Heart failure (HF) is the leading cause of death in US. It is associated with abnormal vascular function termed endothelial dysfunction. It is also associated with increased stress on the blood vessels and high levels of inflammation. Vagus nerve stimulation can help improve inflammation, vascular function and vascular stress. The investigator has recently completed a study showing that 1 hour of noninvasive vagus stimulation can improve vascular health. However, it is unknown if 4 weeks of stimulation will be beneficial in systolic heart failure.
The purpose of this study is to determine if transcutaneous vagal stimulation (TVS) will lead to improvement in the function of the inner lining of participants' arteries, memory, and in the levels of certain chemical markers of arterial function in the blood.
Participants will be randomized to receive either TVS or a sham stimulation and undergo 4 weeks of stimulation. Vascular function will be assessed by several non-invasive measurements, including Flow Mediate Dilation (FMD), Pulse Wave Analysis (PWA), EndoPAT, and Laser Speckle Contrast Imaging (LSCI). Participants' memory will also be measured through electronic assessments and blood will be collected and analyzed for arterial function chemical markers.
Condition or disease | Intervention/treatment | Phase |
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Heart Failure With Reduced Ejection Fraction | Device: TVS Device: SHAM | Not Applicable |
Visit 1: Following tests(to assess vascular function) will be done: 1. FMD 2) LSCI 3) EndoPAT and 4) Pulse wave analysis (PWA). Patients will rest for 10 minutes between each test. They will be trained to use PARASYMTM unit for TVS. Blood collected, serum/plasma will be stored at -80F. Whole blood will be collected in PAXgene tubes. Patients will be instructed to apply TVS to either ear lobule (SHAM) or Tragus(experimental arm). Baseline characteristics will be collected including data on ventricular function(LVEF and left ventricular volumes).
Visit 2 (4 weeks): Follow up tests(FMD,LSCI,EndoPAT,PWA) and repeat blood collection.
Inflammatory cytokines and vascular function assays will be performed.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 50 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Effect of Neuromodulation on Inflammation, Endothelial Function and Cognitive Dysfunction in Patients With Heart Failure With Reduced Ejection Fraction |
Actual Study Start Date : | February 4, 2020 |
Estimated Primary Completion Date : | May 1, 2021 |
Estimated Study Completion Date : | May 1, 2021 |
Arm | Intervention/treatment |
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Experimental: Experimental
Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 4 weeks.
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Device: TVS
Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 4 weeks
Device: SHAM Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the earl lobule. Stimulator will be applied continuously for 1 hour daily for 4 weeks.
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Sham Comparator: CONTROL
Sham TVS will be performed by use of a Tragus stimulator device with electrodes attached to the ear lobule. Stimulator will be applied continuously for 1 hour daily for 4weeks.
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Device: TVS
Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the tragus of the ear. Stimulator will be applied continuously for 1 hour daily for 4 weeks
Device: SHAM Active TVS will be performed by use of a Tragus stimulator device with electrodes attached to the earl lobule. Stimulator will be applied continuously for 1 hour daily for 4 weeks.
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Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
1. Patients (18 years or older) with Heart failure with reduced ejection fraction (HFrEF), which is a history of symptomatic heart failure with left ventricular ejection fraction (LVEF) of < 40%.
Exclusion Criteria:
Contact: Tarun Dasari, MD | 4052714742 ext 44754 | tdasari@ouhsc.edu |
United States, Oklahoma | |
University of Oklahoma Health Sciences Center | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
Contact: Tarun Dasari, MD 405-271-8001 ext 44754 tarun-dasari@ouhsc.edu | |
Principal Investigator: Tarun Dasari, MD |
Principal Investigator: | Taun Dasari, MD | OUHSC |
Tracking Information | |||||||
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First Submitted Date ICMJE | March 15, 2019 | ||||||
First Posted Date ICMJE | May 10, 2019 | ||||||
Last Update Posted Date | December 21, 2020 | ||||||
Actual Study Start Date ICMJE | February 4, 2020 | ||||||
Estimated Primary Completion Date | May 1, 2021 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||||
Current Secondary Outcome Measures ICMJE |
Cognition [ Time Frame: Change in the cognition score , as assessed by the CANTAB method will be compared at baseline and after 4 weeks of TVS or sham stimulation. ] Cognition score(%) calculated from Cambridge Neuropsychological Test Automated Battery -CANTAB method . This will be done using a hand held ipad.
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Original Secondary Outcome Measures ICMJE |
Cognition [ Time Frame: Change in the cognition score , as assessed by the CANTAB method will be compared at baseline and after 8 weeks of TVS or sham stimulation. ] Cognition score(%) calculated from Cambridge Neuropsychological Test Automated Battery -CANTAB method . This will be done using a hand held ipad.
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Neuromodulation of Inflammation and Vascular Function in Systolic Heart Failure | ||||||
Official Title ICMJE | Effect of Neuromodulation on Inflammation, Endothelial Function and Cognitive Dysfunction in Patients With Heart Failure With Reduced Ejection Fraction | ||||||
Brief Summary |
Heart failure (HF) is the leading cause of death in US. It is associated with abnormal vascular function termed endothelial dysfunction. It is also associated with increased stress on the blood vessels and high levels of inflammation. Vagus nerve stimulation can help improve inflammation, vascular function and vascular stress. The investigator has recently completed a study showing that 1 hour of noninvasive vagus stimulation can improve vascular health. However, it is unknown if 4 weeks of stimulation will be beneficial in systolic heart failure. The purpose of this study is to determine if transcutaneous vagal stimulation (TVS) will lead to improvement in the function of the inner lining of participants' arteries, memory, and in the levels of certain chemical markers of arterial function in the blood. Participants will be randomized to receive either TVS or a sham stimulation and undergo 4 weeks of stimulation. Vascular function will be assessed by several non-invasive measurements, including Flow Mediate Dilation (FMD), Pulse Wave Analysis (PWA), EndoPAT, and Laser Speckle Contrast Imaging (LSCI). Participants' memory will also be measured through electronic assessments and blood will be collected and analyzed for arterial function chemical markers. |
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Detailed Description |
Visit 1: Following tests(to assess vascular function) will be done: 1. FMD 2) LSCI 3) EndoPAT and 4) Pulse wave analysis (PWA). Patients will rest for 10 minutes between each test. They will be trained to use PARASYMTM unit for TVS. Blood collected, serum/plasma will be stored at -80F. Whole blood will be collected in PAXgene tubes. Patients will be instructed to apply TVS to either ear lobule (SHAM) or Tragus(experimental arm). Baseline characteristics will be collected including data on ventricular function(LVEF and left ventricular volumes). Visit 2 (4 weeks): Follow up tests(FMD,LSCI,EndoPAT,PWA) and repeat blood collection. Inflammatory cytokines and vascular function assays will be performed. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Not Applicable | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Heart Failure With Reduced Ejection Fraction | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
50 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | May 1, 2021 | ||||||
Estimated Primary Completion Date | May 1, 2021 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria: 1. Patients (18 years or older) with Heart failure with reduced ejection fraction (HFrEF), which is a history of symptomatic heart failure with left ventricular ejection fraction (LVEF) of < 40%. Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 85 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03945058 | ||||||
Other Study ID Numbers ICMJE | 10410 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | University of Oklahoma | ||||||
Study Sponsor ICMJE | University of Oklahoma | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | University of Oklahoma | ||||||
Verification Date | December 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |