- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03715543
Surgical Resection of the Greater Splanchnic Nerve in Subjects Having Heart Failure With Preserved Ejection Fraction
Surgical Resection of the Greater Splanchnic Nerve in Subjects Having Heart Failure With Preserved Ejection Fraction: First-in-human Feasibility Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
Heart failure (HF) is a major and growing public health problem with more than 5 million identified cases and an incidence of over 600,000 new cases per year in the United States alone. Close to 1 million hospitalizations for heart failure occur annually, accounting for over 6.5 million hospital days and a substantial portion of the estimated $37.2 billion that is spent each year on HF in the United States. Nearly half of all patients with HF have so called heart failure with preserved ejection fraction (HFpEF). The 5-year mortality for HFpEF has been reported as high as 50-65%. There are no current evidenced-based HFpEF therapies beyond diuretic control for fluid overload and standard treatments for comorbidities, making HFpEF an exemplary example of an unmet medical need of a rising societal burden and that is associated with substantial morbidity and mortality.
In HFpEF, sympathetic nervous system (SNS) hyperactivity results in decreased splanchnic capacitance causing more blood to be distributed into the central venous and arterial system. This leads to increase central venous pressure, pulmonary pressures and right/left heart pressures, which ultimately results in: congestions, diuretic resistance, acute decompensations leading to rehospitalization, dyspnea and intolerance to even mild exercise, and progressive diastolic dysfunction.
We believe that blocking of the GSN will stop SNS activity from reaching the splanchnic vessels and result in a redistribution of blood volume back into the splanchnic reservoir, which will result in reduction of central venous, pulmonary and right and left heart pressures. For patients with HFpEF we expect these changes to improve dyspnea and capacity to exercise, improve quality of life, increased diuretic responsiveness, Furthermore, the expected benefits of unloading the central venous and arterial system through GSN ablation should improve hemodynamic control and lessen the incidence and severity of acute decompensations leading to reduced re-hospitalizations and associated healthcare costs. This has the potential for significant social and healthcare impact.
Sympathetic and parasympathetic innervation is carried to the upper abdominal viscera by the GSN, lesser splanchnic nerve (LSN) and least splanchnic nerve (LTSN), which originate from the 5th to 8th, 9th to 10th, and 11th thoracic ganglia, respectively.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adult patients ≥ 18 years of age with guideline defined HFpEF class III/IV (EF>40% on optimal medical therapy)
- History of exertion-related dyspnea in last 3 months
- No evidence of clinically significant peripheral edema/fluid overload
- Resting PCWP or PAD > 15 mmHg or > 25 mmHg during exercise
- The ability understand and provide signed informed consent
Exclusion Criteria:
- Myocardial infarction and/or percutaneous cardiac intervention within past 3 months; coronary artery bypass graft in past 3 months or current indication for coronary revascularization
- Admission for HF within the past month
- Systolic Blood Pressure (BP) < 120 mmHg or > 170 mmHg despite appropriate medical management
- Inability to perform Cardio Pulmonary Exercise Test (CPET)
- Presence of severe regurgitant or stenotic valve disease
- Atrial fibrillation with resting heart rate >100 beats/min
- Arterial oxygen saturation < 90 % on room air
- Significant hepatic impairment, defined as 3× upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
- Known pre-existing severe pulmonary hypertension
- Chronic pulmonary disease requiring home O2, hospitalization for exacerbation within 6 months before study entry, or on chronic steroids
- Life expectancy <12 months for non-cardiovascular reasons
- Women of childbearing age
- Currently requiring dialysis or estimated glomerular filtration rate < 40 mL/min/1.73m2
- Patients who have had cardiac transplantation or maybe considered for heart transplant
- Currently participating in an investigational drug or device study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered to be investigational trials
- Chronic or parenteral anticoagulation drug use without ability to hold for at least 72 hours
- In the opinion of the investigator, the subject is not an appropriate candidate for the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Surgical Resection Arm
Surgical Resection of the Greater Splanchnic Nerve
|
Video-Assisted Thoracoscopic Surgery (VATS) is performed under general anesthesia using existing, CE marked instrumentation. Two or more 5 mm incisions are used to pass a tiny video camera and a single dissecting instrument into the chest. These small ports are advantageous because the chance for infection and wound dehiscence are drastically reduced. This allows for a faster recovery by the patient and a greater chance for the wound to heal. In the procedure the GSN will be identified visually or through stimulation-induced hemodynamic reflex. The GSN will then be ablated using standard techniques. If there are multiple branches of the GSN, each branch will be systematically identified and ablated. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Blunting or delay in rise of Pulmonary Capillary Wedge Pressure (PWCP) or Pulmonary Artery Diastolic Pressure (PAD) during exercise
Time Frame: at 1 month post-procedure as compared to baseline
|
at 1 month post-procedure as compared to baseline
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Reduction in resting Pulmonary Capillary Wedge Pressure (PWCP) or Pulmonary Artery Diastolic Pressure (PAD)
Time Frame: at 1 and 3 months post-procedure
|
at 1 and 3 months post-procedure
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GSN FIH Study
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Heart Failure With Preserved Ejection Fraction
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University of SienaEuropean Association of Cardiovascular ImagingActive, not recruitingHeart Failure | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection Fraction | Heart Failure With Mid Range Ejection FractionSpain, Greece, Turkey, Portugal, Australia, Belgium, Italy, Mexico, Netherlands, North Macedonia, Romania, Tunisia
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University Hospital, AkershusNovartisActive, not recruitingHeart Failure | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection FractionNorway
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Istituti Clinici Scientifici Maugeri SpARecruitingHeart Failure With Preserved Ejection Fraction | Heart Failure With Midrange Ejection FractionItaly
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Milton S. Hershey Medical CenterWithdrawnHeart Failure | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection FractionUnited States
-
Board of Trustees of Illinois State UniversityUniversity of Colorado, Denver; Abbott; University of North Carolina, Greensboro and other collaboratorsRecruitingHeart Failure | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection FractionUnited States
-
Milton S. Hershey Medical CenterCompletedHeart Failure | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection FractionUnited States
-
Zhijun SunEnrolling by invitationHeart Failure | Heart Failure With Preserved Ejection Fraction | Heart Failure With Mid Range Ejection FractionChina
-
Corvia MedicalWithdrawnHeart Failure With Preserved Ejection Fraction | Heart Failure With Mid Range Ejection Fraction
-
Occlutech International ABActive, not recruitingHeart Failure With Preserved Ejection Fraction (HFpEF) | Heart Failure With Reduced Ejection Fraction (HFrEF)United States
-
Yale UniversityRecruitingHeart Failure | Heart Failure With Reduced Ejection Fraction | Heart Failure With Preserved Ejection Fraction | Heart Failure NYHA Class IVUnited States
Clinical Trials on Surgical Resection of the Greater Splanchnic Nerve
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Karolinska InstitutetCompleted
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Qazvin University Of Medical SciencesUnknownOral Lichen PlanusIran, Islamic Republic of
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Ozge Surmeli OnayEskisehir Osmangazi UniversityCompletedFeeding Patterns | Intrauterine Growth Retardation | Splanchnic HypoperfusionTurkey
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Helwan UniversityCompletedBenign Prostatic HyperplasiaEgypt
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Hopital de l'Enfant-JesusUnknown
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Sun Yat-sen UniversityUnknownColorectal Cancer MetastaticChina
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NoblewellCompletedSystolic Heart Failure | Peripheral Chemoreceptor HypersensitivityPoland
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University of Texas Southwestern Medical CenterRecruitingBrain MassUnited States
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University Hospital, RouenUnknownResectable Non-small Lung CancerFrance