Gastrointestinal DysfunctionDAN-VNSNCT04143269
Treatment of Complications to Diabetic Autonomic Neuropathy With Vagus Nerve Stimulation
A study testing Non-invasive transcutaneous vagus nerve stimulation in people with Gastrointestinal Dysfunction and Diabetes Mellitus, run by Aalborg University Hospital at 1 site in Denmark.
Trial summary
The purpose of the DAN-VNS study is to investigate the effects of non-invasive vagal nerve stimulation on gastrointestinal symptoms such as nausea, vomiting, bloating, and diarrhea in people with diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Dysfunction, Diabetes Mellitus
- What is being tested?
- Non-invasive transcutaneous vagus nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Jan 2020to 1 Feb 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Verified diagnosis of diabetes for a minimum of 1 year and with stable medication
- CAN-score ≥ 1 (measured by the Vagus device (Medicus Engineering, Aarhus, Denmark) OR COMPASS-31 score of ≥ 16 OR electrochemical resistance <50µS (hands) and <70µS (feet) assessed with the SUDOSCAN device
- Weighted composite score of Gastroparesis Cardinal Symptom Index (GCSI) and Gastrointestinal Symptom Rating Scale (GSRS) ≥ 2.3
- Ability to read and understand Danish
- Personally signed and dated informed consent documents
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
Who cannot join
- Significant GI diseases not related to diabetes
- Significant cardiovascular diseases
- GI surgery within 3 months prior to study inclusion
- Swallowing disorders
- Blood pressure < 100/60 or > 160/105
- Clinically significant bradycardia or tachycardia
Show all 13Show fewer
- Implanted portable electro-mechanical medical devices including pacemaker, defibrillator, cochlear implant, and infusion pump
- Previous surgery of the vagus nerve
- Active laser treatment for proliferative retinopathy
- Contraindications for MRI
- Any clinical abnormalities, that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results
- Pregnancy or intention to become pregnant or father a child during the course of the study
- Participation in other clinical trials less than three months prior to inclusion, unless such a participation is judged to have no influence on the recordings
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of the DAN-VNS study is to investigate the effects of non-invasive vagal nerve stimulation on gastrointestinal symptoms such as nausea, vomiting, bloating, and diarrhea in people with diabetes.
Read the detailed description
The study is a randomized, double-blinded, sham-controlled, parallel group clinical trial, which will include participants with diabetes and gastrointestinal (GI) problems. These problems may be manifestations of diabetic autonomic neuropathy.
Participants are randomised to received either active non-invasive transcutaneous vagal nerve stimulation (tVNS) or inactive sham stimulation. The study period is divided in two phases. The first phase investigates the effects of short-term, high-intensity tVNS treatment on GI symptoms. The second phase investigates the effects of long-term, middle-intensity tVNS treatment. The primary outcome of both phases is subjective patient evaluation of GI symptoms by the use of validated questionnaires.
A third phase, conducted only on participants, who proved to be responsive to tVNS treatment, will investigate the acute endocrine and metabolic response to short-term tVNS in a randomised cross-over design.
Lastly, healthy volunteers will be included in a cross-sectional, descriptive study in order to provide a comparable baseline dataset.
- Conditions
- Gastrointestinal Dysfunction, Diabetes Mellitus
- Being tested
- Non-invasive transcutaneous vagus nerve stimulation, Sham vagus nerve stimulation
- Keywords
- Vagal nerve stimulation, Gastrointestinal symptoms, Diabetes Mellitus
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-invasive transcutaneous vagus nerve stimulationDevice
Also called GammaCore device
Bilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2). The two periods are separated by a 2 weeks wash-out period.
Sham vagus nerve stimulationDevice
Also called GammaCore sham device
Bilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2). The two periods are separated by a 2 weeks wash-out period.
The sham device produces a slight vibrating sensation, but do not provide any vagal nerve activation
| Study group | Role | What they receive |
|---|---|---|
| Active treatment | Active comparator | Non-invasive transcutaneous vagus nerve stimulation applied by the GammaCore device (ElectroCore LLC) Receives: Device: Non-invasive transcutaneous vagus nerve stimulation |
| Sham Treatment | Sham comparator | Inactive sham vagus nerve stimulation applied by the GammaCore sham device (ElectroCore LLC) Receives: Device: Sham vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective gastrointestinal symptoms
Assessed as changes from baseline in scores from the validated questionnaire Gastroparesis Cardinal Symptom Index (GCSI). The GCSI-score ranges from 0 to 5 with a higher score indicating a higher amount of experienced symptoms
Measured: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
Subjective gastrointestinal symptoms
Assessed as changes from baseline in scores from the validated questionnaire Gastrointestinal Symptom Rating Scale (GSRS). The GSRS-score ranges from 1 to 7 with a higher score indicating a higher amount of experienced symptoms
Measured: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
Secondary outcomes (16)
Holter monitoring
A small patch sensor (ePatch) will be used to monitor the heart rate variability during a period of 5 days. Classical time (RR-interval, SDNN, SDNNi, SDANN, RMSSD) and frequency (VLF, LF, HF and LF/HF) domain heart rate variability parameters will be assessed
Measured: At baseline and after 7 days (period 1) of intervention
Cardiac vagal tone
A three lead electrocardiography device (eMotion Faros) will record the cardiac vagal tone during a period of 5 minutes rest. Cardiac vagal tone is measured on a linear vagal scale with a low score indicating dysfunction of the vagal nerve
Measured: At baseline and after 7 days (period 1) of intervention
Cardiovascular reflex testing
The VAGUS device, will be used to test three different standardised heart reflexes(Ewings battery). From these tests the device calculates a score from 0-3 indicating the degree of autonomic neuropathy, with 0 being no neuropathy and 3 being manifest neuropathy
Measured: At baseline and after 7 days (period 1) of intervention
Sudomotor function
Measured by SUDOSCAN device
Measured: At baseline and after 7 days (period 1) of intervention
Pan-intestinal imaging
By MR scanning
Measured: At baseline and after 7 days (period 1) of intervention
Functional brain scan
By MR scanning
Measured: At baseline and after 7 days (period 1) of intervention
Intestinal transit
Participants will swallow a indigestible wireless motility capsule (SmartPill) in order to assess the transit time of whole gut as well as individual segments.
Measured: At baseline and after 8 weeks (period 2) of intervention
EEG spectral analysis
40 electrodes will be used to record EEG during a period of 5 minutes rest. The results will be used to model connectivity between brain centres as well as the dominating centres of brain. EEG power will be assessed in the Delta, Theta, Alpha, Beta, and Gamma bands between 1 and 70 Hertz. Finally inverse modelling will be conducted to explore the dominating centres of brain activity.
Measured: At baseline and after 7 days (period 1) of intervention
Pain tolerance threshold
Pressure will be applied to the tibial bone and the quadriceps muscle by a handheld pressure algometer. The pain tolerance threshold (measured in kPa) is reached when the participant reports the pain to be intolerable
Measured: At baseline and after 7 days (period 1) of intervention
Cold pressor test
The left hand of the participant is immersed in 2.0 degree (celsius) cold water for up to 2 minutes or until the pain becomes intolerable. The participant is asked to rate the pain on a 10-point Visual Analogue Scale (0 being no pain and 10 being worst imaginable pain) every 10 seconds during the test.
Measured: At baseline and after 7 days (period 1) of intervention
Glycaemic control
Continuous glucose monitoring (FreeStyle Libre)
Measured: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
Level of inflammation
Multiplex analysis of serum samples. Serum concentrations (pg/mL) of inflammatory biomarkers (TNF-alpha, IL-2, IL-4, IL-6 and IL-10) will be assessed.
Measured: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
24-hours blood pressure
Participants wear a device for 24 hours, whivh measures blood pressure (systolic and diastolic) every 15 minutes during daytime and every 30 minutes during the night
Measured: At baseline and 8 weeks (period 2) of intervention
Kidney function
Participants deliver morning urine samples and urine albumine and urin creatinine will be measured.
Measured: At baseline and 7 days (period 1) and 8 weeks (period 2) of intervention
Nerve conduction study - velocities
Nerve conduction test of large fibre function will be performed. Velocities of motor and sensory nerves (peroneal, tibial, ulnar, sural, radial, and median) will be assesed.
Measured: At baseline in period 1
Nerve conduction study - amplitudes
Nerve conduction test of large fibre function will be performed. Amplitudes of motor and sensory nerves (peroneal, tibial, ulnar, sural, radial, and median) will be assesed.
Measured: At baseline in period 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2019
- Study start20 Jan 2020
- Primary completion1 Feb 2023
- Study completion1 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal DysfunctionStudies of the same condition, open and under way.
- More trials run by Aalborg University HospitalThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- ElectroCore INC
- Responsible party
- Principal investigator, Asbjørn Mohr Drewes, Aalborg University Hospital
- Investigators
- Asbjørn M Drewes, Professor, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04143269
- Sponsor's protocol ID
- DAN-VNS
- Other IDs
- CIV-19-07-029105, N-20190020
- Acronym
- DAN-VNS
- Status last verified
- Jun 2023
- First submitted
- 22 Oct 2019
- Last updated
- 7 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Data can be provided upon request.
Publications
Kornum DS, Bertoli D, Kufaishi H, Wegeberg AM, Okdahl T, Mark EB, Hoyer KL, Frokjaer JB, Brock B, Krogh K, Hansen CS, Knop FK, Brock C, Drewes AM. Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial. Diabetologia. 2024 Jun;67(6):1122-1137. doi: 10.1007/s00125-024-06129-0. Epub 2024 Mar 28.
PubMed 38546822Okdahl T, Bertoli D, Brock B, Krogh K, Knop FK, Brock C, Drewes AM. Study protocol for a multicentre, randomised, parallel group, sham-controlled clinical trial investigating the effect of transcutaneous vagal nerve stimulation on gastrointestinal symptoms in people with diabetes complicated with diabetic autonomic neuropathy: the DAN-VNS Study. BMJ Open. 2021 Jan 6;11(1):e038677. doi: 10.1136/bmjopen-2020-038677.
PubMed 33408197
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Complications to Diabetic Autonomic Neuropathy With Vagus Nerve Stimulation
- ClinicalTrials.gov ID
- NCT04143269
- Acronym / sponsor ID
- DAN-VNS / DAN-VNS
- Conditions
- Gastrointestinal Dysfunction, Diabetes Mellitus
- Keywords
- Vagal nerve stimulation, Gastrointestinal symptoms, Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Collaborators
- ElectroCore INC
- Study start
- 20 Jan 2020 (actual)
- Primary completion
- 1 Feb 2023 (actual)
- Study completion
- 1 Feb 2023 (actual)
- First posted
- 29 Oct 2019 (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.
The purpose of the DAN-VNS study is to investigate the effects of non-invasive vagal nerve stimulation on gastrointestinal symptoms such as nausea, vomiting, bloating, and diarrhea in people with diabetes.
Detailed description
The study is a randomized, double-blinded, sham-controlled, parallel group clinical trial, which will include participants with diabetes and gastrointestinal (GI) problems. These problems may be manifestations of diabetic autonomic neuropathy.
Participants are randomised to received either active non-invasive transcutaneous vagal nerve stimulation (tVNS) or inactive sham stimulation. The study period is divided in two phases. The first phase investigates the effects of short-term, high-intensity tVNS treatment on GI symptoms. The second phase investigates the effects of long-term, middle-intensity tVNS treatment. The primary outcome of both phases is subjective patient evaluation of GI symptoms by the use of validated questionnaires.
A third phase, conducted only on participants, who proved to be responsive to tVNS treatment, will investigate the acute endocrine and metabolic response to short-term tVNS in a randomised cross-over design.
Lastly, healthy volunteers will be included in a cross-sectional, descriptive study in order to provide a comparable baseline dataset.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active treatment | Active comparator | Device: Non-invasive transcutaneous vagus nerve stimulationNon-invasive transcutaneous vagus nerve stimulation applied by the GammaCore device (ElectroCore LLC) |
| Sham Treatment | Sham comparator | Device: Sham vagus nerve stimulationInactive sham vagus nerve stimulation applied by the GammaCore sham device (ElectroCore LLC) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years
- Verified diagnosis of diabetes for a minimum of 1 year and with stable medication
- CAN-score ≥ 1 (measured by the Vagus device (Medicus Engineering, Aarhus, Denmark) OR COMPASS-31 score of ≥ 16 OR electrochemical resistance <50µS (hands) and <70µS (feet) assessed with the SUDOSCAN device
- Weighted composite score of Gastroparesis Cardinal Symptom Index (GCSI) and Gastrointestinal Symptom Rating Scale (GSRS) ≥ 2.3
- Ability to read and understand Danish
Key exclusion criteria (13 listed)
- Significant GI diseases not related to diabetes
- Significant cardiovascular diseases
- GI surgery within 3 months prior to study inclusion
- Swallowing disorders
- Blood pressure < 100/60 or > 160/105
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 |
|---|---|---|
| Non-invasive transcutaneous vagus nerve stimulationAlso: GammaCore deviceBilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2). The two periods are separated by a 2 weeks wash-out period. | Device | Active treatment |
| Sham vagus nerve stimulationAlso: GammaCore sham deviceBilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2). The two periods are separated by a 2 weeks wash-out period. The sham device produces a slight vibrating sensation, but do not provide any vagal nerve activation | Device | Sham Treatment |
Primary outcome
Subjective gastrointestinal symptoms
Time frame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
Assessed as changes from baseline in scores from the validated questionnaire Gastroparesis Cardinal Symptom Index (GCSI). The GCSI-score ranges from 0 to 5 with a higher score indicating a higher amount of experienced symptoms
Subjective gastrointestinal symptoms
Time frame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
Assessed as changes from baseline in scores from the validated questionnaire Gastrointestinal Symptom Rating Scale (GSRS). The GSRS-score ranges from 1 to 7 with a higher score indicating a higher amount of experienced symptoms
16 secondary outcomes
Holter monitoring
Time frame: At baseline and after 7 days (period 1) of intervention
Cardiac vagal tone
Time frame: At baseline and after 7 days (period 1) of intervention
Cardiovascular reflex testing
Time frame: At baseline and after 7 days (period 1) of intervention
Sudomotor function
Time frame: At baseline and after 7 days (period 1) of intervention
Pan-intestinal imaging
Time frame: At baseline and after 7 days (period 1) of intervention
Functional brain scan
Time frame: At baseline and after 7 days (period 1) of intervention
Intestinal transit
Time frame: At baseline and after 8 weeks (period 2) of intervention
EEG spectral analysis
Time frame: At baseline and after 7 days (period 1) of intervention
Pain tolerance threshold
Time frame: At baseline and after 7 days (period 1) of intervention
Cold pressor test
Time frame: At baseline and after 7 days (period 1) of intervention
Glycaemic control
Time frame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
Level of inflammation
Time frame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
24-hours blood pressure
Time frame: At baseline and 8 weeks (period 2) of intervention
Kidney function
Time frame: At baseline and 7 days (period 1) and 8 weeks (period 2) of intervention
Nerve conduction study - velocities
Time frame: At baseline in period 1
Nerve conduction study - amplitudes
Time frame: At baseline in period 1
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 7 Jun 2023.
- Derived from this study: PubMed 38546822Kornum DS, Bertoli D, Kufaishi H, Wegeberg AM, Okdahl T, Mark EB, Hoyer KL, Frokjaer JB, Brock B, Krogh K, Hansen CS, Knop FK, Brock C, Drewes AM. Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial. Diabetologia. 2024 Jun;67(6):1122-1137. doi: 10.1007/s00125-024-06129-0. Epub 2024 Mar 28.
- Derived from this study: PubMed 33408197Okdahl T, Bertoli D, Brock B, Krogh K, Knop FK, Brock C, Drewes AM. Study protocol for a multicentre, randomised, parallel group, sham-controlled clinical trial investigating the effect of transcutaneous vagal nerve stimulation on gastrointestinal symptoms in people with diabetes complicated with diabetic autonomic neuropathy: the DAN-VNS Study. BMJ Open. 2021 Jan 6;11(1):e038677. doi: 10.1136/bmjopen-2020-038677.
- Individual participant dataSharing planned: Yes. Data can be provided upon request.
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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.
Asbjørn M Drewes, Professor principal investigator
Aalborg University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Non-invasive transcutaneous vagus nerve stimulation in people with Gastrointestinal Dysfunction and Diabetes Mellitus, run by Aalborg University Hospital at 1 site in Denmark.
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 13 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 7 Jun 2023. 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 Denmark. 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?
Subjective gastrointestinal symptoms (time frame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04143269, which also lists 2 linked publications.
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 7 Jun 2023.