Healthy FemalesNCT06659172
Effects of tVNS on Visceral Pain
A study testing taVNS in people with Healthy Females and Vagus Nerve Stimulation, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Transcutaneous auricular vagal nerve stimulation (taVNS) has shown promise in reducing chronic abdominal pain, such as in irritable bowel syndrome (IBS). This pain is thought to result from a disruption in gut-brain communication involving the vagus nerve. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Females, Vagus Nerve Stimulation, Abdominal Pain
- What is being tested?
- taVNS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 17 Apr 2023to 3 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Of female sex;
- Healthy participants (defined as those without a pre-existing medical comorbidity)
- Age between 18 and 40 years;
- BMI between 18 and 30 kg/m2;
- All subjects should use some form of contraception (for IUDs only Mirena is accepted)
- All subjects should be right-handed.
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Presence of metallic prostheses, pacemakers, metal clips on blood vessels, metal parts in the eye, an intrauterine device (with the exception of the Mirena IUD), metal braces, facial tattoos and/or other metal objects;
- History of major head trauma or head/brain surgery;
- History of claustrophobia;
- History of severe or chronic cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, haematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol;
- Use of regular medication, including vitamin and iron supplementation, except oral contraceptives, within 14 days prior to start of the study;
Show all 21Show fewer
- Pregnancy, lactation, wish to become pregnant;
- High alcohol consumption (>15 alcoholic units consumed per week);
- Using drugs of abuse;
- Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study;
- Participants unable to provide informed consent
- Participants with any systemic disease or medications that may influence the autonomic nervous system (e.g. beta-agonists or Parkinson's disease)
- Current smokers or current use of nicotine in any other way (including E-cigarettes and patches)
- History of clinical anxiety or depression, or a hospital anxiety or depression score >8
- Participants whom score 8 or more on the HADS-questionnaire at study commencement
- Patient whom have cardiovascular conduction problems
- Patient with cochlear implants
- Not meeting any of the inclusion criteria above
- No given permission to register participation in electronic patient file at MUMC+ and to add records of transnasal gastroduodenoscopy
- No given permission to inform incidental findings to the general practitioner
- Any evidence of structural brain abnormalities examined by anatomical MRI will lead to exclusion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Transcutaneous Vagal Nerve Stimulation on the Processing of Visceral Pain Signals: a High Resolution fMRI Study in Healthy Volunteers
Transcutaneous auricular vagal nerve stimulation (taVNS) has shown promise in reducing chronic abdominal pain, such as in irritable bowel syndrome (IBS). This pain is thought to result from a disruption in gut-brain communication involving the vagus nerve. Using brain imaging, we developed a pain model involving capsaicin (the spicy component in red peppers) to study this interaction. This study aims to explore how taVNS affects this pain model in healthy volunteers.
Read the detailed description
Abdominal pain is often caused by conditions like irritable bowel syndrome (IBS) and functional dyspepsia (FD), which are chronic and can fluctuate daily. IBS and FD affect about 6% and 10% of the general population, respectively. Many patients visiting gastroenterology clinics suffer from these conditions, and pain is the most challenging symptom to manage. Conventional treatments often don't provide lasting relief, affecting patients' quality of life and causing significant socio-economic impact.
The underlying causes of IBS and FD are not well understood, making it difficult to develop effective treatments. These conditions are considered disorders of the gut-brain interaction, involving communication between the gut and brain via the vagus nerve. The vagus nerve sends sensory information from the gut to the brainstem, particularly the nucleus tractus solitarius (NTS), which then communicates with other brain areas involved in pain perception.
The vagus nerve has a branch that innervates the external ear, making it accessible for non-invasive stimulation. Transcutaneous auricular vagal nerve stimulation (taVNS) has been used experimentally for conditions like migraines and fibromyalgia. A recent trial showed that daily taVNS can reduce abdominal pain in adolescents with functional abdominal pain and IBS. Additionally, studies using advanced brain imaging have shown that taVNS activates the NTS. However, it's unclear if this activation is responsible for the pain-relieving effects of taVNS.
New neuroimaging techniques allow for detailed studies of gut-brain communication and the effects of taVNS. Understanding these mechanisms could help develop taVNS as a safe and effective treatment for abdominal pain.
Preliminary Results:
We developed a human pain model using capsaicin (a component of chili peppers) infused into the duodenum to simulate abdominal pain. This model reliably triggers pain and activates brain regions involved in pain perception, including the NTS. This model is useful for studying treatments like taVNS for visceral pain relief.
Clinical Significance:
taVNS is gaining attention as a treatment for various conditions, but its effects are not yet fully understood. This study aims to explore the neurobiological effects of taVNS on visceral pain using advanced imaging techniques. Establishing these effects is crucial for integrating taVNS into clinical practice.
Vagus Nerve Stimulation (VNS):
VNS was first used in 1988 to treat epilepsy with surgically implanted devices. Recently, non-invasive taVNS methods have been developed, targeting the auricular branch of the vagus nerve in the ear. taVNS is safe, well-tolerated, and user-friendly.
Advanced Imaging:
Using 7 Tesla MRI provides higher resolution imaging than standard 1.5 or 3 Tesla scanners, allowing for detailed brain studies. These scanners are becoming more common and are safe for research. In the Netherlands, several institutions use 7 Tesla scanners for patient research without reported adverse effects.
- Conditions
- Healthy Females, Vagus Nerve Stimulation, Abdominal Pain
- Being tested
- taVNS
- Medical subject headings
- Abdominal Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
taVNSDevice
transauricular vagus nerve stimulation
| Study group | Role | What they receive |
|---|---|---|
| taVNS | Active comparator | The vagus nerve will be stimulated electrically by using an MRI-safe electrode. The concha of the right ear will be stimulated. Receives: Device: taVNS |
| Sham stimulation | Placebo comparator | The vagus nerve will be stimulated electrically by using an MRI-safe electrode. The earlobe of the right ear will be stimulated. Receives: Device: taVNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood oxygenation level dependent BOLD signal activity in the NTS
Main Outcome Measure
The main outcome measure is the difference in Blood Oxygen Level Dependent (BOLD) response between taVNS and sham stimulation. The BOLD response is detected using fMRI, which relies on the different magnetic properties of oxygenated and deoxygenated hemoglobin. When neural tissue is more active, it receives increased blood flow, resulting in a higher percentage of oxygenated hemoglobin and a detectable change in the MRI signal. This change, known as the BOLD response, allows us to identify areas of greater neural activity. The BOLD response is a reliable indicator of brain activation.
Measured: During fMRI
Secondary outcomes (4)
fMRI results
BOLD signal activity in the Cingulate Cortex, Insula, Thalamus, Prefrontal Cortex, Primary, Secondary Somatosensory Cortex, Amygdala, Periaqueductal Grey, and Brainstem
Measured: During fMRI
fMRI results
Baseline Cerebral Blood Flow
Measured: During fMRI
fMRI results
Temporal BOLD signal activity (i.e. change over time) in all brain and the above defined regions.
Measured: During fMRI
Subjective pain scores
VAS scores
Measured: During fMRI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2024
- Study start17 Apr 2023
- Primary completion3 Jan 2025
- Study completion3 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy FemalesStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The study design is a randomized controlled fMRI study. Subjects will receive two types of stimulation (i.e. taVNS vs sham) during a single scanning visit. The order of stimulation applied during each visit is randomised. Infusion of capsaicin via a nasoduodenal tube will be used as co-intervention.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- D. Keszthelyi, Principal investigator, Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06659172
- Sponsor's protocol ID
- NL77976.068.21
- Status last verified
- Feb 2025
- First submitted
- 1 Aug 2024
- Last updated
- 17 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Transcutaneous Vagal Nerve Stimulation on the Processing of Visceral Pain Signals: a High Resolution fMRI Study in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT06659172
- Acronym / sponsor ID
- NL77976.068.21
- Conditions
- Healthy Females, Vagus Nerve Stimulation, Abdominal Pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 17 Apr 2023 (actual)
- Primary completion
- 3 Jan 2025 (actual)
- Study completion
- 3 Jan 2025 (actual)
- First posted
- 26 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Transcutaneous auricular vagal nerve stimulation (taVNS) has shown promise in reducing chronic abdominal pain, such as in irritable bowel syndrome (IBS). This pain is thought to result from a disruption in gut-brain communication involving the vagus nerve. Using brain imaging, we developed a pain model involving capsaicin (the spicy component in red peppers) to study this interaction. This study aims to explore how taVNS affects this pain model in healthy volunteers.
Detailed description
Abdominal pain is often caused by conditions like irritable bowel syndrome (IBS) and functional dyspepsia (FD), which are chronic and can fluctuate daily. IBS and FD affect about 6% and 10% of the general population, respectively. Many patients visiting gastroenterology clinics suffer from these conditions, and pain is the most challenging symptom to manage. Conventional treatments often don't provide lasting relief, affecting patients' quality of life and causing significant socio-economic impact.
The underlying causes of IBS and FD are not well understood, making it difficult to develop effective treatments. These conditions are considered disorders of the gut-brain interaction, involving communication between the gut and brain via the vagus nerve. The vagus nerve sends sensory information from the gut to the brainstem, particularly the nucleus tractus solitarius (NTS), which then communicates with other brain areas involved in pain perception.
The vagus nerve has a branch that innervates the external ear, making it accessible for non-invasive stimulation. Transcutaneous auricular vagal nerve stimulation (taVNS) has been used experimentally for conditions like migraines and fibromyalgia. A recent trial showed that daily taVNS can reduce abdominal pain in adolescents with functional abdominal pain and IBS. Additionally, studies using advanced brain imaging have shown that taVNS activates the NTS. However, it's unclear if this activation is responsible for the pain-relieving effects of taVNS.
New neuroimaging techniques allow for detailed studies of gut-brain communication and the effects of taVNS. Understanding these mechanisms could help develop taVNS as a safe and effective treatment for abdominal pain.
Preliminary Results:
We developed a human pain model using capsaicin (a component of chili peppers) infused into the duodenum to simulate abdominal pain. This model reliably triggers pain and activates brain regions involved in pain perception, including the NTS. This model is useful for studying treatments like taVNS for visceral pain relief.
Clinical Significance:
taVNS is gaining attention as a treatment for various conditions, but its effects are not yet fully understood. This study aims to explore the neurobiological effects of taVNS on visceral pain using advanced imaging techniques. Establishing these effects is crucial for integrating taVNS into clinical practice.
Vagus Nerve Stimulation (VNS):
VNS was first used in 1988 to treat epilepsy with surgically implanted devices. Recently, non-invasive taVNS methods have been developed, targeting the auricular branch of the vagus nerve in the ear. taVNS is safe, well-tolerated, and user-friendly.
Advanced Imaging:
Using 7 Tesla MRI provides higher resolution imaging than standard 1.5 or 3 Tesla scanners, allowing for detailed brain studies. These scanners are becoming more common and are safe for research. In the Netherlands, several institutions use 7 Tesla scanners for patient research without reported adverse effects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- The study design is a randomized controlled fMRI study. Subjects will receive two types of stimulation (i.e. taVNS vs sham) during a single scanning visit. The order of stimulation applied during each visit is randomised. Infusion of capsaicin via a nasoduodenal tube will be used as co-intervention.
| Arm | Type | Receives |
|---|---|---|
| taVNS | Active comparator | Device: taVNSThe vagus nerve will be stimulated electrically by using an MRI-safe electrode. The concha of the right ear will be stimulated. |
| Sham stimulation | Placebo comparator | Device: taVNSThe vagus nerve will be stimulated electrically by using an MRI-safe electrode. The earlobe of the right ear will be stimulated. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Of female sex;
- Healthy participants (defined as those without a pre-existing medical comorbidity)
- Age between 18 and 40 years;
- BMI between 18 and 30 kg/m2;
Key exclusion criteria (21 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Presence of metallic prostheses, pacemakers, metal clips on blood vessels, metal parts in the eye, an intrauterine device (with the exception of the Mirena IUD), metal braces, facial tattoos and/or other metal objects;
- History of major head trauma or head/brain surgery;
- History of claustrophobia;
- History of severe or chronic cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, haematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| taVNStransauricular vagus nerve stimulation | Device | Sham stimulation, taVNS |
Primary outcome
Blood oxygenation level dependent BOLD signal activity in the NTS
Time frame: During fMRI
Main Outcome Measure The main outcome measure is the difference in Blood Oxygen Level Dependent (BOLD) response between taVNS and sham stimulation. The BOLD response is detected using fMRI, which relies on the different magnetic properties of oxygenated and deoxygenated hemoglobin. When neural tissue is more active, it receives increased blood flow, resulting in a higher percentage of oxygenated hemoglobin and a detectable change in the MRI signal. This change, known as the BOLD response, allows us to identify areas of greater neural activity. The BOLD response is a reliable indicator of brain activation.
4 secondary outcomes
fMRI results
Time frame: During fMRI
fMRI results
Time frame: During fMRI
fMRI results
Time frame: During fMRI
Subjective pain scores
Time frame: During fMRI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
D. Keszthelyi principal investigator
Maastricht University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing taVNS in people with Healthy Females and Vagus Nerve Stimulation, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood oxygenation level dependent BOLD signal activity in the NTS (time frame: During fMRI). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2025.