Motor Impairment, Motor Impairments, Stroke, Stroke, Ischemic, Stroke; Sequelae
Conditions
Keywords
Stroke, Vagus nerve, Vagus nerve stimulation, Transcutaneous vagus nerve stimulation, Rehabilitation
Brief summary
This study will evaluate the effects of transcutaneous vagus nerve stimulation in combination with physical rehabilitation on upper limb motor function of patients with stroke.
Detailed description
Stroke is a neurological condition caused by vascular problems such as cerebral infarction and/or intracerebral or subarachnoid hemorrhage(1). In 2019, more than 12 million strokes occurred worldwide, making it one of the leading causes of morbidity. Motor impairment is considered one of the main problems resulting from this condition(2). Recovery of motor function occurs spontaneously during the first months after stroke(3) as a result of brain plasticity processes in the sensory and motor systems(4). It is estimated that 50 to 75% of patients with stroke persist with significant motor sequelae limiting daily activities(5). Recently, Vagus Nerve Stimulation (VNS) has been proposed as an intervention that could have beneficial effects in the recovery of motor function in these patients, since it contributes to the generation of adaptive neuroplasticity and the activation of neuromodulators that reduce brain inflammation(6). VNS has mainly been administered by using implanted electrodes, but more recently, a non-invasive technique, known as transcutaneous VNS (cervical or auricular) has been proposed. VNS has traditionally required the implantation of an electrical pulse generator at the left subclavicular level, which is connected to electrodes in the left cervical branch of the vagus nerve(7). Its insertion is performed by a surgical procedure, which presents a higher risk of adverse events(8), the most frequent being dysphonia during stimulation, due to its proximity to the laryngeal nerve(9). On the other hand, transcutaneous VNS works through the placement of non-invasive electrodes on the neck or auricle for stimulation of the cervical or auricular branch of the vagus nerve respectively(7). Transcutaneous VNS has a lower risk of adverse events, is reversible and easy to implement(7). In addition, experimental evidence suggests that the effects of transcutaneous VNS on brain function are comparable to those obtained with VNS(8). This study will evaluate the effects of transcutaneous vagus nerve stimulation (tVNS) in combination with physical rehabilitation on upper limb motor function of patients with stroke. Thirty patients with ischemic stroke will be included in the study. Subjects will be randomized to tVNS + physical rehabilitation or sham stimulation + physical rehabilitation. Therapy sessions will be performed 3 times a week for six consecutive weeks. Efficacy will be evaluated by assessing the change in motor function of the upper limb, the next day and 30 days after the end of the intervention. The motor function of the upper limb will be assessed by means of the Fugl-Meyer scale score.
Interventions
DEVICETranscutaneous auricular vagus nerve stimulation + rehabilitation therapy
Transcutaneous auricular vagus nerve stimulation using INPULSE 3 times a week for six consecutive weeks. The stimulation parameters will be a frequency of 30Hz with a pulse width of 300 us and a stimulation time of 1.5 seconds for each respiratory cycle. The electrical current will be gradually increased to a maximum of 5 mA (0.25-mA increments) to allow adaptation to the stimulation until a comfortable tolerance level is achieved. Patients will receive physical rehabilitation therapy during stimulation, which will include reaching and grasping exercises, gross movements, turning objects, simulating specific tasks, inserting objects, opening and closing containers.
OTHERsham stimulation + rehabilitation therapy
Patients will receive physical rehabilitation therapy during placebo stimulation (No electrical stimulation), including reaching and grasping exercises, gross movements, turning objects, simulating specific tasks, inserting objects, opening and closing containers.
Sponsors
Ministerio de Ciencia Tecnología e Innovación - Minciencias
Fundación Cardiovascular de Colombia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
A double blinding will be performed. This information will be guaranteed to remain masked until after the analysis is performed.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age \>18 years and \<75 years * Unilateral supratentorial ischemic stroke that occurred at least 7 days but not more 30 days before enrollment. * Modified Rankin Scale between 0 and 1 before stroke * Contralesional UL motor impairment defined by NIHSS item 5 score ≥ 1 to ≤ 3. * Ability to provide written informed consent. * Hemodynamically stable patients. * Patients residing in the metropolitan area of Bucaramanga.
Exclusion criteria
* Significant cognitive or language impairment that would interfere with study participation or informed consent. This criterion will be defined by NIHSS item 1a-c score \> 2, item 9 score \> 1, item 11 score = 2. * Medical conditions that could interfere with study participation, for example ear infections or skin wounds. * Bradycardia (\< 50 bpm) or hypotension (\< 90/60 mmHg) * Significant pre-existing disability * History of stroke * History of cardiac arrhythmia * History of severe head trauma, brain surgery, deep brain stimulation, or brain injuries of other etiologies. * Pregnant or planning on becoming pregnant or breastfeeding during the study period. * Medical or mental instability (diagnosis of personality disorder, psychosis, or substance abuse) that would prevent subject from meeting protocol timeline. * Subjects who are currently in another clinical trial or plan to do so during the study period. * Patient receiving any therapy at study entry that would interfere with VNS (e.g., drugs that interfere with neurotransmitter mechanisms: anticholinergics, adrenergic blockers, etc.). * Prior injury to vagus nerve. * Any other implanted device such as a pacemaker or other neurostimulator; any other investigational device or drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motor function of the upper limb | 1 day and 30 days after the end of the intervention | Efficacy will be assessed by evaluating the change in motor function of the upper limb, the next day and 30 days after the end of the intervention. The motor function of the upper limb will be assessed by means of the Fugl-Meyer scale score. The motor function component ranges from 0 to 100, where higher scores indicate better motor recovery. |
| Arm and hand mobility Description: | 1 day and 30 days after the end of the intervention | Change in arm mobility the next day and 30 days after the end of the intervention. Arm and hand mobility will be assessed by the ARAT test. The maximum score on the ARAT is 57 points ( 0 to 57). A higher score indicates better arm function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital anxiety and depression | 1 day and 30 days after the end of the intervention | Change in anxiety and depression symptoms the next day and 30 days after the end of the intervention. The anxiety and depression symptoms will be assessed by means of the HADS scale score. Each subscale score ranges from 0 to 21, and higher scores indicate more severe anxiety and/or depressive symptoms. |
| Medical device safety | During the intervention period. | Adverse events associated with the stimulation, device and health attention are associated. It would be a measure of the number of events related or not related to the device. Each adverse event should be asses by ethical committee and medical team. |
Countries
Colombia
Contacts
Primary ContactNicolas Peña Novoa, Physiotherapist
Backup ContactSandra M Sanabria, Bacteriologist, PhD
Outcome results
None listed