Clinical trial NCT04143269: Treatment of Complications to Diabetic Autonomic Neuropathy With Vagus Nerve Stimulation
Official title: Treatment of Complications to Diabetic Autonomic Neuropathy With Vagus Nerve Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastrointestinal Dysfunction
Diabetes Mellitus
Keywords: Vagal nerve stimulation
Gastrointestinal symptoms
Diabetes Mellitus
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: ElectroCore INC
First posted: 2019-10-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Subjective gastrointestinal symptoms
timeFrame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
measure: Subjective gastrointestinal symptoms
timeFrame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
Secondary outcomes:
measure: Holter monitoring
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Cardiac vagal tone
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Cardiovascular reflex testing
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Sudomotor function
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Pan-intestinal imaging
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Functional brain scan
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Intestinal transit
timeFrame: At baseline and after 8 weeks (period 2) of intervention
measure: EEG spectral analysis
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Pain tolerance threshold
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Cold pressor test
timeFrame: At baseline and after 7 days (period 1) of intervention
measure: Glycaemic control
timeFrame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
measure: Level of inflammation
timeFrame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention
measure: 24-hours blood pressure
timeFrame: At baseline and 8 weeks (period 2) of intervention
measure: Kidney function
timeFrame: At baseline and 7 days (period 1) and 8 weeks (period 2) of intervention
measure: Nerve conduction study - velocities
timeFrame: At baseline in period 1
measure: Nerve conduction study - amplitudes
timeFrame: At baseline in period 1
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Steno Diabetes Center North Jutland
Study officials:
affiliation: Aalborg University Hospital
name: Asbjørn M Drewes, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.