Functional Dyspepsia (FD) is a common functional gastrointestinal disorder that affects millions of Americans every year. Symptoms include recurrent epigastric discomfort consisting of any one or a combination of postprandial fullness, early satiation, and/or epigastric pain or burning, in the absence of a clear structural etiology. Some patients with FD are particularly bothered by postprandial fullness and early satiation, a hallmark of the Postprandial Distress Syndrome (PDS) subtype. These symptoms can be particularly debilitating, leading to impaired daily functioning and decreased quality of life. Despite the negative impact these symptoms have on patients' lives, the pathogenesis of PDS-predominant FD (PDS-FD) is not well understood, although it has been postulated that dysregulation of the brain-gut axis driven by abnormal brainstem vagal neurocircuitry is a possible culprit. The current mainstay of treatment for PDS-FD is pharmacological intervention which is, at best, modestly effective. Moreover, in some severe cases, symptoms become intractable, medication causes unwanted side effects and/or patient becomes treatment resistant. However, given the strong link between FD symptoms and compromised vagal function we propose a non- invasive approach that targets the auricular branch of the vagus nerve via transcutaneous vagal nerve stimulation (tVNS) delivered to the cymba conchae of the external ear. Thus, auricular tVNS may provide a novel therapeutic strategy to modulate aberrant brain-gut signaling in PDS-predominant FD. In the current project, we use gastric/autonomic measures combined with multimodal neuroimaging techniques to interrogate the peripheral and central nervous system changes that accompany neuromodulation of brain-gut axis signaling by auricular tVNS in PDS-FD patients during a prandial challenge. The proposed study will contribute new insights into the pathophysiology underlying PDS-FD as well as evaluate the fidelity of novel, non-invasive neuromodulatory techniques such as auricular tVNS to mitigate FD symptoms.

Public Health Relevance

The primary aims of this single-blind, randomized, sham-controlled cross-over study are to 1) investigate the neuromodulatory effects of transcutaneous vagal nerve stimulation (tVNS) on aberrant brain-gut axis signaling using a liquid meal challenge to drive the symptomatic state in functional dyspepsia (FD) patients with postprandial distress syndrome (PDS) using combined gastric/autonomic and multimodal neuroimaging metrics, and 2) evaluate the effectiveness of tVNS, as a novel, non-invasive therapeutic strategy to mitigate abnormal brain-gut axis functioning in PDS-predominant FD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK116029-01
Application #
9433872
Study Section
Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
Program Officer
Unalp-Arida, Aynur
Project Start
2018-08-15
Project End
2020-07-31
Budget Start
2018-08-15
Budget End
2019-07-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114