neuropsychologist may vary settings such as
presentation speed, latency time or number of images, thus finely tuning several
difficulty levels. Regarding language, tasks will be planned and supervised in a
personalized way by a neuropsychologist, readjusting their planning if necessary.
Discontinuation, adherence, and permission for concomitant care.
The intervention will be discontinued in the following cases:
- participant's request;
- serious adverse events attributable to the intervention. Patients will be allowed to
continue any ongoing treatment. Formal training of motor-cognitive functions outside
the protocol will be discourage, as it may affect neuroplastic changes in an
unpredictable way.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- diagnosis of brain tumour requiring neurosurgery
- ability to undertake at least 10 sessions of prehabilitation protocol
- tumour location posing the patient at risk of developing post-operative neurological
deficits, for instance at the level of upper limb motor function and speech
production
- ability to understand the general purpose of the prehabilitation program and
understand simple instructions
- being willing to participate and sign the informed consent
- being able to sit unassisted for one hour.
Exclusion Criteria:
- any contraindication for magnetic resonance imaging or transcranial magnetic
stimulation
- unstable medical conditions
- musculoskeletal disorders that may significantly affect functional training
- pain, depression, fatigue that may significantly affect functional training
- history of alcohol/drug abuse
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut Guttmann
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Jose M Tormos Muñoz, PhD
Phone:
0034686940393
Email:
jmtormos@guttmann.com
Contact backup:
Last name:
Kilian A Abellaneda Perez, PhD
Phone:
0034628906400
Email:
kabellaneda@guttmann.com
Start date:
June 21, 2021
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Institut Guttmann
Agency class:
Other
Source:
Institut Guttmann
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05844605
https://www.guttmann.com/en/prehabilita-project
