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| ID | Type | Description | Link |
|---|---|---|---|
| CIV-19-07-029105 | Other Identifier | Danish Health and Medicines Authority | |
| N-20190020 | Other Identifier | North Denmark Region Committee in Health Research Ethics |
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| Name | Class |
|---|---|
| ElectroCore INC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active treatment | Active Comparator | Non-invasive transcutaneous vagus nerve stimulation applied by the GammaCore device (ElectroCore LLC) |
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| Sham Treatment | Sham Comparator | Inactive sham vagus nerve stimulation applied by the GammaCore sham device (ElectroCore LLC) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non-invasive transcutaneous vagus nerve stimulation | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | At baseline and after 7 days (period 1) of intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Asbjørn M Drewes, Professor | Aalborg University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Steno Diabetes Center North Jutland | Aalborg | 9000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38546822 | Derived | 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. | |
| 33408197 |
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Data can be provided upon request.
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From study end. No end date
Researchers who provide a methodological sound proposal
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| Sham vagus nerve stimulation | 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 |
|
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| 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 |
| 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 | At baseline and after 7 days (period 1) of intervention |
| Sudomotor function | Measured by SUDOSCAN device | At baseline and after 7 days (period 1) of intervention |
| Pan-intestinal imaging | By MR scanning | At baseline and after 7 days (period 1) of intervention |
| Functional brain scan | By MR scanning | 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. | 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. | 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 | 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. | At baseline and after 7 days (period 1) of intervention |
| Glycaemic control | Continuous glucose monitoring (FreeStyle Libre) | 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. | 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 | 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. | 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. | 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. | At baseline in period 1 |
| Derived |
| Okdahl 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. |