Using Cranial Nerve Non-invasive Neuromodulation to Improve Pain and Upper Extremity Function After a Stroke

NCT ID: NCT05370274

Last Updated: 2024-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-27
• Study Completion Date: 2023-06-21

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.

Conditions

Stroke

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

strength training intervention

Strength training of the affected upper limb in chronic stroke survivors

Group Type: EXPERIMENTAL

Strength training intervention

Intervention Type: PROCEDURE

The strength training program will last 4 weeks (3 X/week, 60 minutes). Using dead weights, the 1RM (i.e. the maximal load that an individual can lift once) will be estimated by the 10RM in order to avoid tendino-muscular injuries and fatigue. The 10RM will be determined for the muscles playing a key role in the functional performance of the upper limb (the wrist extensors and the elbow and shoulder flexors). In addition, the grip muscles of the affected hand will be trained with a JAMAR® dynamometer. Training will start at 50% of 1RM and progress by 10% each week to reach 80% of 1RM by week 4. The same gradation of intensity will be applied to the grip muscles. The training will begin and end by a 5-minute warm-up and relaxation period comprising of active movements of the trained muscles.

Cranial nerve non-invasive neuromodulation (CN-NINM)

CN-NINM will be applied during each session of the strength training intervention

Group Type: EXPERIMENTAL

Cranial nerve non-invasive neuromodulation (CN-NINM)

Intervention Type: PROCEDURE

During each strength training session, the CN-NINM will be applied, with the help of a portable stimulator comprising a network of 18 electrodes, directly on the tongue of the participants for 20 minutes. The participants will hold the CN-NINM in place by pressing their tongue upwards. The CN-NINM will generate high-frequency pulses (50 μsec to 150 Hz), and the intensity of the stimulus will be set by each participant to a comfortable level of sensation, similar to the sensation in the mouth of a soft drink.

Interventions

Strength training intervention

The strength training program will last 4 weeks (3 X/week, 60 minutes). Using dead weights, the 1RM (i.e. the maximal load that an individual can lift once) will be estimated by the 10RM in order to avoid tendino-muscular injuries and fatigue. The 10RM will be determined for the muscles playing a key role in the functional performance of the upper limb (the wrist extensors and the elbow and shoulder flexors). In addition, the grip muscles of the affected hand will be trained with a JAMAR® dynamometer. Training will start at 50% of 1RM and progress by 10% each week to reach 80% of 1RM by week 4. The same gradation of intensity will be applied to the grip muscles. The training will begin and end by a 5-minute warm-up and relaxation period comprising of active movements of the trained muscles.

Intervention Type: PROCEDURE

Cranial nerve non-invasive neuromodulation (CN-NINM)

During each strength training session, the CN-NINM will be applied, with the help of a portable stimulator comprising a network of 18 electrodes, directly on the tongue of the participants for 20 minutes. The participants will hold the CN-NINM in place by pressing their tongue upwards. The CN-NINM will generate high-frequency pulses (50 μsec to 150 Hz), and the intensity of the stimulus will be set by each participant to a comfortable level of sensation, similar to the sensation in the mouth of a soft drink.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Université de Sherbrooke

OTHER

Sponsor Role: lead

Responsible Party

Marie-Hélène Milot

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marie-Hélène Milot, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke

Guillaume Léonard, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke

Locations

Centre de recherche sur le vieillissement

Sherbrooke, Quebec, Canada

Countries

Canada

References

Ahiatsi M, Leonard G, Riesco E, Girard MC, Milot MH. A feasibility study on the use of cranial nerve non-invasive neuromodulation to improve affected arm function in people in the chronic stage of a stroke. BMC Neurol. 2025 May 16;25(1):208. doi: 10.1186/s12883-025-04213-5.

Reference Type: DERIVED

PMID: 40380081 (View on PubMed)

Other Identifiers

2022-4609

Identifier Type: -

Identifier Source: org_study_id