Treatment of Complications to Diabetic Autonomic Neuropathy With Vagus Nerve Stimulation

NCT ID: NCT04143269

Last Updated: 2023-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-20
• Study Completion Date: 2023-02-01

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.

Conditions

Gastrointestinal Dysfunction; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active treatment

Non-invasive transcutaneous vagus nerve stimulation applied by the GammaCore device (ElectroCore LLC)

Group Type: ACTIVE_COMPARATOR

Non-invasive transcutaneous vagus nerve stimulation

Intervention Type: 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 Treatment

Inactive sham vagus nerve stimulation applied by the GammaCore sham device (ElectroCore LLC)

Group Type: SHAM_COMPARATOR

Sham vagus nerve stimulation

Intervention Type: 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

Interventions

Non-invasive transcutaneous vagus nerve stimulation

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.

Intervention Type: DEVICE

Sham vagus nerve stimulation

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

Intervention Type: DEVICE

Other Intervention Names

GammaCore device; GammaCore sham device

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ElectroCore INC

INDUSTRY

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Asbjørn Mohr Drewes

Professir, Chief Physician, MD, PhD, DMSc

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Asbjørn M Drewes, Professor

Role: PRINCIPAL_INVESTIGATOR

Aalborg University Hospital

Locations

Steno Diabetes Center North Jutland

Aalborg, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 38546822 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33408197 (View on PubMed)

Other Identifiers

CIV-19-07-029105

Identifier Type: OTHER

Identifier Source: secondary_id

N-20190020

Identifier Type: OTHER

Identifier Source: secondary_id

DAN-VNS

Identifier Type: -

Identifier Source: org_study_id