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Newborns who are born premature or suffer brain injury at birth are at risk for motor problems that may cause weakness in reaching and grasping on one side of the body. In older children, therapists may use a hand mitt and restraint for the stronger arm, to encourage use of the weaker side, called constraint-induced movement therapy (CIMT). Even with the high intensity therapy of CIMT, it typically takes between 40-120 hours total treatment time for most children to improve their motor skills. A non-invasive form of nerve stimulation, transcutaneous auricular vagus nerve stimulation (taVNS), stimulates a nerve by the ear that enhances learning motor skills. taVNS stimulation will be triggered by EMG sensors which detect muscle activity. The purpose of this study is to evaluate the safety and effectiveness of taVNS to improve motor skills when paired with CIMT in infants with one-sided weakness at 6-18 months of age.
Preterm birth and complications in term births can result in increased risk for intraventricular hemorrhage, global hypoxia-ischemia (HIE), arterial stoke, and neuroinflammation with white matter injury in newborns. Centeral Nervous System (CNS) injuries then may manifest as early developmental delays and motor weakness in the first 12 months, that presage hemiplegic cerebral palsy (CP).
Early targeted therapy interventions for high-risk infants aim to improve neurological outcomes by taking advantage of critical windows for neuroplasticity. Intensive interventions, such as constraint-induced movement therapy (CIMT), are designed to ameliorate early motor predecessors of CP in at-risk infants. This intervention must be provided at a minimally effective dosage of 40 hours, and 60-120 hours for optimal outcomes, and are typically provided in a condensed time period, over 4 to 6 weeks with intensive task-practice for 3-6 hours a day. Delivering CIMT within the context a typical family day is a challenge. Interventional strategies that reduce the time requirement while offering the same or better outcomes would benefit families and facilitate treatment delivery.
Few studies have used neuromodulation combined with intensive motor therapies, such as CIMT, to enhance neuroplasticity and improve functional outcomes in children. Transcranial direct current stimulation has been used safely in older children with CP during bimanual learning therapy. Our group is the first to use non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) paired with a motor task of bottle-feeding in infants with feeding failure. taVNS paired with motor feeding activity was safe and over 50% infants determined to need a gastrostomy tube (G-tube) attained full oral feeds (mean time to full oral feeds 15 days with once daily, and 7.8 days with twice daily treatment). This study will use EMG sensing of muscle activity to trigger the taVNS system. Use of EMG sensors is hypothesized to improve pairing of stimulation with motor activity while also decreasing the treatment burden for the therapist.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EMG triggering feasibility | Experimental | We will trial use of a new taVNS unit that uses automated EMG sensors to trigger stimulation and an optional Bluetooth manual trigger. This experimental device will be used to during CIMT rehabilitation treatment to pair stimulation with active movement. |
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| taVNS and EMG feasibility at home | Experimental | For the 2nd phase of the study we will trial using the EMG triggered system to deliver taVNS and CIMT in the home setting. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Custom EMG triggered Soterix taVNS stimulation with CIMT therapy in lab | Combination Product | Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session. Phase 1 will occur in the lab, and ongoing notifications will be made to the EMG system to test feasibility of automatic stimulation |
| Measure | Description | Time Frame |
|---|---|---|
| Device Feasibility | Feasibility is measured as percent of total treatment time Electromyography (EMG) can successfully trigger stimulation during a Constraint induced movement therapy (CIMT) rehabilitation session. | end of 4 week treatment intervention (40 hours of CIMT) |
| Measure | Description | Time Frame |
|---|---|---|
| Fidelity of Implementation Measure (FIRM) | Fidelity Rating of Quality of Constraint Induced Movement Therapy Delivery while using the experimental EMG triggered Soterix taVNS stimulator. Fidelity of Implementation Measure (FIRM) which describes how consistently therapists exhibit behaviors consistent with CIMT principles and operant conditioning techniques and are rated on a scale of 1-4. A 4 being consistently demonstrating with less than 1 exception, and 1 being rarely or not at all. A score of 3 indicates acceptable to high fidelity. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
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All participants received 40 hours of CIMT paired with taVNS. The first 2 participants received treatment in the lab so the engineer could address sensor calibration and settings to automate EMG triggering. The remaining participants received the same 40 hours of CIMT paired with taVNS in the home setting with the goal to test feasibility of translation of the new EMG triggered taVNS into standard home therapy settings. Participants were told if they would be in home or lab before consent.
Recruitment occurred through flyers in the local hospital and clinics. Flyers were provided to high-risk infant follow-up clinics to be distributed to eligible parents.
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| ID | Title | Description |
|---|---|---|
| FG000 | Custom EMG Triggered Soterix taVNS Stimulation With CIMT Therapy in Lab | Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session. Phase 1 will occur in the lab, and ongoing notifications will be made to the EMG system to test the feasibility of automatic stimulation |
| FG001 | Custom EMG Triggered Soterix taVNS Stimulation With CIMT Therapy in Home | Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session. Phase 2 will occur in the home and will assess the quality of the CIMT therapy provided with the automated EMG system. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Custom EMG Triggered Soterix taVNS Stimulation With CIMT Therapy in Lab | Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session. Phase 1 will occur in the lab, and ongoing notifications will be made to the EMG system to test feasibility of automatic stimulation |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Device Feasibility | Feasibility is measured as percent of total treatment time Electromyography (EMG) can successfully trigger stimulation during a Constraint induced movement therapy (CIMT) rehabilitation session. | Posted | Mean | Full Range | percent time EMG taVNS stimulation | end of 4 week treatment intervention (40 hours of CIMT) |
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Study staff were in daily contact with participants throughout treatment. After the 4 week interventions, we followed up at 3 months up to 4 months post for final assessments.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Soterix taVNS Stimulation Using EMG Sensors | We will trial use of a new taVNS unit that uses automated EMG sensors to trigger stimulation and an optional Bluetooth manual trigger. This experimental device will be used to during CIMT rehabilitation treatment to pair stimulation with active movement. Custom EMG triggered Soterix taVNS stimulation with CIMT therapy: Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session. |
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The purpose of this trial was to test the feasibility of using EMG to trigger taVNS stimulation. The EMG sensors did not stay in place well for some infants. Additionally, there was a large amount of time and effort required for individual calibration. We met the goal threshold of phase 1 for our EMG sensor to trigger taVNS stimulation. However, the automatic triggering did not continue to work well for subsequent participants.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kelly McGloon | Medical University of South Carolina | 8437926443 | mcgloon@musc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 12, 2022 | Mar 18, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 25, 2023 | Mar 5, 2024 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D002547 | Cerebral Palsy |
| ID | Term |
|---|---|
| D001925 | Brain Damage, Chronic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D007753 | Laboratories |
| D006699 | Home Care Services |
| ID | Term |
|---|---|
| D000072182 | Non-Medical Public and Private Facilities |
| D006268 | Health Facilities |
| D005159 | Health Care Facilities Workforce and Services |
| D003153 | Community Health Services |
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For this study we are making modifications to the taVNS stimulation (Soterix unit) system. These modifications include using Electromyography (EMG) muscle sensors to trigger stimulation instead of a manual button. We are also transitioning the manual stimulation option to Bluetooth to improve ease of use in the clinic with infants. The taVNS stimulation will be paired with constraint induced movement therapy (CIMT) an established rehabilitation intervention. The Soterix taVNS unit is FDA registered and is a custom version of an FDA cleared device. The first 2 participants will complete phase 1 of the study. In this phase we will make adjustments to the EMG system and physical set up with the goal of having the EMG sensors trigger taVNS stimulation with 75% of total time for active arma and trunk movements during CIMT. In phase 2 we will use the EMG triggered taVNS setup to deliver CIMT in home.
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| Custom EMG triggered Soterix taVNS stimulation with CIMT therapy in home | Combination Product | Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session. Phase 2 will occur in the home and will assess the quality of the CIMT therapy provided with the automated EMG system. |
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| end of 4 week treatment intervention (40 hours of CIMT) |
| Quality of Upper Extremity Skills Test (QUEST) | Quality of Upper Extremity Skills Test The QUEST is a criterion-referenced measure designed to evaluate the quality of upper extremity function in young children with spasticity. We calculated scores from 2 domains:1) Dissociated movement and2) Grasp Item scores are summed; formulas are used to calculate percentages for each domain. Domain percentages are summed and divided by number of domains (2 for our study) to obtain total score. Minimum score = 0; Maximum score = 100 The total QUEST score was calculated by summing scores for each sub-domain tested divided by the total number of sub-domains tested. The total scores on the QUEST range from 0 to 100. Higher scores represent better quality of movement. | Change in functional motor outcome completed pre and post 40 hours of treatment |
| BG001 | Custom EMG Triggered Soterix taVNS Stimulation With CIMT Therapy in Home | Participants will receive taVNS stimulation paired with 40 hours of constraint-induced movement therapy. The new device will automatically trigger stimulation using EMG muscle sensors worn during the therapy session. Phase 2 will occur in the home and will assess the quality of the CIMT therapy provided with the automated EMG system. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Full Range | months |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Gross Motor Functional Measure (GMFM) function at baseline | Gross Motor Functional Measure The GMFM consists of 5 domains: a)Lying & Rolling, b)Sitting, c)Crawling & Kneeling, d) Standing, and e) Walking, Running & Jumping. Each item in the test uses a 4-point scale: 0=does not initiate; 1=initiates but completes less than 10%; 2=partially completes (10% to less than 100%); and 3=fully completes the task. Item scores are summed to calculate raw and percent scores for each of the five domains. Domain percent scores are averaged to obtain an overall total score. Higher scores represent higher levels of function. The total score range is 0 to 100%. | Mean | Full Range | Gross Motor Functional Measure 66 score |
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| Units | Counts |
|---|
| Participants |
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| Secondary | Fidelity of Implementation Measure (FIRM) | Fidelity Rating of Quality of Constraint Induced Movement Therapy Delivery while using the experimental EMG triggered Soterix taVNS stimulator. Fidelity of Implementation Measure (FIRM) which describes how consistently therapists exhibit behaviors consistent with CIMT principles and operant conditioning techniques and are rated on a scale of 1-4. A 4 being consistently demonstrating with less than 1 exception, and 1 being rarely or not at all. A score of 3 indicates acceptable to high fidelity. | Even though we met the threshold to move to trialing the EMG triggered taVNS in home we faced technical issues with the EMG triggering interface. We completed the full 40 hours of CIMT therapy but could not use EMG triggered taVNS stimulation. Therefore, we were not able to rate the fidelity of the CIMT treatment with TMG triggered taVNS because the EMG system did not function properly. Our 2nd participant withdrew and therefore, we were again not able to rate the fidelity of implementation. | Posted | end of 4 week treatment intervention (40 hours of CIMT) |
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| Secondary | Quality of Upper Extremity Skills Test (QUEST) | Quality of Upper Extremity Skills Test The QUEST is a criterion-referenced measure designed to evaluate the quality of upper extremity function in young children with spasticity. We calculated scores from 2 domains:1) Dissociated movement and2) Grasp Item scores are summed; formulas are used to calculate percentages for each domain. Domain percentages are summed and divided by number of domains (2 for our study) to obtain total score. Minimum score = 0; Maximum score = 100 The total QUEST score was calculated by summing scores for each sub-domain tested divided by the total number of sub-domains tested. The total scores on the QUEST range from 0 to 100. Higher scores represent better quality of movement. | We completed analysis on the 3 participants who received 40 hours of CIMT therapy paired with taVNS. The 2nd participant in the home group withdrew and did not complete the 40 hours of therapy so change in function was not assessed. | Posted | Mean | Full Range | score on a scale | Change in functional motor outcome completed pre and post 40 hours of treatment |
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| D006296 | Health Services |
| D009739 | Nursing Services |