Alzheimer Disease, Dementia, Multiple Sclerosis, Oropharyngeal Dysphagia, Parkinson Disease, Stroke
Conditions
Brief summary
The study procedure of simultaneous VFSS and DDS measurement will be completed in one day and the subject will be followed within 2 business days after the study procedure to monitor for adverse events.
Detailed description
DDS signals and VFSS will be recorded simultaneously (for the same bolus) using barium contrast agent stimuli prepared in three consistencies: thin, mildly-thick and moderately-thick. Subjects will undergo VFSS with simultaneous DDS using up to 5 boluses of thin barium stimulus (THIN-Ba), and up to 4 boluses of barium thickened to mildly (MILD-Ba) thick and up to 4 boluses of moderately (MODERATE-Ba) thick barium consistencies using Resource Thicken Up Clear Nestlé Health Science (TUC). 4, 3 and 3 boluses for THIN-Ba, MILD-Ba and MOD-Ba will be analyzed using the classifier algorithms for sensitivity/specificity results. According to the exploratory trial, VFSS data for safety or efficiency can be missing for up to 14% boluses due to quality of VFSS recording. To compensate for potential losses of boluses due to missing gold standard (VFSS) data, 5, 4 and 4 boluses will be collected for the three consistencies respectively . The DDS signals will be sent to a dedicated application software installed at the CRO, which interprets the acceleration data and displays the examination result. The VFSS recording will be sent to CRO and provided for blinded assessment by the independent central VFSS laboratory.The study procedure of simultaneous VFSS and DDS measurement will be completed in one day and the subject will be followed within 2 business days after the study procedure to monitor for adverse events.
Interventions
DEVICEDysphagia Detection System
The Nestle Health Sciences (NHSc) Dysphagia Detection System (DDS) is a portable, non-invasive device designed for use at the bedside. The investigational DDS has 3 basic components: Sensor Unit (suspended on a necklace), Sensor Fixation and a personal computer (PC) for collecting data. The Sensor Unit consists of a dual-axis accelerometer in a plastic housing that is attached to the front of a patient's neck just below the thyroid cartilage by the single-use, disposable fixation unit. The Sensor Unit is connected via a cable to an A/D converter which then connects via cable to the PC. The PC collects the examination data, which is then sent to dedicated application software (installed at the CRO), which interprets the acceleration data and displays the examination result.
Sponsors
Cytel Inc.
Regulatory and Clinical Research Institute Inc
Nestec Ltd.
Société des Produits Nestlé (SPN)
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
SCREENING
Masking
NONE
Masking description
An operationally seamless single-arm, prospective, multicenter, single-blinded for central outcomes assessors trial to test DDS in assessing swallowing safety and efficiency in patients at risk of oropharyngeal dysphagia.
Intervention model description
The clinical trial will initially start as a 3-look group sequential design (GSD). Alpha-spending will be calculated using Lan-DeMets spending function (with O'Brien-Fleming parameter). At the first interim analysis (IA-1) the threshold on the ROC curve may be re-computed using the ROC curve generated using the IA-1 data, in which case, the validation trial would start afresh following IA-1 using a 2-look GSD. Data included in the IA-1 would no longer be used for the validation phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult subjects (over 18 years of age) * Hospitalized subjects or outpatients identified as at risk of oropharyngeal dysphagia (using local practice) * Patients belong to one of the following groups: * Stroke patients * Traumatic brain injury * Parkinson Disease (PD) stage III or higher by Hoehn and Yahr scale * Multiple Sclerosis (MS) above age 60 * Alzheimer Disease (AD) or other Dementia * Other medically complex hospitalized subjects not covered by the
Exclusion criteria
and identified as at risk of dysphagia * Subject is able to comply with VFSS protocol to diagnose dysphagia * Subject is able to give voluntary, written informed consent to participate in the clinical investigation and from whom consent has been obtained / or a consultee has consented on he subjects behalf in line with nationally agreed guidelines concerning adults unable to consent for themselves.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Receiver Operating Characteristic (ROC) Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for THIN-Ba | The study procedure of simultaneous VFSS and DDS measurement using thin barium (THIN-Ba) was completed in one day for each subject. | The primary efficacy of the DDS was measured as the sensitivity & specificity obtained from comparing the DDS predicted swallow safety outcome (binary) with the clinical reference standard VFSS swallow safety outcome (binary) for thin barium (THIN-Ba) stimuli, using 5 boluses per subject protocol. ROC (AUC) was used for comparing the 2 algorithms. The ROC curve incorporates both sensitivity (true positive rate) and specificity (true negative rate) providing a single assessment incorporating both measures. The higher the total area under the curve, the greater the predictive power of the outcome. Primary analysis for futility was based on 242 subjects (Interim Analysis). The study was terminated based on futility as the AUC for primary endpoint (0.64) was less than the guiding futility bound of 0.75. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC Under ROC Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for MILD-Ba | The study procedure of simultaneous VFSS and DDS measurement using mild barium (MILD-Ba) was completed in one day for each subject. | The sensitivity & specificity obtained from comparing the DDS predicted swallow safety outcome (binary) with the clinical reference standard VFSS swallow safety outcome (binary) for MILD barium (MILD-Ba) stimuli, using 4 boluses per subject protocol. ROC (AUC) was used for comparing the 2 algorithms. The higher the total AUC, the greater the predictive power of the outcome. |
| AUC Under ROC Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for MOD-Ba | The study procedure of simultaneous VFSS and DDS measurement using MOD-Ba was completed in one day for each subject. | The sensitivity & specificity obtained from comparing the DDS predicted swallow safety outcome (binary) with the clinical reference standard VFSS swallow safety outcome (binary) for MODERATE barium (MOD-Ba) stimuli, using 3 boluses per subject protocol. ROC (AUC) was used for comparing the 2 algorithms. The higher the total AUC, the greater the predictive power of the outcome. |
| The Sensitivity & Specificity for Swallow Efficiency Using THIN-Ba | The study procedure of simultaneous VFSS and DDS measurement using THIN-Ba was completed in one day for each subject. | The sensitivity & specificity obtained from comparing the DDS predicted swallow efficiency outcome (binary) with the clinical reference standard VFSS swallow efficiency outcome (binary) for Thin barium (THIN-Ba) stimuli. |
| The Sensitivity & Specificity for Swallow Efficiency Using MILD-Ba | The study procedure of simultaneous VFSS and DDS measurement using MILD-Ba was completed in one day for each subject. | The sensitivity & specificity obtained from comparing the DDS predicted swallow efficiency outcome (binary) with the clinical reference standard VFSS swallow efficiency outcome (binary) for MILD-Ba. |
| The Sensitivity & Specificity for Swallow Efficiency Using MOD-Ba | The study procedure of simultaneous VFSS and DDS measurement using MOD-Ba was completed in one day for each subject. | The sensitivity & specificity obtained from comparing the DDS predicted swallow efficiency outcome (binary) with the clinical reference standard VFSS swallow efficiency outcome (binary) for MOD-Ba stimuli. |
Countries
Finland, United States
Participant flow
Recruitment details
The trial was stopped on 23 July 2018 when the announcement of futility stopping was made.
Participants by arm
| Arm | Count |
|---|---|
| Single-arm Dysphagia Detection System An operationally seamless single-arm, prospective, multicenter, single-blinded for central outcomes assessors trial to test DDS in assessing swallowing safety and efficiency in patients at risk of oropharyngeal dysphagia.
Dysphagia Detection System: The Nestle Health Sciences (NHSc) Dysphagia Detection System (DDS) is a portable, non-invasive device designed for use at the bedside. The investigational DDS has 3 basic components: Sensor Unit (suspended on a necklace), Sensor Fixation and a personal computer (PC) for collecting data. The Sensor Unit consists of a dual-axis accelerometer in a plastic housing that is attached to the front of a patient's neck just below the thyroid cartilage by the single-use, disposable fixation unit. The Sensor Unit is connected via a cable to an A/D converter which then connects via cable to the PC. The PC collects the examination data, which is then sent to dedicated application software (installed at the CRO), which interprets the acceleration data and displays the examination result. | 452 |
| Total | 452 |
Baseline characteristics
| Characteristic | Single-arm Dysphagia Detection System |
|---|---|
| Age, Continuous | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 20 Participants |
| Race (NIH/OMB) Black or African American | 78 Participants |
| Race (NIH/OMB) More than one race | 17 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 331 Participants |
| Sex: Female, Male Female | 166 Participants |
| Sex: Female, Male Male | 286 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 438 |
| other Total, other adverse events | 0 / 438 |
| serious Total, serious adverse events | 5 / 438 |
Outcome results
Primary
Area Under the Receiver Operating Characteristic (ROC) Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for THIN-Ba
The primary efficacy of the DDS was measured as the sensitivity & specificity obtained from comparing the DDS predicted swallow safety outcome (binary) with the clinical reference standard VFSS swallow safety outcome (binary) for thin barium (THIN-Ba) stimuli, using 5 boluses per subject protocol. ROC (AUC) was used for comparing the 2 algorithms. The ROC curve incorporates both sensitivity (true positive rate) and specificity (true negative rate) providing a single assessment incorporating both measures. The higher the total area under the curve, the greater the predictive power of the outcome. Primary analysis for futility was based on 242 subjects (Interim Analysis). The study was terminated based on futility as the AUC for primary endpoint (0.64) was less than the guiding futility bound of 0.75.
Time frame: The study procedure of simultaneous VFSS and DDS measurement using thin barium (THIN-Ba) was completed in one day for each subject.
Population: The interim analysis data consists of all subjects enrolled and completed before the data cut-off date. The analysis data set consisted of N=253 subjects with N=242 subjects meeting all inclusion-exclusion criteria and having at least one successfully completed Thin bolus swallow measurement (both VFS and DDS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single-arm Dysphagia Detection System | Area Under the Receiver Operating Characteristic (ROC) Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for THIN-Ba | 0.64 Probability |
Secondary
AUC Under ROC Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for MILD-Ba
The sensitivity & specificity obtained from comparing the DDS predicted swallow safety outcome (binary) with the clinical reference standard VFSS swallow safety outcome (binary) for MILD barium (MILD-Ba) stimuli, using 4 boluses per subject protocol. ROC (AUC) was used for comparing the 2 algorithms. The higher the total AUC, the greater the predictive power of the outcome.
Time frame: The study procedure of simultaneous VFSS and DDS measurement using mild barium (MILD-Ba) was completed in one day for each subject.
Population: Primary analysis for futility was based on 242 subjects (Interim Analysis).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single-arm Dysphagia Detection System | AUC Under ROC Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for MILD-Ba | 0.65 Probability |
Secondary
AUC Under ROC Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for MOD-Ba
The sensitivity & specificity obtained from comparing the DDS predicted swallow safety outcome (binary) with the clinical reference standard VFSS swallow safety outcome (binary) for MODERATE barium (MOD-Ba) stimuli, using 3 boluses per subject protocol. ROC (AUC) was used for comparing the 2 algorithms. The higher the total AUC, the greater the predictive power of the outcome.
Time frame: The study procedure of simultaneous VFSS and DDS measurement using MOD-Ba was completed in one day for each subject.
Population: Primary analysis for futility was based on 242 subjects (Interim Analysis).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single-arm Dysphagia Detection System | AUC Under ROC Curve to Compare the DDS Predicted Swallow Safety Outcome (Binary) vs. Clinical Reference Standard VFS for MOD-Ba | 0.576 Probability |
Secondary
The Sensitivity & Specificity for Swallow Efficiency Using MILD-Ba
The sensitivity & specificity obtained from comparing the DDS predicted swallow efficiency outcome (binary) with the clinical reference standard VFSS swallow efficiency outcome (binary) for MILD-Ba.
Time frame: The study procedure of simultaneous VFSS and DDS measurement using MILD-Ba was completed in one day for each subject.
Population: The analysis for secondary endpoints were to be carried out in a hierarchical fashion in the specified order, only if primary endpoint was met:~1. swallow safety using MILD-Ba~2. swallow safety using MOD-Ba~3. swallow efficiency using THIN-Ba~4. swallow efficiency using MILD-Ba~5. swallow efficiency using MOD-Ba Outcomes on swallow efficiency were not analyzed.
Secondary
The Sensitivity & Specificity for Swallow Efficiency Using MOD-Ba
The sensitivity & specificity obtained from comparing the DDS predicted swallow efficiency outcome (binary) with the clinical reference standard VFSS swallow efficiency outcome (binary) for MOD-Ba stimuli.
Time frame: The study procedure of simultaneous VFSS and DDS measurement using MOD-Ba was completed in one day for each subject.
Population: The analysis for secondary endpoints were to be carried out in a hierarchical fashion in the specified order, only if primary endpoint was met:~1. swallow safety using MILD-Ba~2. swallow safety using MOD-Ba~3. swallow efficiency using THIN-Ba~4. swallow efficiency using MILD-Ba~5. swallow efficiency using MOD-Ba~Outcomes on swallow efficiency were not analyzed.
Secondary
The Sensitivity & Specificity for Swallow Efficiency Using THIN-Ba
The sensitivity & specificity obtained from comparing the DDS predicted swallow efficiency outcome (binary) with the clinical reference standard VFSS swallow efficiency outcome (binary) for Thin barium (THIN-Ba) stimuli.
Time frame: The study procedure of simultaneous VFSS and DDS measurement using THIN-Ba was completed in one day for each subject.
Population: The analysis for secondary endpoints were to be carried out in a hierarchical fashion in the specified order, only if primary endpoint was met:~1. swallow safety using MILD-Ba~2. swallow safety using MOD-Ba~3. swallow efficiency using THIN-Ba~4. swallow efficiency using MILD-Ba~5. swallow efficiency using MOD-Ba~Outcomes on swallow efficiency were not analyzed.