Cerebral Cortical Influences on Autonomic Function

David Levinthal

Status: Active, not recruiting

Conditions: Irritable Bowel Syndrome; Functional Dyspepsia; Healthy Subjects

Treatments: Device: rTMS

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03869372

STUDY19010027

5K08DK101756-05 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This is an exploratory neurophysiological study that will determine the impact of non-invasive brain stimulation on autonomic regulation, with a focus on gastrointestinal function. These studies should provide a basis for future brain-based neurotherapeutic strategies in patients with functional GI disorders.

Full 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 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.

--This study description has been revised since its original posting. Because all study procedures are performed in all subjects, regardless of being a healthy subject or one with FD and/or IBS, rather than a three arm trial, this trial should be regarded as having a single arm study design.

Enrollment: 244 estimated patients

Sex: All

Ages: 21 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults between age 21 and 60
• Participants without gastrointestinal symptoms (Healthy Subjects)
• Participants with gastrointestinal symptoms compatible with functional dyspepsia (FD) and or irritable bowel syndrome (IBS)

Exclusion criteria

• history of myocardial infarction, supplemental oxygen requirement, or diabetes
• history of chronic gastrointestinal symptoms (for healthy subjects only)
• history of gastric surgery
• psychosis or altered cognitive status
• history of head injury, metal in the skull, stroke, or a history of seizures
• 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: amitriptyline (Elavil), nortriptyline (Pamelor), imipramine (Tofranil), doxepin (Sinequan), clozapine (Clozaril), chlorpromazine (Thorazine), amphetamines or methamphetamine, Ecstasy, Ketamine, Angel Dust/phencyclidine (PCP), cocaine, or 3 or more alcoholic drinks per day
• pregnancy
• Body-Mass-Index (BMI) > 35

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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244 participants in 1 patient group

Study subjects

Experimental group

Description:

At the baseline session, measures of autonomic activity (electrogastrogram - EGG, electrocardiogram - ECG, cardiac impedance - CI) will be monitored from about 15 minutes before up to 1 hour after consumption of a test meal, water or a nutrient drink. In addition, motor-evoked potentials (MEPs) elicited with single pulse transcranial magnetic stimulation will be assessed before and after the meal or drink. In subsequent sessions, repetitive transcranial magnetic stimulation (rTMS) is applied before the meal or drink. Based on responses to symptom surveys (IBS-SSS and PAGI-SYM), study subjects will be characterized as healthy or as having functional dyspepsia and/or IBS.

Treatment:

Device: rTMS