# Synergistic gut-brain axis modulation via vagal stimulation and cognitive behavioral therapy in functional dyspepsia

> **NIH NIH R01** · SPAULDING REHABILITATION HOSPITAL · 2024 · $747,247

## Abstract

PROJECT SUMMARY/ABSTRACT
Functional dyspepsia (FD) is one of the most common disorders of gut-brain interaction (DGBI), characterized
by 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. Despite the high
prevalence, there is a lack of treatment options available to patients for whom traditional pharmacological
interventions have failed due to either lack of efficacy or uncontrollable side effects. While many non-
pharmacological therapies have shown promise for DGBI, including FD, the efficacy of any single-modality
treatment is typically modest. Finding a way to boost clinical outcomes for these therapeutic modalities is a
crucially important goal. As FD is a multifactorial condition with visceral, affective, and cognitive components,
we propose that multimodal neurophysiologically-informed strategies – e.g. combining bottom-up and top-down
approaches - will enhance benefits by targeting different, but convergent, neural pathways that contribute to
FD symptomatology. To date, however, better integration of bottom-up and top-down strategies has been
hampered by a lack of mechanistic understanding of how they interact to improve FD symptoms, presenting a
knowledge gap that, when filled, could help optimize care by illuminating approaches that are most likely to
have a synergistic salubrious effect. Specifically, we propose a randomized, single-blinded, 2x2 sham-
controlled trial to investigate the potential synergy of transcutaneous auricular vagus nerve stimulation (taVNS,
bottom-up) with GI-targeted cognitive-behavioral therapy (GI-CBT, top-down). We will evaluate the longitudinal
effects (8 weeks) of taVNS+CBT (or controls) on post-meal gut-brain physiology and clinical outcomes.
Furthermore, we will examine the role of GI-specific anxiety in anticipating (i.e. change at 4 weeks) and thus
predicting clinical improvements following 8 weeks of therapy, as well as mediating post-therapy changes in
gut-brain physiology and clinical outcomes. In our study, we will exploit our fully non-invasive experimental
framework including sequential gastric and brain Magnetic Resonance Imaging (MRI). The significance of our
proposal is high as it will provide a mechanistic framework for how taVNS and CBT, both separately and
synergistically, modulate FD pathophysiology, leading to future clinical trials to evaluate this integrated
multimodal intervention for difficult to treat chronic GI disorders, such as FD.

## Key facts

- **NIH application ID:** 10801506
- **Project number:** 1R01DK136243-01A1
- **Recipient organization:** SPAULDING REHABILITATION HOSPITAL
- **Principal Investigator:** Roberta Sclocco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,247
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801506

## Citation

> US National Institutes of Health, RePORTER application 10801506, Synergistic gut-brain axis modulation via vagal stimulation and cognitive behavioral therapy in functional dyspepsia (1R01DK136243-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10801506. Licensed CC0.

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