Cerebral Cortical Influences on Autonomic Function

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions

Functional Dyspepsia
Healthy Subjects
Irritable Bowel Syndrome

Type

Interventional

Phase

Not Applicable

Design

Allocation: Non-RandomizedIntervention Model: Factorial AssignmentIntervention Model Description: Subjects will act as their own controls: The investigators will assess measures of autonomic function at baseline and in response to rTMS exposure (with or without study medication) in three groups of subjects: 1) subjects without history of gastrointestinal disease, 2) subjects with Irritable Bowel Syndrome, and 3) subjects with Functional Dyspepsia.Masking: None (Open Label)Primary Purpose: Basic Science

Participation Requirements

Age: Between 18 years and 75 years
Gender: Both males and females

Description

The overall goal of this study is to determine the impact of non-invasive brain stimulation on autonomic function in human subjects without functional gastrointestinal disorders and in subjects with Irritable Bowel Syndrome (IBS) or Functional Dyspepsia (FD). Aim 1: Determine whether repetitive transcranial magnetic stimulation (rTMS) of specific cortical areas alters physiologic measures of gastrointestinal and cardiac function. The investigators will use rTMS to transiently induce changes in neural excitability within specific cortical regions identified as being linked to autonomic regulation. Based on preliminary neuroanatomical data, one of the leading candidate cortical areas associated with sympathetic regulation lies within the trunk representation of the primary motor cortex. Thus, the investigators first plan on targeting this region of the primary motor cortex with rTMS and assess the effect of various parameters of rTMS on gastrointestinal and cardiac function in healthy human subjects. The investigators will then perform additional experiments using rTMS targeted to other specific cortical sites, such as the dorsal premotor area and rostral cingulate cortex that have also been linked to autonomic control. Each of these identified cortical regions may make unique contributions to autonomic reactivity. Aim 2: Determine whether the effects of targeted rTMS on autonomic function are mediated through a specific branch of the autonomic nervous system. In different sessions, the investigators will use FDA-approved pharmacological agents (hyoscyamine and metoprolol) to help determine whether the observed autonomic effects of cortical TMS are mediated primarily through the sympathetic or parasympathetic branches of the autonomic nervous system. Aim 3: Determine whether patients with functional gastrointestinal disorders demonstrate altered physiological reactivity to targeted rTMS. The investigators will use the optimal parameters of rTMS and regions of interest determined in Aim 1 to assess the gastrointestinal and cardiac reactivity in participants with functional dyspepsia (FD) and/or irritable bowel syndrome (IBS). These physiological responses will be correlated with assessments of disease severity, mood, and quality of life. In different sessions, the investigators will use FDA-approved pharmacological agents (hyoscyamine and metoprolol) to help determine whether any observed differences in physiological reactivity to targeted rTMS are primarily mediated through sympathetic or parasympathetic control.

Tracking Information

NCT #: NCT03869372
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators: Principal Investigator: David J Levinthal, MD/PhD University of Pittsburgh