Brain-Stomach Circuits in Chronic Nausea

TMS Neuromodulation of Brain-to-Stomach Circuits in Chronic Nausea

The goal of this study is to determine whether stimulation of the brain-stomach connection can influence stomach activity in healthy adults and in individuals suffering from chronic nausea. The main questions it aims to answer are:

• What are the best brain sites to influence the stomach?
• What are the effects of different stimulation patterns on stomach activity?
• Does the stimulation affect the sensation of nausea in participants suffering from chronic nausea?

Researchers will use a non-invasive method of brain stimulation called Transcranial Magnetic Stimulation (TMS) and will record stomach responses with skin electrodes on the abdomen.

Participants will:

• Visit the clinic at least once, and for up to 9 times more over the course of several months.
• Receive TMS while sitting in a chair similar to a dentist's chair.
• Drink water or consume a test meal during each study visit.

Study Overview

• Status: Recruiting
• Conditions: Chronic Nausea and Vomiting Syndrome
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation, TMS

Detailed Description

This study will use cutaneous recordings of stomach activity (electrogastrogram, EGG) and non-invasive brain stimulation with Transcranial Magnetic Stimulation (TMS) to

1. map descending cerebral cortical-to-stomach circuitry via gastric motor-evoked potentials (GMEPs),
2. use repetitive TMS (rTMS) applied to GMEP hotspots to modulate the stomach response to a satiety task (water load or nutrient drink/meal),
3. assess differences in topography and function of cortical-to-stomach circuitry between healthy subjects and subjects suffering from chronic nausea vomiting syndrome (CNVS).

Some clinical, demographic, and autonomic data (i.e. EKG) will be recorded and used as covariates to investigate any systematic impact on the outcome measures.

• Study Type: Interventional
• Enrollment (Estimated): 219
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paul HM Kullmann, PhD; Phone Number: 412-647-1533; Email: phmk@pitt.edu
• Study Contact Backup: Name: David J Levinthal, MD PhD; Phone Number: 412-303-0525; Email: levinthald@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults between ages 21-60 years old, with and without CNVS diagnosis per self-report.

Exclusion Criteria:

• body mass index (BMI) > 30
• pregnancy or intention to become pregnant
• past or present chemotherapy
• diagnosis of gastric (stomach) cancer
• any kind of gastric (stomach) surgery
• current use of GLP-1 receptor agonists (e.g. Ozempic, Trulicity)
• medications which significantly lower seizure thresholds (e.g. bupropion (Wellbutrin), fluoxetine (Prozac), or tramadol (Ultram))
• implantable devices, such as a pacemakers or nerve stimulators
• history of head injury that required hospitalization, metal in the skull, or neurologic disease such as stroke, history of seizures or history of syncope (fainting or passing out)
• neurodegenerative disease (Multiple Sclerosis, Parkinson's or Alzheimer's Disease)
• ongoing psychosis or altered cognitive status status (e.g. hearing sounds or seeing visions that are not there, or feeling confused or suffering from memory lapses)
• history of cardiovascular (i.e., heart attack), pulmonary (i.e., need for supplemental oxygen), or endocrine disease (e.g. diabetes)
• current enrollment in another study using Transcranial Magnetic Stimulation (TMS)
• current use of drugs such as amphetamines, methamphetamine, Ecstasy, Ketamine, Angel Dust/PCP, cocaine, or drinking 3 or more alcoholic drinks per day
• For healthy subjects only: chronic history of gastrointestinal symptoms (e.g., nausea, indigestion, bloating, abdominal pain)
• For CNVS subjects only: diagnosis of gastric motility disorder (e.g. gastroparesis/slow stomach emptying) or history of bowel obstruction (i.e., chronic partial small bowel obstruction)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Healthy subjects and CNVS subjects; Subjects without gastric problems and subjects with Chronic Nausea and Vomiting (CNVS)

Device: Transcranial Magnetic Stimulation, TMS; The best location for evoking an electromyographic (EMG) response of the first dorsal interosseus (FDI) muscle in left and right hand to stimulation of the primary (M1) motor cortex and the minimum stimulation intensity required to evoke a certain EMG response amplitude (Motor Threshold, MT) are determined. This serves as a reference to determine the best location and stimulation parameters to evoke GMEPs from M1 and pre-motor cortical areas. After identification of the GMEP hot-spot, a stomach filling task (water load test or test meal) is administered and changes in the electrogastrogram (EGG) are monitored. In subsequent study visits, the stomach filling task is preceded by application of neuromodulatory repetitive TMS (rTMS), targeted to the GMEP hotspot.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMEP location	Location of GMEP hotspot(s) in M1 and/or premotor areas relative to FDI hotspot	Baseline session
EGG power change	Change in spectral power of the EGG in the 3 cpm frequency band associated with the gastric filling task (water load or test meal), either followed or not by neuromodulatory rTMS	Each study session through study completion, up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMEP amplitude	Amplitude of GMEPs at hotspot	Each study session through study completion, up to 1 year
Volume	Volume consumed during the gastric filling task	Each study session through study completion, up to 1 year
Nausea severity (only participants suffering from chronic nausea)	Nausea severity rating on an 11-point (0-10) Likert-scale (0=none, 10=worst possible)	Each study session through study completion, up to 1 year

Collaborators and Investigators

• Sponsor: David Levinthal
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: David J Levinthal, MD PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Chronic unexplained nausea and vomiting
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Vomiting; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: STUDY25100001; 1R01DK144729 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Final analytic de-identified datasets will be deposited in the SPARC data repository.
• IPD Sharing Time Frame: Datasets will be deposited within 2 years of study completion for as long as the SPARC repository is active.
• IPD Sharing Access Criteria: The SPARC repository is publicly accessible.

Drug and device information, study documents

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