Cortical Excitability in Cyclic Vomiting Syndrome

This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome (CVS) and healthy control subjects, as assessed by a non-invasive method of brain stimulation (Transcranial Magnetic Stimulation, TMS).

Study Overview

• Status: Recruiting
• Conditions: Cyclic Vomiting Syndrome
• Intervention / Treatment: Other: TMS Paired-Pulse assessment of cortical excitability; Other: Autonomic activity

Detailed Description

This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome (CVS) and healthy control subjects, as assessed by a non-invasive method of brain stimulation (Transcranial Magnetic Stimulation, TMS).

Using the paired-pulse TMS paradigm, intracortical inhibition and facilitation of cortical circuitry will be assessed by stimulating the motor cortex and using the electromyographic (EMG) response of a target muscle as readout. In such studies, a conditioning stimulus modulates the amplitude of the motor-evoked potential (MEP) produced by the test stimulus. Depending on the inter-stimulus interval, effects can be attributed to different aspects of cortical processing. Brief intervals (1-5 ms) will be used to assess short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF), intermediate intervals (7-20 ms) to assess intracortical facilitation (ICF) and long intervals (50-200 ms) to assess long-interval intracortical inhibition (LICI).

Some clinical, demographic, and autonomic data (i.e. EKG) will be recorded and used as covariates to investigate any systematic impact on cortical excitability measures collected with the paired-pulse protocols.

• Study Type: Interventional
• Enrollment (Estimated): 110
• 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: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• diagnosis of CVS

Exclusion Criteria:

• history of CVS (for healthy control population only)
• psychosis or altered cognitive status
• history of head injury, metal in the skull, stroke, or a history of seizures or a history of syncope (fainting or passing out)
• implantable devices, such as a pacemaker or nerve stimulator
• current use of the following medications or use of substances which are known to lower the seizure threshold: clozapine (Clozaril), chlorpromazine (Thorazine), amphetamines or methamphetamine, Ecstasy, Ketamine, Angel Dust/PCP, cocaine, or 3 or more alcoholic drinks per day
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CVS subjects; Subjects diagnosed with Cyclic Vomiting Syndrome (CVS)	Other: TMS Paired-Pulse assessment of cortical excitability; Using the paired-pulse TMS paradigm, intracortical inhibition and facilitation of cortical circuitry will be assessed by stimulating the motor cortex and using the electromyographic (EMG) response of a target muscle as readout. In such studies, a conditioning stimulus modulates the amplitude of the motor-evoked potential (MEP) produced by the test stimulus. Depending on the inter-stimulus interval, effects can be attributed to different aspects of cortical processing. Brief intervals (1-5 ms) will be used to assess short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF), intermediate intervals (7-20 ms) to assess intracortical facilitation (ICF) and long intervals (50-200 ms) to assess long-interval intracortical inhibition (LICI).; Other: Autonomic activity; Autonomic function will be determined using continuously recorded EKG and used as covariates to investigate any systematic impact on cortical excitability measures collected with the paired-pulse protocols.
Active Comparator: healthy, non-CVS subjects; Subjects not diagnosed with CVS	Other: TMS Paired-Pulse assessment of cortical excitability; Using the paired-pulse TMS paradigm, intracortical inhibition and facilitation of cortical circuitry will be assessed by stimulating the motor cortex and using the electromyographic (EMG) response of a target muscle as readout. In such studies, a conditioning stimulus modulates the amplitude of the motor-evoked potential (MEP) produced by the test stimulus. Depending on the inter-stimulus interval, effects can be attributed to different aspects of cortical processing. Brief intervals (1-5 ms) will be used to assess short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF), intermediate intervals (7-20 ms) to assess intracortical facilitation (ICF) and long intervals (50-200 ms) to assess long-interval intracortical inhibition (LICI).; Other: Autonomic activity; Autonomic function will be determined using continuously recorded EKG and used as covariates to investigate any systematic impact on cortical excitability measures collected with the paired-pulse protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paired-pulse ratios	Percentage Change in Paired Pulse (PP) TMS induced MEP responses with inhibitory or facilitatory stimulation.	Multiple study sessions spanning up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TMS motor threshold	TMS stimulator output necessary to elicit 200 microvolt MEP responses	Multiple study sessions spanning up to 12 months
Cortical silent period	Length (milliseconds) of EMG inactivity following TMS stimulation	Multiple study sessions spanning up to 12 months
Heart rate variability	Spectral frequency analysis (via Fast Fourier Transformation) of R-R intervals	Multiple study sessions spanning up to 12 months

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: David J Levinthal, MD PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: February 15, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Signs and Symptoms, Digestive; Disease; Syndrome; Vomiting
• Other Study ID Numbers: STUDY21120001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no current plan to place participant data into a open-access, shared data repository. However, a data sharing agreement can be made if requested.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No