Clinical trial NCT03327649: Neuromodulation to Treat Patients With Heart Failure With Preserved Ejection Fraction
Official title: Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure With Normal Ejection Fraction
Keywords: heart failure with preserved ejection fraction
inflammation
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
First posted: 2017-10-31
Enrollment: 52
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Heart failure with preserved ejection fraction (HFpEF) is a leading cause of mortality in the elderly. Outcomes of patients with HFpEF are poor and so far, no treatment has been shown to decrease morbidity or mortality. Recent animal and human studies suggest that a systemic proinflammatory state, produced by comorbidities, including aging, plays a central role in the development of HFpEF, supporting the notion that attenuating the proinflammatory state is an attractive therapeutic target for HFpEF. We have previously shown that low-level transcutaneous electrical stimulation of the vagus nerve (tVNS) suppresses inflammation in patients with atrial fibrillation. The overall objective of this proposal is to examine the effects of tVNS on diastolic dysfunction, exercise capacity and inflammation in patients with HFpEF. Our specific aims include: 1. To examine the effect of intermittent (1 hour daily for 3 months) tVNS on diastolic dysfunction and exercise capacity, relative to sham stimulation, in patients with HFpEF and 2. To examine the effect of intermittent (1 hour daily for 3 months) LLTS on inflammatory cytokines relative to sham stimulation, in patients with HFpEF. The proposed proof-of-concept studies will provide the basis for the design of further human studies using LLTS among populations with HFpEF. In light of the increasing number of elderly patients with HFpEF and the poor success of the currently available treatment options, an alternative and novel approach such as tVNS has the potential to impact clinical practice and improve health outcomes among a large number of patients. It is anticipated that these investigations will contribute to the broader understanding of the role of inflammation in the pathogenesis of HFpEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of inflammation affects one of the hallmarks of HFpEF, diastolic dysfunction, will lead to the development of novel pharmacological and non-pharmacological approaches to treat this disease.


Eligibility criteria: Inclusion Criteria:

* HFpEF, defined as signs and symptoms of heart failure, LV ejection fraction ≥50%, brain natriuretic peptide ≥35pg/mL and echocardiographic evidence of diastolic dysfunction (left atrial volume index ≥34mL/m2, mitral E-wave velocity/mitral annular velocity ratio \[E/e'\]≥13 and e'\<9cm/s) plus 2 of the following 4 comorbidities:

  * age ≥ 65,
  * diabetes,
  * hypertension and
  * obesity, defined as body mass index ≥30kg/m2

Exclusion Criteria:

* LV ejection fraction \<40%
* significant valvular disorder (i.e., prosthetic valve or hemodynamically significant valvular diseases)
* recent (\<6 months) stroke, myocardial infarction or hospitalization for heart failure
* severe heart failure (class III or IV)
* end stage kidney disease
* recurrent vasovagal syncope
* history of vagotomy
* pregnancy
* sick sinus syndrome and 2nd or 3rd degree AV block (without a pacemaker).

Primary outcomes:
measure: E/e' (Early Mitral Inflow Doppler Velocity to the Early Diastolic Mitral Annulus Velocity)
timeFrame: 3 months
measure: Global Longitudinal Strain
timeFrame: 3 months
Secondary outcomes:
measure: Exercise Capacity
timeFrame: 3 months
measure: Inflammatory Cytokines
timeFrame: 3 months
measure: Minnesota Living With Heart Failure Questionnaire
timeFrame: 3 months
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Stavros Stavrakis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stavrakis S, Elkholey K, Morris L, Niewiadomska M, Asad ZUA, Humphrey MB. Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction: A Pilot Randomized Clinical Trial. J Am Heart Assoc. 2022 Feb;11(3):e023582. doi: 10.1161/JAHA.121.023582. Epub 2022 Jan 13.