Healthy Adult Participants
Conditions
Keywords
Vagal Nerve Stimulation, Upper GI motility, Randomised Controlled Trial, Antroduodenal Manometry, Gastric Alimetry
Brief summary
This single-center randomized controlled cross-over trial aims to investigate the effect of transcutaneous auricular vagus nerve stimulation on upper gastrointestinal motility in healthy individuals. The primary aim of this study is to assess the impact of tVNS on gut motor function, with regards to its potential to induce phase III contractions in the upper GI tract. Secondary objectives include: * To study the effect of tVNS on other parameters characterizing upper GI motility such as the number of duodenal phase III contractions, gastric and duodenal phase MMCs, amplitude of antral contractions and motility index * To study the effect of tVNS on plasma levels of motilin and PP * To evaluate the effect of tVNS on parameters related to autonomic outflow, using a Shimmer3 GSR Sensor for heart rate variability and skin conductance. * To compare the results of the measurements of antroduodenal manometry with measurements of Gastric Alimetry Participants will undergo tVNS (applied to the cymba conchae of the left ear) alternating with sham stimulation (using a non-conducting electrode) in a blinded, pre-randomized fashion, using two 4-hour blocks during an 8-hour fasted antroduodenal manometry recording period. Optionally, participants may simultaneously also undergo body surface gastric mapping using the Gastric Alimetry system.
Detailed description
Visit 1 (screening visit) Following written informed consent, the medical history of each subject will be checked during a structured interview. A pregnancy will be excluded by a urine test (due to the use or fluoroscopy during insertion of the manometry catheter) and a 12-lead ECG will be performed at the end of the screening visit. The rationale for this is to ensure no evidence of cardiac conduction disorders and an additional safety step to ensure no cardiac dysrhythmic affect with tVNS use. All information obtained during the screening visit will be recorded in using an electronic CRF provided by Castor EDC, provided by the Clinical Trial Centre Maastricht (CTCM). Visit 2 (test day) Participants will arrive after an overnight fast at the GI physiology unit of the Maastricht University Medical Center, where a trained and experienced nurse will insert an antroduodenal manometry catheter through the nose into the duodenum under fluoroscopy control and supervision of a gastroenterologist (as per routine clinical procedure). Using this catheter, stomach and duodenum motility patterns will be recorded for 8 hours. After the manometry is inserted, the tVNS device will be connected with an electrode which delivers stimulation transcutaneous in the outer ear. Participants will receive two types of stimulation (i.e. tVNS vs sham) in 2 blocks of 4 hours during the 8-hour registration period. The order of stimulation applied is randomized. Gastric phase III contractions generally occur every 90 minutes, so the 4-hour period is considered sufficient to detect two phase III contractions considered sufficient to detect the two phase III contractions.(10) An iv catheter will be inserted to draw blood during the 8-hour registration period. Blood samples, each witch a maximum volume of 10 mL, will be taken every 30 minutes to measure motilin and PP as surrogate markers of vagal efferent influence on GI motor function. In addition, autonomic parameters will be registered during the entire test period, using a Shimmer3 GSR sensor. After the 8-hour test period, the manometry catheter, the electrodes of the tVNS device and the iv cannula are removed. Additionally, participants may opt to take part in a body surface gastric mapping assessment. This non-invasive, electrophysiological measurement is performed using the Gastric Alimetry system, which involves placing a large adhesive patch with multiple electrodes on the upper abdomen. The system records gastric myoelectrical activity over time, providing insight into gastric motility patterns. The measurement is conducted concurrently with the manometry registration period.
Interventions
DEVICEVagal Nerve Stimulation
taVNS will be provided during a 4-hour block of the 8-hour fasted antroduodenal manometry recording period.
DEVICESham stimulation
Sham stimulation will be provided during a 4-hour block of the 8-hour fasted antroduodenal manometry recording period.
Sponsors
Daniel Keszthelyi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants (defined as those without a pre-existing medical comorbidity, including those without a history of cardiac arrhythmia). * Age between 18 and 55 years. * Ability to understand and speak the Dutch language.
Exclusion criteria
* Pregnancy or lactation. * Use of any substances (such as medication or recreational drugs) influencing gastrointestinal motility * Not meeting the inclusion criteria above. * Students and employees of Maastricht University are not precluded from participation, unless they have a direct personal, professional of hierarchical position with regards to any of the study team members or their department.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A clinically meaningful increase in phase III contractions | Assessed during one single test day, from pre-intervention baseline to post-stimulation (approximately 8-9 hours) | A clinically meaningful increase in the number of phase III contractions of antral origin in the fasted period during the tVNS stimulation compared to the sham stimulation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A clinically relevant increase in other upper GI motility parameters | Assessed during one single test day, from pre-intervention baseline to post-stimulation (approximately 8-9 hours) | A clinically relevant increase in other parameters characterizing upper GI motility such as the number of duodenal phase III contractions, gastric and duodenal phase MMCs, amplitude of antral contractions and motility index |
| Concentration of plasma motilin and pancreatic polypeptide | Assessed during one single test day, from pre-intervention baseline to post-stimulation (approximately 8-9 hours) | Changes in plasma motilin and pancreatic polypeptide following taVNS vs. sham stimulation |
| Autonomic response: heart rate variability | Assessed during one single test day, from pre-intervention baseline to post-stimulation (approximately 8-9 hours) | Changes in heart rate variability measured continuously using a Shimmer3 GSR sensor |
| Electrodermal response: skin conductance | Assessed during one single test day, from pre-intervention baseline to post-stimulation (approximately 8-9 hours) | Changes in skin conductance following taVNS vs sham stimulation, assessed continuously using a Shimmer3 GSR sensor. |
| Agreement between gastric motility measurements obtained by antroduodenal manometry and Gastric Alimetry | Assessed during one single test day, from pre-intervention baseline to post-stimulation (approximately 8-9 hours) | Agreement between antroduodenal manometry and Gastric Alimetry measurements obtained simultaneously. |
Countries
Netherlands
Contacts
CONTACTKimberly Hawinkels, MD
PRINCIPAL_INVESTIGATORDaniel Keszthelyi, MD, PhD
Maastricht University Medical Center
Outcome results
None listed