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

Not Applicable

Not yet recruiting

• Conditions: Functional Dyspepsia
• Interventions: Device: taVNS; Behavioral: CBT; Behavioral: Education Control; Device: Sham taVNS

• Registration Number: NCT06360900
• Lead Sponsor: Spaulding Rehabilitation Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-03
• Study First Submitted QC: 2024-04-08
• Study First Posted: 2024-04-11
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-21
• Last Update Posted: 2025-03-26
• Study Start: 2025-06
• Primary Completion: 2029-03
• Study Completion: 2029-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Active taVNS + CBT	CBT	-
Active taVNS + Education Control	taVNS	-
Active taVNS + Education Control	Education Control	-
Sham taVNS + CBT	CBT	-
Sham taVNS + CBT	Sham taVNS	-
Active taVNS + CBT	taVNS	-
Sham taVNS + Education Control	Sham taVNS	-
Sham taVNS + Education Control	Education Control	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Gastric peristaltic velocity	8 weeks (post-treatment)	MRI-derived gastric motility outcome