Cerebral Cortical Influences on Autonomic Function

Healthy Subjects Clinical Trial

Official title:

Cerebral Cortical Influences on Autonomic Function

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03869372
• Other study ID #: STUDY19010027
• Secondary ID: 5K08DK101756-05
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 5, 2019
• Est. completion date: October 3, 2025

Study information

• Verified date: March 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 244
• Est. completion date: October 3, 2025
• Est. primary completion date: October 3, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Dyspepsia
• Functional Dyspepsia
• Healthy Subjects
• Irritable Bowel Syndrome

Intervention

Device:
• rTMS
In subsequent sessions, the same measures of autonomic activity and MEPs will be monitored but different patterns of repetitive TMS (rTMS) will be applied to motor cortex or other areas before the test meal, water or nutrient drink is consumed.

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
David Levinthal	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Electrogastrogram (EGG)	The EGG will be analyzed in the frequency domain using fast Fourier Transformation (FFT). The power spectrum will be divided into frequency bands (normal gastric activity (~3 cycles per minute), slower than normal (bradygastria) and faster than normal (tachygastria)). rTMS-induced shifts in the power distribution across these frequency bands after consumption of water or a nutrient drink or a test meal will be compared to water or nutrient drink or test meal without rTMS.	EGG will be monitored for 15 minutes before and up to 1 hour after consumption of the nutrient drink or the test meal
Primary	Volume threshold to satiety	rTMS-induced shift in the volume of water or nutrient drink a subject can consume within a 5 min period before reaching satiety	volumes will be determined immediately after the 5 min drinking window and compared across study sessions
Secondary	MEP responses	rTMS-induced change in the amplitude of motor evoked potentials (MEP) elicited by paired pulse TMS	before and up to 1 hour after rTMS
Secondary	Heart rate variability	rTMS-induced change in heart rate variability elicited by Valsalva maneuver or diaphragmatic breathing	before and up to 1 hour after rTMS
Secondary	Cardiac Impedance	rTMS-induced change in cardiac impedance variability during Valsalva maneuver or diaphragmatic breathing	before and up to 1 hour after rTMS