Crohn's DiseaseNCT02311660
Vagus Nerve Stimulation in Crohn's Disease
A study testing Vagus Nerve Stimulation Device in people with Crohn's Disease, run by SetPoint Medical Corporation at 4 sites in 4 countries.
Trial summary
This is an open label interventional study using an implantable vagus nerve stimulation device in patients with Crohn's disease who have active disease despite treatment with a tumor necrosis factor (TNF) antagonist drug. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Vagus Nerve Stimulation Device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Dec 2014to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects aged 18-75 years, inclusive
- Written informed consent prior to any of the screening procedures
- Diagnosis of Crohn's disease for more than 4 months prior to Week -4 Visit, with small bowel and/or colonic involvement
- Current evidence of moderately-to-severely active disease defined by a Week -4 Visit Crohn's Disease Activity Index (CDAI) score of 220 to 450, inclusive
- Simple Endoscopic Score for Crohn's Disease evaluation at baseline showing presence of a minimal ulcer score of 2 or 3 in at least 1 segment
- Levels of fecal calprotectin greater than or equal to 200 microgram/gram feces at Week -4 Visit
- History of inadequate response and/or intolerance or adverse events leading to discontinuation of one or more TNF-alpha inhibitors (e.g., infliximab, adalimumab, or certolizumab pegol), or vedolizumab
- Female subjects of child-bearing potential are eligible if not pregnant, not planning to become pregnant during the course of the study, and committed to use of contraceptive methods with a failure rate of less than 1 percent per year
Who cannot join
- Celiac disease
- Diagnosis of ulcerative or indeterminate colitis
- Enterocutaneous, abdominal or pelvic fistulae with abscesses, or fistulae likely to require surgery during the course of the study period
- Bowel surgery, other than appendectomy, within 12 weeks prior to Week -4 Visit and/or has planned surgery or deemed likely to need surgery for Crohn's disease during the study period
- Extensive colonic resection, subtotal or total colectomy
- Presence of ileostomies, colostomies or rectal pouches
Show all 35Show fewer
- Fixed symptomatic stenoses of small bowel or colon
- History of more than 3 small bowel resections or diagnosis of short bowel syndrome
- Use of prohibited medications inside the specified washout period (prior to Week -4 Visit), and throughout the study. Prohibited medications include the following:
- TNF antagonists and vedolizumab may continue throughout the study, but treatments should have been given at a stable dose for at least 6 months prior to the screening date and should be maintained at this level throughout the study
- Use of any natalizumab within 8 weeks
- Use of glucocorticoids at doses greater than 10 mg prednisone orally QD, or an equivalent dose of other oral or parenteral glucocorticoids within 4 weeks
- Use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 4 weeks
- Use of intravenous antibiotics for Crohn's disease within 4 weeks
- Use of tube or enteral feeding, or elemental diet within 2 weeks
- Rectal Treatment: Use of 5-aminosalicylates or corticosteroid enemas or suppositories within 2 weeks
- Azathioprine, 6-mercaptopurine and methotrexate can be continued throughout the trial. These medications must have been used for >12 weeks, at stable dose for at least 3 weeks prior to the Week -4 Visit.
- Leukocytopheresis or granulocytopheresis within 2 weeks prior to Week -4 Visit
- Positive immunoassay for Clostridium difficile at Week -4 Visit
- Known HIV infection
- Known active in infection with Hepatitis B Virus or Hepatitis C Virus
- Current evidence of, or has been treated for a malignancy within the past five years (other than localized basal cell or squamous cell skin cancer, cervical dysplasia, or any cancer which has been fully staged as in situ and has been fully resected)
- History of evidence of adenomatous colonic polyps that have not been removed.
- Use of any investigational product within 30 days prior to Week -4 Visit for small molecules, or 8 weeks prior for monoclonal antibodies
- Significant psychiatric disease or substance abuse
- History of unilateral or bilateral vagotomy
- History of recurrent vaso-vagal syncope episodes
- Known obstructive sleep apnea
- Known history of cardiac rhythm disturbances, atrio-ventricular block of greater than first degree, or cardiac conduction pathway abnormalities other than isolated right bundle branch block or isolated left anterior fascicle block
- Significant pharyngeal dysfunction or swallowing difficulties
- Pre-existing clinically significant vocal cord damage or hoarseness
- Previously implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators)
- Asthma or chronic obstructive pulmonary disease not controlled by medications, or any other disease causing clinically significant dyspnea at time of screening
- A greater than or equal to 40 pack-year smoking history
- Active peptic ulcer disease
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
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
This is an open label interventional study using an implantable vagus nerve stimulation device in patients with Crohn's disease who have active disease despite treatment with a tumor necrosis factor (TNF) antagonist drug.
Read the detailed description
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.
- Conditions
- Crohn's Disease
- Being tested
- Vagus Nerve Stimulation Device
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagus Nerve Stimulation DeviceDevice
Cyberonics VNS System
| Study group | Role | What they receive |
|---|---|---|
| vagus nerve stimulation | Experimental | Patients will have an implanted vagus nerve stimulation device. Receives: Device: Vagus Nerve Stimulation Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Crohn's Disease Activity Index
Measured: Week 16
Secondary outcomes (7)
Simple Endoscopic Score for Crohn's Disease (SES-CD)
Measured: Week 16
Inflammatory Bowel Disease Questionnaire (IBDQ)
Measured: Week 16
Heart Rate Variability (HRV)
Measured: Week 16
Changes in Whole Blood Lipopolysaccharide-Induced TNF Release Assay
Measured: Week 16
Serum Inflammation Mediators using Meso Scale Discovery Inflammation Multiplex Assay
Change in level of each mediator from baseline to Week 16
Measured: Week 16
Adverse Events
Measured: Week 16
Device Deficiencies meeting the event definition from EN ISO 14155:2011
Number of events occurring between first use of the device and Week 16 Visit
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionAug 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SetPoint Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Geert D'Haens, M.D., Ph.D., Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02311660
- Sponsor's protocol ID
- SPM-007
- Status last verified
- Aug 2017
- First submitted
- 3 Dec 2014
- Last updated
- 3 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02311660
- Acronym / sponsor ID
- SPM-007
- Conditions
- Crohn's Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- SetPoint Medical CorporationIndustry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 8 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label interventional study using an implantable vagus nerve stimulation device in patients with Crohn's disease who have active disease despite treatment with a tumor necrosis factor (TNF) antagonist drug.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vagus nerve stimulation | Experimental | Device: Vagus Nerve Stimulation DevicePatients will have an implanted vagus nerve stimulation device. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female subjects aged 18-75 years, inclusive
- Written informed consent prior to any of the screening procedures
- Diagnosis of Crohn's disease for more than 4 months prior to Week -4 Visit, with small bowel and/or colonic involvement
- Current evidence of moderately-to-severely active disease defined by a Week -4 Visit Crohn's Disease Activity Index (CDAI) score of 220 to 450, inclusive
- Simple Endoscopic Score for Crohn's Disease evaluation at baseline showing presence of a minimal ulcer score of 2 or 3 in at least 1 segment
Key exclusion criteria (35 listed)
- Celiac disease
- Diagnosis of ulcerative or indeterminate colitis
- Enterocutaneous, abdominal or pelvic fistulae with abscesses, or fistulae likely to require surgery during the course of the study period
- Bowel surgery, other than appendectomy, within 12 weeks prior to Week -4 Visit and/or has planned surgery or deemed likely to need surgery for Crohn's disease during the study period
- Extensive colonic resection, subtotal or total colectomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vagus Nerve Stimulation DeviceCyberonics VNS System | Device | vagus nerve stimulation |
Primary outcome
Crohn's Disease Activity Index
Time frame: Week 16
7 secondary outcomes
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
Adverse Events
Time frame: Week 16
Device Deficiencies meeting the event definition from EN ISO 14155:2011
Time frame: Week 16
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geert D'Haens, M.D., Ph.D. principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vagus Nerve Stimulation Device in people with Crohn's Disease, run by SetPoint Medical Corporation at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Croatia, Italy, Netherlands, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Crohn's Disease Activity Index (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2017.