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Crohn's DiseasePhase 3VNSNCT01569503

Vagus Nerve Stimulation a New Approach in the Treatment of Crohn's Disease

A Phase 3 study testing vagus nerve stimulation (VNS) in people with Crohn's Disease, run by University Hospital, Grenoble at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to determine whether (VNS) Vagus Nerve Stimulation , is effective in the treatment of Crohn's disease. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Crohn's Disease
What is being tested?
vagus nerve stimulation (VNS)
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteFrance
Study dates
Mar 2012to 30 May 2017
Phase
Phase 3
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with CD involving the ileo-colon, diagnosed for at least 3 months prior to screening in flare (220<CDAI<450) of their disease despite a treatment reference (corticosteroids and/or immunosuppressives) with a stable dose will be included
  • CRP>5mg/l and/or fecal calprotectin <100µg/l
  • CDEIS > 7 (Crohn's disease endoscopic index of severity)
  • Consenting patient

Who cannot join

  • Known cardiac pathology
  • VNS contraindication
  • Anoperineal CD only or associated with ileocolic lesion
  • Diagnosis of indeterminate colitis, positive stool culture for enteric pathogens
  • CD Surgery within 3 months before screening
  • Short small intestine (<1m)
Show all 13Show fewer
  • Koenig syndrome
  • Intra-abdominal abscess
  • Fistula with clinical or radiological abscess evidence
  • Anoperineal CD with or without rectal involvement
  • Ileostomy, colostomy, enteral or parenteral feeding
  • Clinical condition medically or surgically unstable that, at the discretion of the investigator would not be compatible with the patient's participation in the study
  • Any recent neoplasia, in the year prior to screening

Trial locations and contacts

1 site in 1 country.

France1 site

  • Grenoble university hospital

    Grenoble, Isere, 38043

Other trials in France

About this study

Official title: The Anti-inflammatory Effect of Vagus Nerve Stimulation (VNS): a New Approach in the Treatment of Crohn's Disease

The purpose of this study is to determine whether (VNS) Vagus Nerve Stimulation , is effective in the treatment of Crohn's disease.

Read the detailed description

Inflammatory bowel diseases or IBD (Crohn's disease and ulcerative colitis) are chronic inflammatory diseases involving the digestive tract, in particular the small bowel and/or the recto-colon. IBD represent a public health problem in Gastroenterology. The etiopathogeny of IBD is multifactorial involving immunological, genetic, infectious and environmental factors. An overarching hypothesis is that an unbalance of the autonomic nervous system, represented by the sympathetic and parasympathetic nervous system (e.g. the vagus nerve) is part of the mechanisms underlying the pathophysiology of IBD. A dysautonomia has been observed in IBD patients and we have recently demonstrated that this dysautonomia was linked to psychological coping, in particular in Crohn's disease. Classically, the vagus nerve, a mixed nerve, has an anti-inflammatory role through its central afferents which secondarily stimulate the hypothalamic-pituitary adrenal axis. Recent data have shown that the anti-inflammatory properties of the vagus nerve also involve peripheral efferents via an interaction of acetylcholine with nicotinic receptors leading to an inhibition of TNF release by macrophages. Vagus nerve stimulation (VNS) is currently used for the treatment of some forms of epilepsy in Human via a stimulation of vagal afferents. We have recently validated a model of chronic VNS (3h/d for 5 days) in freely moving rats by stimulating vagal efferents and we have studied the anti-inflammatory properties of VNS in an experimental model of colitis in rats. VNS significantly decreased body weight loss due to colitis and had an anti-inflammatory effect by decreasing a multivariate index of inflammation. To date, medical treatment of IBD (e.g. 5-aminosalicylates, corticosteroids, immunosuppressives or biotherapies i.e. anti-TNF) is only suspensive. The aim of our project is to propose another type of anti-inflammatory treatment based on neurostimulation of vagal efferents. For this purpose, we aim to perform a pilot study in 10 patients with moderate to severe Crohn's disease despite a reference treatment (corticosteroids and/or immunosuppressives) using the anti-inflammatory properties of VNS as an alternative to anti-TNF therapy. Central and peripheral effect of VNS will be also evaluated by electroencephalographic and sympatho-vagal (heart rate variability) recordings. The finality, at term, is to use VNS as an alternative to the conventional anti-TNF therapy not devoid of side effects, in particular infectious, with the advantage to use an intrinsic anti-inflammatory (anti-TNF) system and to take cover of problems of adherence to treatment which are frequently observed in the medical treatment of IBD.

Conditions
Crohn's Disease
Being tested
vagus nerve stimulation (VNS)
Keywords
Crohn's Disease, VNS, vagus nerve stimulation, inflammation, Inflammatory bowel diseases, TNF
Medical subject headings
Crohn Disease, Inflammation, Inflammatory Bowel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vagus nerve stimulation (VNS)Device

    VNS therapy consists of an implanted pacemaker-like device that delivers mild, intermittently pulsed signals to the patient's left vagus nerve. Roughly the size of a small pocket-watch and weighing less than one ounce, the pulse generator is implanted in the patient's left chest area. A thin thread-like wire, attached to the generator, runs under the skin to the left vagus nerve in the neck

Study groups in NCT01569503
Study groupRoleWhat they receive
VSNExperimentalVNS therapy
Receives: Device: vagus nerve stimulation (VNS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical remission 12 months after initiation of VNS

    Clinical remission at 12 months :

    1. Patient without corticoids or a dose of 20mg without dose adjustment (stable treatment) and without anti-TNF,
    2. CDAI <150 or CDAI has dropped by at least 70 or 100 points (Δ70, Δ100) compared with the baseline CDAI
    3. Stable immunosuppressive therapy.

    Measured: 12 months after initiation of VNS

Secondary outcomes (6)

  1. Clinical remission 6 months after initiation of VNS

    Clinical remission at 6 months :

    1. Patient without corticoids or a dose of 20mg without dose adjustment (stable treatment) and without anti-TNF,
    2. CDAI <150 or CDAI has dropped by at least 70 or 100 points (Δ70, Δ100) compared with the baseline CDAI
    3. Stable immunosuppressive therapy

    Measured: 6 months after initiation of VNS

  2. VNS tolerance

    Description and frequency of adverse events

    Measured: 12 months

  3. Assessment of VNS effectiveness with biological markers

    Assessment of VNS effectiveness with biological markers of the pro-and anti-inflammatory status

    Measured: 12 months

  4. Endoscopic and ultrasound Assessment of VNS effectiveness

    Endoscopy : CDEIS (Crohn's Disease Endoscopic Index of Severity) Ultrasound : score Migaleddu V. and al, 2009

    Measured: 12 months

  5. Assessment of the central effects of VNS

    Evolution of :

    • Sleep cycle : duration of sleep stages, sleep latency, latency between the different sleep stages.
    • High-resolution Electroencephalogram (EEG): Spatiotemporal evolution of the spectral density of EEG power in the different frequency bands
    • Correlation between high-resolution EEG markers of autonomic nervous system

    Measured: At 6 weeks, at 6 months, at 12 months

  6. Evaluation of peripheral effects of VNS on sympatho-vagal balance

    Evolution of cardiac variability markers using time and frequency analysis of electrocardiogram :

    • Frequency Analysis : LH, HF, LF/HF
    • Time analysis : RMS-SD, pNN50, NN50, average cardiac rhythm

    Measured: 6 weeks, 6 months, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2012 (estimated)
  2. Study startMar 2012
  3. Primary completion30 Mar 2017
  4. Study completion30 May 2017

Resources

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01569503
Sponsor's protocol ID
DCIC11/12
Acronym
VNS
Status last verified
Aug 2017
First submitted
30 Mar 2012
Last updated
3 May 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Meregnani J, Clarencon D, Vivier M, Peinnequin A, Mouret C, Sinniger V, Picq C, Job A, Canini F, Jacquier-Sarlin M, Bonaz B. Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease. Auton Neurosci. 2011 Feb 24;160(1-2):82-9. doi: 10.1016/j.autneu.2010.10.007. Epub 2010 Nov 11.

    PubMed 21071287

  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000 May 25;405(6785):458-62. doi: 10.1038/35013070.

    PubMed 10839541

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing vagus nerve stimulation (VNS) in people with Crohn's Disease, run by University Hospital, Grenoble at 1 site in France.

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 4 inclusion and 13 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: stopped early, as of the sponsor's last update on 3 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. 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?

Clinical remission 12 months after initiation of VNS (time frame: 12 months after initiation of VNS). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01569503, which also lists 2 linked publications.

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 May 2018.

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