Treatment of Complications to Diabetic Autonomic Neuropathy With Vagus Nerve Stimulation

Aalborg University Hospital120 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

120

Conditions

Gastrointestinal Dysfunction Diabetes Mellitus

Interventions

Non-invasive transcutaneous vagus nerve stimulationDEVICE

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

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Steno Diabetes Center North Jutland

Aalborg, Denmark

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: At baseline and after 7 days (period 1) and 8 weeks (period 2) of intervention

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: At baseline and after 7 days (period 1) of intervention

Data from ClinicalTrials.gov

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