Vagus Nerve Stimulation in Crohn's Disease
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Study of the Safety and Efficacy of Neurostimulation of the Cholinergic Anti-Inflammatory Pathway Using a Vagal Nerve Stimulation Device in Patients With Active Refractory Crohn's Disease|
- Crohn's Disease Activity Index [ Time Frame: Week 16 ]
- Simple Endoscopic Score for Crohn's Disease (SES-CD) [ Time Frame: Week 16 ]
- Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Week 16 ]
- Heart Rate Variability (HRV) [ Time Frame: Week 16 ]
- Changes in Whole Blood Lipopolysaccharide-Induced TNF Release Assay [ Time Frame: Week 16 ]
- Serum Inflammation Mediators using Meso Scale Discovery Inflammation Multiplex Assay [ Time Frame: Week 16 ]Change in level of each mediator from baseline to Week 16
- Adverse Events [ Time Frame: Week 16 ]
- Device Deficiencies meeting the event definition from EN ISO 14155:2011 [ Time Frame: Week 16 ]Number of events occurring between first use of the device and Week 16 Visit
|Study Start Date:||December 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Experimental: vagus nerve stimulation
Patients will have an implanted vagus nerve stimulation device.
Device: Vagus Nerve Stimulation Device
Cyberonics VNS System
This will be an open-label, multicenter study of the safety, biological activity and clinical outcomes of an active implantable VNS device in patients with active refractory CD.
Patients will sign informed consent prior to screening and will undergo all screening and baseline assessment procedures including endoscopy and endoscopic biopsy prior to planned VNS implantation date. Those who meet all of the inclusion criteria and none of the exclusion criteria will be considered enrolled and will be implanted.
After a minimum of 14 days following the implantation, patients will have their first in-clinic visit (Week 0 Visit), during which they will begin self-delivered once-daily stimulation using the VNS device.
Patients will return for weekly visits between Weeks 1-4, at which time outcomes and safety assessments will be taken. At each visit between weeks 1 and 4, an attempt will be made to increase the output current to the maximum level tolerated. At the Week 4 Visit, another attempt to increase the output current will be made and the daily stimulation time will in addition be incremented by 60 seconds to 2 minutes total.
At the Week 6 Visit safety and outcomes assessments will be taken and another attempt to increase the output current will be made, and the daily stimulation time will in addition be incremented to 5 minutes total.
Patients will return at Week 8, at which time safety and outcomes assessments will be taken. If the patient has not achieved a clinical remission by CDAI, the frequency of stimulations will increase from once daily to 4 times daily.
At Week 12, the patient will return for safety and outcomes assessments. The final study visit will be at the Week 16 Visit, at which time patients will have final primary endpoint safety and outcomes assessments, including a follow-up endoscopy with endoscopic biopsy. If patients terminate the study prior to week 16, every effort will be made to perform all Week 16 Visit procedures during an Early Termination Visit.
Patients who complete the study will have the option to enroll in a long-term extension study. If they do not wish to participate in the extension study they can opt to either have their device permanently inactivated and left in place or have the device surgically explanted.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02311660
|Clinical Hospital Dubrava|
|Humanitas Research Hospital|
|Academic Medical Center|
|Karolinska University Hospital, Solna|
|Principal Investigator:||Geert D'Haens, M.D., Ph.D.||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|