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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DC012584-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Deafness and Other Communication Disorders (NIDCD) | NIH |
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Swallowing difficulties are common after a stroke and can lead to serious complications like pneumonia and malnutrition. Unfortunately, there are no effective treatment for improving swallowing in stroke patients.
Previous investigations have shown that recovery of swallowing functions occurs from reorganization ("rewiring") of the non-involved cerebral hemisphere. In this study, the investigators propose to investigate a new intervention, which combines, swallowing exercises with brain stimulation targeted to the non-involved cerebral hemisphere, using low intensity current in acute stroke patients. The investigators plan to assess the safety of this technique in this patient population and also assess its effect on improving swallowing functions and swallowing physiology. During this time trial participants will undergo standardized swallowing and neurological assessments as well as brain MRI scans.
Swallowing impairments are a common and a serious complication of stroke but lack effective therapies. The study investigators herein propose to conduct a prospective clinical study using a non-invasive brain stimulation technique, anodal transcranial direct current stimulation (tDCS), in combination with swallowing exercises for improving dysphagia due to an acute-subacute hemispheric infarction, and obtain data on safety and effect of 2 different doses of tDCS, on swallowing physiology and behavior. Dysphagia from hemispheric strokes occurs due to disruption of the cortical projections to the brainstem swallowing centers while recovery of swallowing functions have been shown to be mediated via the reorganization of the swallowing cortex in the unaffected hemisphere. A recent pilot study conducted by the investigators demonstrated the safety and feasibility of applying 5 consecutive daily sessions of anodal tDCS for 30 minutes to the swallowing cortex on the unaffected hemisphere in the acute-subacute stroke phases and showed a promise in improving dysphagia, when combined with swallowing exercises. The proposed research will be used to further confirm safety of this technique in early stroke phases and explore alternative, more effective doses for promoting swallowing recovery prior to its examination in any confirmatory trials. The investigators will use the study cohort to examine important subject specific parameters which influence response to the proposed intervention in dysphagic stroke patients. The overall aim of this study is to gather additional safety data on cumulative sessions of tDCS in acute-subacute phases of stroke, obtain information about effects of this intervention on important physiological and clinically relevant swallowing parameters, examine possible dose effects, and identify candidates who are more likely to benefit from this intervention. The experience gained from this project will guide planning of future confirmatory trials that use relevant clinical outcomes to assess potential benefits of this intervention and utilize important subject specific parameters to refine study inclusion criteria and aid in severity adjusted analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High dose anodal tDCS | Experimental | High dose tDCS (2 milliamps twice daily) for 5 days will be administered concomitantly with swallowing exercises |
|
| Low dose anodal tDCS | Active Comparator | This arm will use a low dose of current administered via tDCS (2 milliamps once daily) for 5 days will be administered concomitantly with swallowing exercises |
|
| Sham Stimulation | Sham Comparator | Twice daily swallowing exercises only |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tDCS | Device | Anodal tDCS will be administered with swallowing exercises |
|
| Measure | Description | Time Frame |
|---|---|---|
| To Assess Changes in Penetration and Aspiration | This will be assessed using the Penetration and Aspiration Scale (PAS) scores, a validated 8 point ordinal scale that quantifies penetration and aspiration events observed during Videofluoroscopic Swallowing Evaluation. PAS ranges from 1 (best score) representing no aspiration or penetration to 8 (worst score) representing severe aspiration. An average PAS score will be computed based on 9 swallows for this outcome. | Scores will be measured before tDCS and after 5 days after completion of stimulation |
| To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Seizures in Each of the 3 Groups | We will tabulate the number of participants who develop seizures in the High-dose anodal tDCS, Low-dose anodal tDCS and Sham stimulation groups. | During the 5 days of stimulation sessions |
| To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Deaths in Each of the 3 Groups Attributable to the Direct Effects of Stroke | We will tabulate the number of deaths in High-dose tDCS, Low-dose tDCS and Sham stimulation groups, that are attributable to the direct effects of the qualifying stroke. | During the 5 days of stimulation sessions |
| To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Neurological Deterioration in Each of the 3 Groups | We will tabulate the number of participants who develop neurological deterioration in the High-dose tDCS, Low-dose tDCS and Sham groups. Neurological deterioration will be defined as an increase in the total National Institute of Health Stroke Scale (NIHSS) Score by 4 or more points between each successive day. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. NIHSS ranges from 0 (normal) to 42 (worst possible score). Higher scores mean worse neurological functions. |
| Measure | Description | Time Frame |
|---|---|---|
| To Assess and Compare Changes in Dietary Intake in Each of the Three Groups | The durability of any observed effects of the intervention on dietary status will be estimated by changes in Functional Oral Intake Scale (FOIS) score. FOIS is an ordinal scale ranging from 1 (worst) to 7 (normal oral diet) and provides a reliable measure of dietary intake. The change in FOIS scores across each group will be compared. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sandeep Kumar, MD | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25534369 | Background | Marchina S, Schlaug G, Kumar S. Study design for the fostering eating after stroke with transcranial direct current stimulation trial: a randomized controlled intervention for improving Dysphagia after acute ischemic stroke. J Stroke Cerebrovasc Dis. 2015 Mar;24(3):511-20. doi: 10.1016/j.jstrokecerebrovasdis.2014.09.027. Epub 2014 Dec 19. |
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A total of 328 subjects were screened for the trial, of which 214 did not fulfill all trial criteria and 72 refused consent. A total of 42 subjects were eventually enrolled: 14 subjects in High-Dose tDCS, 13 in Low-Dose tDCS and 15 in Sham arms.
All subjects were recruited from the inpatient neurology/stroke service at Beth Israel Deaconess Medical Center, Boston, MA. The first subject was recruited on 2/10/2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | High Dose Anodal tDCS | High dose tDCS (2 milliamps twice daily) for 5 days will be administered concomitantly with swallowing exercises tDCS: Anodal tDCS will be administered with swallowing exercises |
| FG001 | Low Dose Anodal tDCS | This arm will use a low dose of current administered via tDCS (2 milliamps once daily) for 5 days will be administered concomitantly with swallowing exercises tDCS: Anodal tDCS will be administered with swallowing exercises |
| FG002 | Sham Stimulation | Twice daily swallowing exercises only tDCS: Anodal tDCS will be administered with swallowing exercises |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary Analysis-day 5 of Intervention |
| |||||||||||||
| Secondary Analysis-day 30 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | High Dose Anodal tDCS | High dose tDCS (2 milliamps twice daily) for 5 days will be administered concomitantly with swallowing exercises tDCS: Anodal tDCS will be administered with swallowing exercises |
| BG001 | Low Dose Anodal tDCS |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | To Assess Changes in Penetration and Aspiration | This will be assessed using the Penetration and Aspiration Scale (PAS) scores, a validated 8 point ordinal scale that quantifies penetration and aspiration events observed during Videofluoroscopic Swallowing Evaluation. PAS ranges from 1 (best score) representing no aspiration or penetration to 8 (worst score) representing severe aspiration. An average PAS score will be computed based on 9 swallows for this outcome. | Analysis of participant was based on an intention to treat principle. | Posted | Mean | Standard Deviation | score on a scale | Scores will be measured before tDCS and after 5 days after completion of stimulation |
|
Adverse event data were collected over the entire duration of patient follow-up (30 days since trial enrollment).
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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 | High Dose Anodal tDCS | High dose tDCS (2 milliamps twice daily) for 5 days will be administered concomitantly with swallowing exercises tDCS: Anodal tDCS will be administered with swallowing exercises |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sandeep Kumar, MD | Beth Israel Deaconess Medical Center | 617-632-8917 | skumar@bidmc.harvard.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 | Aug 14, 2014 | May 27, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003680 | Deglutition Disorders |
| D020521 | Stroke |
| ID | Term |
|---|---|
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D010608 | Pharyngeal Diseases |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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The trial will randomize subjects to anodal transcranial direct current stimulation (tDCS) versus sham stimulation, both of them carried out in combination with standardized swallowing exercises
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Investigators and subjects will be masked to the trail arm assignments at randomization. The investigator reviewing outcome data will also be masked to the trial assignments.
| During the 5 days of stimulation sessions |
| To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Motor Deterioration in Each of the 3 Groups | We will tabulate the number of participants with deterioration in their motor functions in the High-dose tDCS, Low-dose tDCS and Sham groups. Motor deterioration will be defined as an increase in the motor sub-item of the National Institute of Health Stroke Scale (NIHSS) score by 2 or more points between each successive day of stimulation. The motor sub-item of the NIHSS ranges from 0 (normal) to 16 (worst possible score), with higher scores indicating a worse motor exam. | During the 5 days of stimulation sessions |
| To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Swallowing Deterioration in Each of the 3 Groups | We will tabulate the number of participants with swallowing deterioration in the High-dose tDCS, Low-dose tDCS and sham groups Swallowing deterioration will be defined as an increase in the score by 2 or more points in the Functional Oral Intake Scale (FOIS). FOIS provides a validated measure of diet level. FOIS is an ordinal scale ranging from 7 (normal diet) to 0 (no oral intake), with lower scores indicating a worse diet. | Any change between day 1 and day 3 of stimulation session |
| At study onset and after 1 month |
| To Assess Changes in Physiological Measures of Pharyngeal Strength | Examining effects of differing doses of anodal tDCS versus sham stimulation on Pharyngeal Constriction Ratio (PCR), derived from videofluoroscopic swallowing studies.PCR is a measure of the pharyngeal area visible in the lateral radiograph view at the point when a bolus is held in the oral cavity divided by the pharyngeal area at the point of maximum pharyngeal constriction during the swallow. A higher PCR indicates a weak swallow leading to increased food residue in the pharynx. | Variables will be measured at baseline (before starting tDCS) and after 5 days after completion of stimulation |
| To Assess Changes in Physiological Measures of Briskness of Swallow Onset | Examining effects of differing doses of anodal tDCS versus sham stimulation on Pharyngeal Delay Time (PDT) , derived from videofluoroscopic swallowing studies. PDT is defined as the time in centiseconds that the bolus is present in the hypopharynx before the swallow is triggered. PDT is a temporal measure of the briskness of the swallow onset. | Variables will be measured at baseline (before starting tDCS) and after 5 days after completion of stimulation |
| To Assess Changes in Physiological Measures of Laryngeal Excursion | Examining effects of differing doses of anodal tDCS versus sham stimulation on measure of actual excursion of the larynx in centimeters from their resting point to maximal excursion, derived from videofluoroscopic swallowing studies. | Variables will be measured at baseline (before starting tDCS) and after 5 days after completion of stimulation |
| Change in PAS Scores as an Indicator of Dysphagia Recovery After Covariate Adjustment | We will examine the effects of the intervention in a linear model by using it as a predictor for dysphagia recovery along with other variables of interest [age, baseline National Institute of Health Stroke Scale and Penetration and Aspiration Scale (PAS) scores], with a change in PAS scores from baseline to day 5 of the intervention, as being the outcome of interest. | At day 5 of study participation |
| NOT COMPLETED |
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This arm will use a low dose of current administered via tDCS (2 milliamps once daily) for 5 days will be administered concomitantly with swallowing exercises
tDCS: Anodal tDCS will be administered with swallowing exercises
| BG002 | Sham Stimulation | Twice daily swallowing exercises only tDCS: Anodal tDCS will be administered with swallowing exercises |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Penetration and Aspiration Scale Score | This is a validated 8 point ordinal scale (range 1-8; score 1 is normal and 8 is the worst possible) that quantifies penetration and aspiration events observed during a videofluroscopic swallowing study (VFSS). All PAS scores were assigned by an independent evaluator blinded to intervention allocation and were based on a standardized VFSS. | Mean | Standard Deviation | units on a scale |
|
| OG001 | Low Dose Anodal tDCS | This arm will use a low dose of current administered via tDCS (2 milliamps once daily) for 5 days will be administered concomitantly with swallowing exercises tDCS: Anodal tDCS will be administered with swallowing exercises |
| OG002 | Sham Stimulation | Twice daily swallowing exercises only tDCS: Anodal tDCS will be administered with swallowing exercises |
|
|
| Primary | To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Seizures in Each of the 3 Groups | We will tabulate the number of participants who develop seizures in the High-dose anodal tDCS, Low-dose anodal tDCS and Sham stimulation groups. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Count of Participants | Participants | During the 5 days of stimulation sessions |
|
|
|
| Primary | To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Deaths in Each of the 3 Groups Attributable to the Direct Effects of Stroke | We will tabulate the number of deaths in High-dose tDCS, Low-dose tDCS and Sham stimulation groups, that are attributable to the direct effects of the qualifying stroke. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Count of Participants | Participants | During the 5 days of stimulation sessions |
|
|
|
| Primary | To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Neurological Deterioration in Each of the 3 Groups | We will tabulate the number of participants who develop neurological deterioration in the High-dose tDCS, Low-dose tDCS and Sham groups. Neurological deterioration will be defined as an increase in the total National Institute of Health Stroke Scale (NIHSS) Score by 4 or more points between each successive day. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. NIHSS ranges from 0 (normal) to 42 (worst possible score). Higher scores mean worse neurological functions. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Count of Participants | Participants | During the 5 days of stimulation sessions |
|
|
|
| Primary | To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Motor Deterioration in Each of the 3 Groups | We will tabulate the number of participants with deterioration in their motor functions in the High-dose tDCS, Low-dose tDCS and Sham groups. Motor deterioration will be defined as an increase in the motor sub-item of the National Institute of Health Stroke Scale (NIHSS) score by 2 or more points between each successive day of stimulation. The motor sub-item of the NIHSS ranges from 0 (normal) to 16 (worst possible score), with higher scores indicating a worse motor exam. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Count of Participants | Participants | During the 5 days of stimulation sessions |
|
|
|
| Primary | To Assess Safety of tDCS in Acute-subacute Stroke Phase: Number of Participants With Swallowing Deterioration in Each of the 3 Groups | We will tabulate the number of participants with swallowing deterioration in the High-dose tDCS, Low-dose tDCS and sham groups Swallowing deterioration will be defined as an increase in the score by 2 or more points in the Functional Oral Intake Scale (FOIS). FOIS provides a validated measure of diet level. FOIS is an ordinal scale ranging from 7 (normal diet) to 0 (no oral intake), with lower scores indicating a worse diet. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Count of Participants | Participants | Any change between day 1 and day 3 of stimulation session |
|
|
|
| Secondary | To Assess and Compare Changes in Dietary Intake in Each of the Three Groups | The durability of any observed effects of the intervention on dietary status will be estimated by changes in Functional Oral Intake Scale (FOIS) score. FOIS is an ordinal scale ranging from 1 (worst) to 7 (normal oral diet) and provides a reliable measure of dietary intake. The change in FOIS scores across each group will be compared. | Analyzed on an intention to treat analysis | Posted | Mean | Standard Deviation | score on a scale | At study onset and after 1 month |
|
|
|
| Secondary | To Assess Changes in Physiological Measures of Pharyngeal Strength | Examining effects of differing doses of anodal tDCS versus sham stimulation on Pharyngeal Constriction Ratio (PCR), derived from videofluoroscopic swallowing studies.PCR is a measure of the pharyngeal area visible in the lateral radiograph view at the point when a bolus is held in the oral cavity divided by the pharyngeal area at the point of maximum pharyngeal constriction during the swallow. A higher PCR indicates a weak swallow leading to increased food residue in the pharynx. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Mean | Standard Deviation | Ratio | Variables will be measured at baseline (before starting tDCS) and after 5 days after completion of stimulation |
|
|
|
| Secondary | To Assess Changes in Physiological Measures of Briskness of Swallow Onset | Examining effects of differing doses of anodal tDCS versus sham stimulation on Pharyngeal Delay Time (PDT) , derived from videofluoroscopic swallowing studies. PDT is defined as the time in centiseconds that the bolus is present in the hypopharynx before the swallow is triggered. PDT is a temporal measure of the briskness of the swallow onset. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Mean | Standard Deviation | centiseconds | Variables will be measured at baseline (before starting tDCS) and after 5 days after completion of stimulation |
|
|
|
| Secondary | To Assess Changes in Physiological Measures of Laryngeal Excursion | Examining effects of differing doses of anodal tDCS versus sham stimulation on measure of actual excursion of the larynx in centimeters from their resting point to maximal excursion, derived from videofluoroscopic swallowing studies. | Analyzed on an intention to treat as well as per protocol analysis | Posted | Mean | Standard Deviation | centimeters | Variables will be measured at baseline (before starting tDCS) and after 5 days after completion of stimulation |
|
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| Secondary | Change in PAS Scores as an Indicator of Dysphagia Recovery After Covariate Adjustment | We will examine the effects of the intervention in a linear model by using it as a predictor for dysphagia recovery along with other variables of interest [age, baseline National Institute of Health Stroke Scale and Penetration and Aspiration Scale (PAS) scores], with a change in PAS scores from baseline to day 5 of the intervention, as being the outcome of interest. | Posted | Median | Standard Error | score on a scale | At day 5 of study participation |
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| 1 |
| 14 |
| 1 |
| 14 |
| 3 |
| 14 |
| EG001 | Low Dose Anodal tDCS | This arm will use a low dose of current administered via tDCS (2 milliamps once daily) for 5 days will be administered concomitantly with swallowing exercises tDCS: Anodal tDCS will be administered with swallowing exercises | 1 | 13 | 1 | 13 | 2 | 13 |
| EG002 | Sham Stimulation | Twice daily swallowing exercises only tDCS: Anodal tDCS will be administered with swallowing exercises | 1 | 15 | 2 | 15 | 3 | 15 |
| Pneumonia | Infections and infestations | Systematic Assessment |
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| hyperglycemia | Endocrine disorders | Systematic Assessment |
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| diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Tachycardia | Cardiac disorders | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | Systematic Assessment |
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| Metabolic disorder | Endocrine disorders | Systematic Assessment |
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| D010038 | Otorhinolaryngologic Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |
Regression models using interaction terms will used to assess for heterogeneity of intervention effects across the novel radiological variable corticobulbar tract (CBT)-lesion load, a combined measure of lesion size and location. For purposes of the analysis, the CBT-lesion load was dichotomized into 2 groups based on the median CBT-lesion load volume. |