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This is a 2x2 cross over pilot study using low level transcutaneous vagus nerve stimulation (LLTS) to reverse diastolic dysfunction in patients with diastolic dysfunction. All patients will receive 2 separate, 1-hour sequences, at least 1 day apart, of active and sham LLTS, but the sequence will be randomized. Patients will be randomly assigned (1:1) to active/sham or sham/active LLTS. LLTS will be performed using a transcutaneous electrical nerve stimulation (TENS) device with electrodes attached to the tragus of the ear, which is innervated by auricular branch of the vagus nerve. Echocardiography will be performed after 30 minutes of LLTS or sham stimulation to assess diastolic function. Five-minute ECGs will be obtained for HRV analysis every 15 minutes of stimulation (total of 4 recordings).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham stimulation first | Placebo Comparator | Sham stimulation delivered at the earlobe (devoid of vagal innervation) is given on first session. Transcutaneous vagus nerve stimulation delivered at the tragus (vagal innervation) is given on second session. |
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| Active stimulation first | Active Comparator | Transcutaneous vagus nerve stimulation delivered at the earlobe (vagal innervation) is given on first session. Sham stimulation delivered at the tragus (devoid of vagal innervation) is given on second session. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| transcutaneous vagus nerve stimulation | Device | All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized |
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| Measure | Description | Time Frame |
|---|---|---|
| Echocardiographic Markers of Diastolic Dysfunction | Global longitudinal strain | after 1 hour of stimulation |
| Measure | Description | Time Frame |
|---|---|---|
| Heart Rate Variability Measures | low frequency to high frequency ratio. This is a measure of sympathovagal balance. A lower value reflects a more favorable balance between sympathetic and parasympathetic (vagal) tone. | after 1 hour of stimulation |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30560316 | Derived | Tran N, Asad Z, Elkholey K, Scherlag BJ, Po SS, Stavrakis S. Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans. J Cardiovasc Transl Res. 2019 Jun;12(3):221-230. doi: 10.1007/s12265-018-9853-6. Epub 2018 Dec 17. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sham Stimulation First | Sham stimulation delivered at the earlobe (devoid of vagal innervation) is given on first session. Transcutaneous vagus nerve stimulation delivered at the tragus (vagal innervation) is given on second session. transcutaneous vagus nerve stimulation: All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized |
| FG001 | Active Stimulation First | Transcutaneous vagus nerve stimulation delivered at the earlobe (vagal innervation) is given on first session. Sham stimulation delivered at the tragus (devoid of vagal innervation) is given on second session. transcutaneous vagus nerve stimulation: All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized |
| 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 | Echocardiographic Markers of Diastolic Dysfunction | Global longitudinal strain | All patients received both active and sham transcutaneous vagus nerve stimulation, with the order being randomized. The comparison is between active and sham stimulation. | Posted | Mean | Standard Deviation | percent | after 1 hour of stimulation |
|
through study completion (1 week)
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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 | Sham Intervention | Transcutaneous vagus nerve stimulation delivered at the earlobe (vagal innervation) is given on first session. Sham stimulation delivered at the tragus (devoid of vagal innervation) is given on second session. transcutaneous vagus nerve stimulation: All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Stavros Stavrakis | University of Oklahoma Health Sciences Center | 405-271-4742 | 37507 | stavros-stavrakis@ouhsc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Nov 17, 2017 | Apr 19, 2019 | ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 10, 2017 | Apr 19, 2019 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D054144 | Heart Failure, Diastolic |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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Transcutaneous vagus nerve stimulation delivered at the earlobe (vagal innervation) is given on first session. Sham stimulation delivered at the tragus (devoid of vagal innervation) is given on second session. transcutaneous vagus nerve stimulation: All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized |
|
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| Secondary | Heart Rate Variability Measures | low frequency to high frequency ratio. This is a measure of sympathovagal balance. A lower value reflects a more favorable balance between sympathetic and parasympathetic (vagal) tone. | All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized. The comparison is between active and sham stimulation. | Posted | Mean | Standard Deviation | ratio | after 1 hour of stimulation |
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| 0 |
| 24 |
| 0 |
| 24 |
| 0 |
| 24 |
| EG001 | Active Intervention | Transcutaneous vagus nerve stimulation delivered at the earlobe (vagal innervation) is given on first session. Sham stimulation delivered at the tragus (devoid of vagal innervation) is given on second session. transcutaneous vagus nerve stimulation: All patients will receive both active and sham transcutaneous vagus nerve stimulation, with the order being randomized | 0 | 24 | 0 | 24 | 0 | 24 |
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