Clinical trial NCT06396715: Optimal Therapeutic Dose of tDCS for Functional Upper Limb Recovery in People With Stroke
Official title: Optimal Therapeutic Dose of Transcranial Direct Current Stimulation for Functional Upper Limb Recovery in People With Stroke: Multicenter Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stroke
Neurologic Deficits
Keywords: Stroke
Transcranial direct current stimulation
Upper limb
Occupational Therapy
Lead sponsor: University of Chile
Sponsor class: OTHER
Collaborators: name: Agencia Nacional de Investigación y Desarrollo
First posted: 2024-05-02
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This methodological design is carried out following the guidelines of the CONSORT 2010 guidelines for clinical trials.

Study type and design: a two-arm, multicenter, double-blind randomized clinical trial (RCT) is proposed.

Population: adults with a diagnosis of subacute unihemispheric stroke with motor and functional deficit of the upper limb who attend the Hospital Clínico de la Universidad de Chile (HCUCH) and the Hospital San José (HSJ).
Primary purpose: TREATMENT

Brief summary: Stroke is one of the main causes of disability worldwide. The main disability after a stroke is hemiparesis of an Upper Limb (UL), with a prevalence of 70%. Although conventional UL therapies achieve good recovery, their effectiveness is still limited since only 5 to 20% of patients manage to completely recover. This has led to the use of therapies in a combined manner in order to achieve greater benefit. Due to its effects on brain neuroplasticity processes, transcranial direct current stimulation (tDCS), a type of non-invasive brain stimulation, has begun to be used as a complement to standard UL therapies, including combined with Constraint Induced Movement Therapy, whether original or modified (CIMT-mCIMT), with which it shares neurological principles, with evidence of its benefits.

In patients with mild and moderate stroke, tDCS has been used with the aim of reestablishing the altered brain balance by reducing the hyperactivity of the unaffected hemisphere and/or activating the affected hemisphere. A recent meta-analysis mentions that tDCS plus other therapies improve the function of the UL. However, the high heterogeneity of the protocols does not allow us to know the optimal dose, which, in turn, makes decision making in clinical practice difficult. This makes it apropos to develop studies that define therapeutic doses. This would contribute to clinical guidelines and allow to optimize public resources in rehabilitation.

The present study aims to compare the evolution of functional recovery of the UL in people with subacute stroke who attend the Hospital Clínico de la Universidad de Chile and the Hospital San José, after receiving bi-hemispheric tDCS, administered through a protocol of 18 thirty-minute sessions (experimental group) versus a protocol of 18 twenty-minute sessions (active comparator group). The hypothesis is that the experimental group obtains at least 5% more functional recovery compared to the active comparator group. One of the secondary objectives is to identify in which session the recovery plateau is achieved. A randomized, double-blind clinical trial is proposed, where patients will be assigned either to the experimental or active comparator group and both will receive mCIMT as standard therapy. Clinical and socio-demographic information will be gathered and patients will be evaluated with UL motor and functional recovery scales, as well as an evaluation of independence in basic Activities of Daily Living (ADL), among others.

Detailed description: Motor deficit and disability of the upper extremity (US) continues to be the most common sequelae in these patients, which has a significant impact on daily activities. It reduces independence and the probability of returning to work, among others. Although there is a high number of treatments with evidence, patients continue to have sequelae deficits. In addition to this, the high heterogeneity of the protocols makes it difficult to select the best alternative. Therefore, when deciding to use a treatment one of the biggest questions is to determine which combination of therapies and which dose is the most effective.

In the clinical trial carried out by our research team and published in 2022, it was demonstrated that the combination of rehabilitation strategies such as modified Constraint Induced Movement Therapy (mCIMT) and Transcranial Direct Current Stimulation (tDCS), generate significant results in motor and functional recovery of Ul in patients with acute and subacute stroke who are hospitalized. However, there is still no clarity in the optimal (effective and efficient) protocol and dose for subacute patients undergoing outpatient therapy. This is why our proposal aims to answer the pending questions through a randomized clinical trial that includes patients in the subacute stage who have been discharged from the hospital. Furthermore, the optimal dose (stimulation time and number of sessions) would be defined which would allow clear, updated, and accurate evidence to be generated in these patients.

ASSUMPTIONS

* The literature suggests that the best results of UL recovery, in protocols that include tDCS, are obtained with a moderate amount of total number of sessions (comprising between 15-24 sessions), but our local RCT showed results in 7 sessions.
* A very long therapy schedule is uncomfortable for the patient and caregiver and not very feasible to apply in our public health system, which is why the investigators propose an intermediate duration of 18 sessions.

It is reasonable to think that functional recovery tends to stabilize over time and that in a duration of 18 sessions could demonstrate the plateau.

HYPOTHESIS People with subacute stroke and moderate motor deficit of the upper limb who attend outpatient therapy and receive 18 sessions of 30 minutes of Bi-hemispheric Transcranial Direct Current Stimulation obtain at least 5% more functional recovery of the upper limb compared to those people who receive 18 sessions of 20 minutes of stimulation.

GENERAL OBJECTIVE Compare the evolution of functional recovery of the upper limb in people with subacute stroke who attend the Clinical Hospital of the University of Chile and the San José Hospital, after receiving bi-hemispheric transcranial stimulation by direct current, administered through a protocol of 18 30-minute sessions versus a protocol of 18 20-minute sessions.

METHODOLOGY AND PROCEDURES This methodological design is carried out following the guidelines of the CONSORT 2010 guidelines for clinical trials.

Study type and design: a two-arm, multicenter, double-blind randomized clinical trial (RCT) is proposed.

Population: adults with a diagnosis of subacute unihemispheric stroke with motor and functional deficit of the upper limb who attend the Hospital Clínico de la Universidad de Chile (HCUCH) and the Hospital San José (HSJ).

Interventions. Patients will be randomized to one of the following treatment groups: Experimental Group (30 minutes of bi-hemispheric tDCS combined with mCIMT for 18 sessions) or Active comparator Group (20 minutes of bi-hemispheric tDCS combined with mCIMT for 18 sessions).

General procedures.

* During the protocol, patients can continue participating in the usual interdisciplinary rehabilitation program in their hospitals, but it is suggested that they do not add therapies associated with the upper limb while participating in the protocol, as this may generate a risk of injury due to overuse.
* All patients will undergo neuromuscular taping on the deltoid of the paretic shoulder, with weekly changes, since it is part of the usual care at HCUCH.
* Patients should attend therapy wearing comfortable clothing (t-shirt and sweatshirt/shorts).
* Patients should be informed that, if they experience pain or discomfort while performing activities at home, practice should be temporarily suspended and the therapist notified. A transfer package is prepared, which will allow to monitor compliance with the CIMT protocol at home. Some activities of the transfer package include the delivery of videos with therapeutic material and the activities to be performed at home, as well as telephone follow-up to verify compliance with the completion of a check list-type guideline.

Eligibility criteria: Inclusion Criteria:

* Single event of ischemic or hemorrhagic unihemispheric stroke, cortical or subcortical.
* Brachial hemiparesis.
* Stroke evolution time greater than 7 days and equal to or less than 90 days.
* Subjects attend rehabilitation at the Hospital Clínico de la Universidad de Chile and Hospital San José.
* Age equal to or greater than 18 years.
* Present some level of UL motor activity: at least 20º of active wrist extension and 10º of finger extension.
* Have a caregiver and/or support network if necessary to attend outpatient therapies, as well as to supervise activities at home.
* Signing of informed consent by the patient.

Exclusion Criteria:

* Prior central stroke with motor sequelae.
* Present severe aphasia with a score ≥ 2 on the language item on the National Institutes of Health Stroke Scale evaluation.
* Severe cognitive impairment, with a score ≤ 15 points on the Mini-mental state examination.
* Present shoulder subluxation and/or pain \> 4 points on the visual numerical pain scale.
* History of epilepsy and/or use of antiepileptic drugs.
* Metal implants or pacemakers.
* Pregnancy.
* Any condition that, in the opinion of the doctor, impedes the correct performance of the treatment.

Primary outcomes:
measure: Functional recovery of upper extremity
timeFrame: 18 days, 3 and 6 months later
Secondary outcomes:
measure: Motor recovery of upper extremity
timeFrame: 18 days, 3 and 6 months later
measure: Independence in activities of daily living
timeFrame: 18 days, 3 and 6 months later
measure: Quality and quantity of movement of the upper limb
timeFrame: 18 days, 3 and 6 months later
measure: Health related quality of life
timeFrame: 18 days, 3 and 6 months later
measure: Satisfaction with intervention
timeFrame: At the end of the treatment
Other outcomes:
Locations:
Study officials:
affiliation: University of Chile
name: Maricel Garrido
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pollock A, Farmer SE, Brady MC, Langhorne P, Mead GE, Mehrholz J, van Wijck F. Interventions for improving upper limb function after stroke. Cochrane Database Syst Rev. 2014 Nov 12;2014(11):CD010820. doi: 10.1002/14651858.CD010820.pub2.
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citation: Liew SL, Santarnecchi E, Buch ER, Cohen LG. Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery. Front Hum Neurosci. 2014 Jun 27;8:378. doi: 10.3389/fnhum.2014.00378. eCollection 2014.
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