Clinical trial NCT05370274: Using Cranial Nerve Non-invasive Neuromodulation to Improve Pain and Upper Extremity Function After a Stroke
Official title: Cranial Nerve Non-invasive Neuromodulation to Improve Pain and Upper Extremity Function in Individuals in the Chronic Phase of Stroke: a Pilot Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Keywords: Exercise
Upper limb
Motor recovery
Pain
Cranial nerve non-invasive neuromodulation
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
First posted: 2022-05-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: The study model is a pre/post intervention pilot study.
Primary purpose: TREATMENT

Brief summary: Following a stroke, individuals experience pain in the affected upper limb (UL) and residual weakness in the UL, which impacts their quality of life and performance of activities of daily living. To overcome these deficits, exercises are a key element to any rehabilitation program and are based on the reorganization capacity of the central nervous system (called neuroplasticity). To optimize the beneficial effects of exercises and potentiate neuroplasticity, non-invasive brain stimulation devices (NIBS) are increasingly used as a complementary therapy post stroke. Among NIBS, a new technique, called cranial nerve non-invasive neuromodulation (CN-NINM), is making its way into stroke rehabilitation since, unlike other NIBS such as tDCS, it allows the generation of a direct flow of neuronal impulses via the stimulation of the tongue. The goal of this project is therefore to investigate CN-NINM to document its feasibility and explore its efficacy at improving motor recovery and reduce pain at the affected UL in chronic stroke patients (\> 6 months). CN-NINM will be applied for 20 minutes during each exercise session of the UL (3X/week, 4 weeks). Feasibility data will comprise adherence to CN-NINM, drop out rate and adverse events and UL motor recovery and pain will be assessed before and after the exercise program. At the end of this study, it is expected that it will be feasible to use CN-NINM as an intervention in combination with the exercise program and that it will result in improved motor function and reduced pain in affected UL.

Detailed description: Following a stroke, survivors experience pain in the affected upper limb (UL) and residual weakness in the UL, which impacts their quality of life and performance of activities of daily living. Exercises is a key element of any rehabilitation program and is based on the capacity of reorganization of the central nervous system (called neuroplasticity) to allow overcoming stroke deficits. In addition, it is now recognized that in the chronic phase of a stroke, motor and functional gains are still possible following various training programs, such as a strength training program. To optimize the beneficial effects of exercise and potentiate neuroplasticity, non-invasive brain stimulation (NIBS) devices are increasingly used as a complementary therapy. Among NIBS, the most widely used technique is transcranial direct current stimulation (tDCS) that modulates cortical excitability and allows for clinical and functional gains, including recovering in UL motor function and pain. However, over 50% of individuals do not respond as expected to the combination of tDCS and rehabilitation exercises. This can be due to anatomical variability between individuals and electrical current shunting. Thus, to bypass these constraints, a new technique, called cranial nerve non-invasive neuromodulation (CN-NINM), is entering stroke rehabilitation. Unlike other NIBS such as tDCS, it generates a direct flow of neural impulses via tongue stimulation. Studies have shown that priming the motor cortex with CN-NINM during a training program can promote improved balance and gait and increased activation of the motor cortex. Until now, no studies have examined the use of CN-NINM for improving UL function and pain.

Goals: 1) To assess the feasibility of using CN-NINM in chronic stroke survivors; 2) To explore the effectiveness of CN-NINM in improving motor function and reducing pain of the affected upper limb in chronic stroke survivors.

Methods: In this feasibility pilot pre/post intervention study, 12 adults at the chronic phase of a stroke (\>6 months) will be recruited. Sociodemographic and stroke-related variables (e.g., age, time since stroke) will be collected to confirm participant eligibility. Prior to training, participants will undergo a clinical evaluation of their affected UL as well as an evaluation of simulated pain at the affected UL. For the latter, the effect of CN-NINM on pain will be evaluated using a tonic thermal experimental pain paradigm. For this, a thermode (hot plate) will be applied to the forearm of the participants before and after a single 20-minute application of CN-NINM. On each occasion, thermal nociceptive stimuli will be induced for 2 minutes on the participants' forearm using the thermode. Although the temperature remains constant for the entire 2 minutes, the participant will be informed that the temperature may increase, decrease, or remain stable during the procedure. The participant will then, at all times, evaluate the intensity of the pain with a visual analogue scale connected to a computer (CoVAS: visual analogue scale from 0 to 100). Afterwards, the participants will take part in a 4-week training program of their affected UL (3X/week, 60-minute duration). During each training session, the CN-NINM will be applied for 20 minutes at an intensity tailored to each participant comfort.

Eligibility criteria: Inclusion Criteria:

1. Be ≥18 years old;
2. Have had a single supratentorial stroke;
3. Be in a chronic stroke phase (\>6 months);
4. Present motor recovery in the upper limb (UL) (Fugl-Meyer Stroke Assessment \[FMA\] score ≥20/66);
5. Have completed any rehabilitation treatment.

Exclusion Criteria:

1. A significant spasticity at the affected upper limb (score \> 3 on the modified Ashworth scale);
2. A major sensory deficit at the affected upper limb (a score ≤25/34 on the Nottingham Sensory Assessment and a score \<6 on the evaluation of the vibration threshold);
3. A presence of hemineglect (score ≥±0. 083 on the Line Cancellation test);
4. An apraxia (score \>2.5 on the Alexander Test);
5. The presence of a neurological disorder other than a stroke;
6. Concomitant orthopaedic problem at the affected UL;
7. Cognitive impairment (Mini-Cog score \<2/5) and
8. Any contraindication to CN-NINM.

Primary outcomes:
measure: Recruitment rate for the project
timeFrame: Information will be assessed at the end of the recruitment period, at week 28
measure: Refusal to participate and the reasons
timeFrame: Information will be assessed throughout the project recruitment period (average of 7 months)
measure: Dropped out rate of the project in percent and the reasons
timeFrame: Information will be assessed through project completion, an average of 9 months
measure: Adherence to the intervention (training program and CN-NINM) in percent
timeFrame: Information will be assessed through study completion, an average of 9 months
measure: Number of participants with CN-NINM-related adverse events as assessed by a questionnaire
timeFrame: Information will be be assessed through study completion, an average of 9 months
Secondary outcomes:
measure: Change in pain intensity on the CoVAS
timeFrame: The assessments will be done at the baseline and just after the 20 minutes of application of the CN-NINM.
measure: Change in UL functional performance on the Wolf Motor Function Test
timeFrame: The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.
measure: Change in UL motor function on the Fugl-Meyer Stroke Assessment Scale
timeFrame: The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.
measure: Change in affected grip strength on the JAMAR dynamometer
timeFrame: The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.
measure: Change in manual dexterity on the Box and Block test
timeFrame: The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.
measure: Change in participants' subjective real life functional UL performance on the Motor Activity Log
timeFrame: The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre de recherche sur le vieillissement
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Marie-Hélène Milot, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Université de Sherbrooke
name: Guillaume Léonard, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: