Neural Correlates of tVNS

fMRI Clinical Trial

Official title:

Functional Neural Correlates of Transcutaneous Vagal Nerve Stimulation: Effects of Anatomical Site and Waveform Parameters - An Exploratory High Resolution fMRI Study in Healthy Volunteers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04810234
• Other study ID #: 65751.068.2018
• Secondary ID: METC183019
• Status: Recruiting
• Start date: November 1, 2020
• Est. completion date: June 1, 2021

Study information

• Verified date: March 2021
• Source: Maastricht University Medical Center
• Contact: Abraham Beckers, MD
• Phone: +31433881844
• Email: ab.beckers[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Transcutaneous vagal nerve stimulation (tVNS) has been applied to a number of disease areas including visceral pain, depression, cluster headache and Alzheimer's disease. However, there is marked heterogeneity in these studies pertaining to i) the anatomical site of stimulation (neck, inner concha or tragus of ear), and ii) the waveform parameters of the stimulating impulse. This exploratory cross-sectional study will address these knowledge gaps by comparative functional neuroimaging of the neural correlates of tVNS with disparate anatomical sites and electrical waveform characteristics during rest in healthy participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion 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;
• Women on oral contraceptives only
• All subjects should be right-handed.
• Inclusion will be determined on the basis of availability. Subjects should be able to attend for 2 scanning sessions. Exclusion criteria
• Presence of metallic prostheses, pacemakers, metal clips on blood vessels, metal parts in the eye, an intrauterine device, metal braces, 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;
• 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
• Any evidence of structural brain abnormalities examined by anatomical MRI will lead to exclusion

Related Conditions & MeSH terms

• fMRI
• Nucleus of the Solitary Tract (NTS)
• Transcutaneous Vagal Nerve Stimulation (tVNS)

Intervention

Device:
• transcutaneous vagal nerve stimulation (tVNS)
Cervical and auricular transcutaneous stimulation of the vagus nerve

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht
United Kingdom	Queen Mary University of London. Wingate Institute of Neurogastroenterology	London

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Wingate Institute of Neurogastroenterology

Countries where clinical trial is conducted

Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood oxygenation level dependent (BOLD) signal activity in the CAN during tVNS	fMRI related outcome measure	During stimulation (difference between stim on - stim off blocks)
Secondary	Voxel-wise dependent BOLD signal activity in the NTS of the brainstem; somatosensory cortex; insular cortex; ACC, hypothalamus; thalamus and amygdala during auricular tVNS (parameter set 1)	fMRI related outcome measure	During stimulation (difference between stim on - stim off blocks)
Secondary	Voxel-wise dependent BOLD signal activity in the NTS of the brainstem; somatosensory cortex; insular cortex; ACC, hypothalamus; thalamus and amygdala during cervical tVNS )(parameter set 1)	fMRI related outcome measure	During stimulation (difference between stim on - stim off blocks)
Secondary	Voxel-wise dependent BOLD signal activity in the NTS of the brainstem; somatosensory cortex; insular cortex; ACC, hypothalamus; thalamus and amygdala during auricular tVNS (parameter set 2)	fMRI related outcome measure	During stimulation (difference between stim on - stim off blocks)
Secondary	Voxel-wise dependent BOLD signal activity in the NTS of the brainstem; somatosensory cortex; insular cortex; ACC, hypothalamus; thalamus and amygdala during cervical tVNS (parameter set 2)	fMRI related outcome measure	During stimulation (difference between stim on - stim off blocks)
Secondary	Voxel-wise dependent BOLD signal activity in the NTS of the brainstem; somatosensory cortex; insular cortex; ACC, hypothalamus; thalamus and amygdala during subliminal auricular tVNS (parameter set 1)	fMRI related outcome measure	During stimulation (difference between stim on - stim off blocks)
Secondary	Functional connectivity / Network Connectivity of CAN regions during "active tVNS" block [to all 5 points as identified above]	fMRI related outcome measure	During stimulation (difference between stim on - stim off blocks)