Synergistic Gut-brain Axis Modulation Via Vagal Stimulation and Cognitive Behavioral Therapy in Functional Dyspepsia

The primary aims of this randomized, single-blinded, 2x2 sham-controlled trial are to 1) evaluate synergistic impact of 8-weeks of transcutaneous auricular vagus nerve stimulation (taVNS) + cognitive-behavioral therapy (CBT) on post-meal gut-brain communication; 2) determine the sequential relationship between treatment-associated changes in gastrointestinal-related anxiety and both clinical functional dyspepsia (FD) improvements and meal-induced physiological outcomes; 3) investigate whether post-treatment changes in gut-brain physiology mediate improvements in FD clinical outcomes. Using a fully non-invasive framework including gastric and brain magnetic resonance imaging (MRI) and taVNS, the investigators aim to evaluate the potential synergy of taVNS and CBT in FD, by assessing the gut-brain physiological response to prandial challenge, linking physiological with symptom improvements.

Study Overview

• Status: Not yet recruiting
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Behavioral: CBT; Device: taVNS; Behavioral: Education Control; Device: Sham taVNS

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrew Bolender, BA; Phone Number: 617-643-4297; Email: abolender@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age 18-65 years old (inclusive)

• Ability to give written consent and participate in behavioral intervention in English
• Willingness to attend weekly treatment sessions over live video, daily self-administered transcutaneous auricular vagus nerve stimulation (taVNS) sessions, and engage in homework during treatment
• Avoidance of alcohol, nicotine, and caffeine for 24 hours prior to study session
• Diagnosis according to the Rome IV criteria for both epigastric pain syndrome and postprandial distress syndrome subtypes
• Stable medical treatment for functional dyspepsia (FD) during 1 month before the study and during the study period

Exclusion Criteria:

• Previous receipt of cognitive behavioral therapy (CBT) for gastrointestinal symptoms
• Enteral or parenteral feeding
• Previous gastrointestinal surgery, electrolyte disturbances, kidney dysfunction, renal insufficiency, or iron overload disorders
• Estimated Glomerular Filtration Rate (eGFR) < 60
• Medications that affect gastrointestinal motility in addition to medications or products containing tetrahydrocannabinol (THC) will be stopped at least 7 days prior to the start of the study and for the duration of the study. However, anti-depressants (SSRI's, TCA's) may be allowed in order to reduce the risk of worsening neuropsychiatric disease, though it will be up to the study team and the Principal Investigator whether subjects on anti-depressants will be able to participate in the study
• Intellectual disability by history
• Diabetes, mitochondrial disease, severe autonomic dysfunction, and small fiber polyneuropathy
• No active clinical acupuncture therapy
• Illicit drugs or opioid usage
• History of arrhythmias
• Current pregnancy/breastfeeding
• Contraindications for magnetic resonance imaging (MRI) (implanted ferromagnetic objects, claustrophobia)
• Weight > 450 lbs. (limit of the MRI table)
• Allergy to pineapple (used in the test meal during MRI)
• Any other condition interfering with study requirements, according to the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active taVNS + CBT	Behavioral: CBT; Cognitive Behavioral Therapy; Device: taVNS; Electrical transcutaneous auricular vagus nerve stimulation
Active Comparator: Active taVNS + Education Control	Device: taVNS; Electrical transcutaneous auricular vagus nerve stimulation; Behavioral: Education Control; Education of FD condition
Active Comparator: Sham taVNS + CBT	Behavioral: CBT; Cognitive Behavioral Therapy; Device: Sham taVNS; Sham (no current) transcutaneous auricular vagus nerve stimulation
Sham Comparator: Sham taVNS + Education Control	Behavioral: Education Control; Education of FD condition; Device: Sham taVNS; Sham (no current) transcutaneous auricular vagus nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nepean Dyspepsia Index (NDI)	FD symptoms severity; score ranging from 0 to 100, with higher scores indicating worse outcomes	8 weeks (post-treatment)
Visceral Sensitivity Index (VSI)	GI-related anxiety; score ranging from score ranging from 0 to 75, with higher scores indicating worse outcomes	8 weeks (post-treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric peristaltic velocity	MRI-derived gastric motility outcome	8 weeks (post-treatment)

Collaborators and Investigators

• Sponsor: Spaulding Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: April 3, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia
• Other Study ID Numbers: 2024P000849

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No