Inflammatory ResponseNCT01924780
NEMOS in Normal Volunteer and JIA Study
A study testing Stimulation 10 minutes and NEMOS transvagal stimulation 60 minutes in people with Inflammatory Response, run by Karin Palmblad at 2 sites in Sweden.
Trial summary
This will be a two-stage study to test whether t-VNS using the NEMOS device can activate the CAP and reduce markers of systemic inflammation. Stage A (healthy volunteers) stage B (patients with Juvenile Idiopathic Arthritis). Stage A: healthy human volunteers. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Response
- What is being tested?
- Stimulation 10 minutes and NEMOS transvagal stimulation 60 minutes
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 2 sitesSweden
- Study dates
- Aug 2013to Jul 2014
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed informed consent
- Males and females ages 18-75, inclusive
- Subjects must be free from any active disease, and must not be on any medication that, in the opinion of the investigator, might compromise the measurement or interpretation of the study biomarkers
- Subjects must be able to attend all study visits
Who cannot join
- Significant psychiatric disease or substance abuse
- Anatomic abnormalities, wounds, significant scars or skin disorders affecting the left pinna or external ear canal which would hinder the safe and proper use of the study device
- History of unilateral or bilateral vagotomy
- History of recurrent vasovagal syncope episodes
- Women who are pregnant or plan to conceive during the study. Women of childbearing potential must be willing to use a reliable form of birth control during the study.
- Known history of cardiac rhythm disturbances, atrioventricular block of greater than first degree, or cardiac conduction pathway abnormalities other than isolated right bundle branch block or isolated left anterior fascicle block
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- Presence of previously implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators), or plans to implant such devices during the course of the study
- Planned use of any other external electrically active medical device during the course of the study (e.g., transcutaneous electrical nerve stimulation [TENS] units)
- Any investigational small molecule drug within 30 days of Day 0, visit investigational monoclonal antibody or soluble receptor within 3 months of Day 0 visit
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Astrid Lindgrens Childrens Hospital, Karolinska University Hospital,
Stockholm, Solna, 171 76
Astrid Lindgren University Hospital
Stockholm, Stockholm County, 17176
About this study
Official title: Evaluation of the Anti-inflammatory Potential of NEMOS® Transcutaneous Vagus Nerve Stimulation Device in Patients With Juvenile Idiopathic Arthritis
This will be a two-stage study to test whether t-VNS using the NEMOS device can activate the CAP and reduce markers of systemic inflammation. Stage A (healthy volunteers) stage B (patients with Juvenile Idiopathic Arthritis).
Stage A: healthy human volunteers. A randomized, single blind, three-period crossover design comparing the CAP activation effect of 10 minutes (active) versus 60 minutes (active) versus 10 minutes (sham) stimulation with the NEMOS device. CAP activation will be assessed by reduction in the in vitro release of LPS-inducible cytokines from whole blood.
Read more
Analysis of the reduction in whole blood cytokine release assay after 10 versus 60 minutes of stimulation, and the kinetics of the nadir of the whole blood cytokine release assay will inform the selection of dose duration and sampling time for Stage B. Performing this more extensive exploration of dose duration and kinetics in adults will allow one dose, and a single optimal sampling time in the JIA patients, thus minimizing blood drawing and discomfort in these children.
Stage B will be performed in patients with JIA. This will be an open label design examining the effect of the optimal dose duration (either 10 minutes or 60 minutes of stimulation, as determined by results of Stage A). All information regarding Stage B will be registered in a separate registration at clincialtrials.gov. in order to keep accuracy. All details below concerns only Stage A.
Read the detailed description
The vagus nerve mediates the "inflammatory reflex"; a mechanism the central nervous system utilizes to regulate innate and adaptive immunity (Andersson, 2012). The afferent arm of the reflex senses inflammation both peripherally and in the central nervous system, and down-regulates the inflammation via efferent neural outflow. The efferent arm of this reflex has been termed the "cholinergic anti-inflammatory pathway" (CAP). The reflex serves as a physiological regulator of inflammation by responding to environmental injury and pathogens with an appropriate degree of immune system activation An increasing body of evidence indicates that the CAP can also be harnessed to reduce pathological inflammation. Electrical neurostimulation of the vagus nerve (VNS) with either a surgically implantable device, or alternatively using a non-invasive device that stimulates the auricular branch of the vagus nerve (ABVN) may be a feasible means of modulating diseases characterized by excessive and dysregulated inflammation.
- Conditions
- Inflammatory Response
- Being tested
- Stimulation 10 minutes, NEMOS transvagal stimulation 60 minutes, NEMOS Device sham stimulation 10 minutes
- Keywords
- Dose-Response Relationship, Immunologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stimulation 10 minutesDevice
NEMOS transvagal stimuli 10 minutes
NEMOS transvagal stimulation 60 minutesDevice
NEMOS Device stimulation in 60 minutes
NEMOS Device sham stimulation 10 minutesDevice
| Study group | Role | What they receive |
|---|---|---|
| NEMOS device stimulation 10 minutes | Active comparator | Subject will be stimulated in the cymba concha with a vibro-tactile mechanical device for 10 minutes Receives: Device: Stimulation 10 minutes; Device: NEMOS transvagal stimulation 60 minutes; Device: NEMOS Device sham stimulation 10 minutes |
| NEMOS device 60 minutes stimulation | Active comparator | Subjects will be stimulated in the cymba concha with a vibro-tactile mechanical device for 60 minutes Receives: Device: Stimulation 10 minutes; Device: NEMOS transvagal stimulation 60 minutes; Device: NEMOS Device sham stimulation 10 minutes |
| Sham 10 minutes | Sham comparator | 10 minutes of t-VNS stimulation by rotating the NEMOS ear electrode 180 degrees within the pinna, which will position the electrode on the earlobe Receives: Device: Stimulation 10 minutes; Device: NEMOS transvagal stimulation 60 minutes; Device: NEMOS Device sham stimulation 10 minutes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-inflammatory Pharmacokinetics
Determine if CAP can be evoked and set the maximum percent change in the in vitro release of LPS-inducible TNF in the whole blood in vitro LPS-inducible cytokine release assay, over the interval from pre-t-VNS to 7 days following t-VNS, comparing sham treatment to each of the two active treatment groups, i.e. 10 minutes and 60 minutes
Measured: 3 months
Secondary outcomes (3)
Anti-inflammatory response
Determine whether 60 minutes of t-VNS induces greater reduction and/or longer duration of effect than 10 minutes as assessed by the in vitro release of LPS-inducible TNF from whole blood
Measured: 3 months
Anti inflammatory response
-Determine the optimum time point for blood sampling the in vitro release of LPS-inducible TNF from whole blood as assessed by the time of nadir post-stimulation
Measured: 3 months
Anti-inflammatory response
Determine the effect of t-VNS on the in vitro release of LPS-inducible IL-1 and IL-6 from whole blood
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2013 (estimated)
- Study startAug 2013
- Primary completionJun 2014 (estimated)
- Study completionJul 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory ResponseStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karin Palmblad
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet
- Responsible party
- Sponsor-investigator, Karin Palmblad, Astrid Lindgren Children´s Hospital
- Investigators
- Ulf Andersson, Professor, Study chair, Department of Women´s and Children´s Health | Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01924780
- Sponsor's protocol ID
- NEMOS1
- Status last verified
- Sep 2013
- First submitted
- 12 Aug 2013
- Last updated
- 9 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Anti-inflammatory Potential of NEMOS® Transcutaneous Vagus Nerve Stimulation Device in Patients With Juvenile Idiopathic Arthritis
- ClinicalTrials.gov ID
- NCT01924780
- Acronym / sponsor ID
- NEMOS1
- Conditions
- Inflammatory Response
- Keywords
- Dose-Response Relationship, Immunologic
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Karin PalmbladUniversity, hospital or other
- Collaborators
- Karolinska Institutet
- Study start
- Aug 2013
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Jul 2014 (estimated)
- First posted
- 16 Aug 2013 (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 will be a two-stage study to test whether t-VNS using the NEMOS device can activate the CAP and reduce markers of systemic inflammation. Stage A (healthy volunteers) stage B (patients with Juvenile Idiopathic Arthritis).
Stage A: healthy human volunteers. A randomized, single blind, three-period crossover design comparing the CAP activation effect of 10 minutes (active) versus 60 minutes (active) versus 10 minutes (sham) stimulation with the NEMOS device. CAP activation will be assessed by reduction in the in vitro release of LPS-inducible cytokines from whole blood.
Analysis of the reduction in whole blood cytokine release assay after 10 versus 60 minutes of stimulation, and the kinetics of the nadir of the whole blood cytokine release assay will inform the selection of dose duration and sampling time for Stage B. Performing this more extensive exploration of dose duration and kinetics in adults will allow one dose, and a single optimal sampling time in the JIA patients, thus minimizing blood drawing and discomfort in these children.
Stage B will be performed in patients with JIA. This will be an open label design examining the effect of the optimal dose duration (either 10 minutes or 60 minutes of stimulation, as determined by results of Stage A). All information regarding Stage B will be registered in a separate registration at clincialtrials.gov. in order to keep accuracy. All details below concerns only Stage A.
Detailed description
The vagus nerve mediates the "inflammatory reflex"; a mechanism the central nervous system utilizes to regulate innate and adaptive immunity (Andersson, 2012). The afferent arm of the reflex senses inflammation both peripherally and in the central nervous system, and down-regulates the inflammation via efferent neural outflow. The efferent arm of this reflex has been termed the "cholinergic anti-inflammatory pathway" (CAP). The reflex serves as a physiological regulator of inflammation by responding to environmental injury and pathogens with an appropriate degree of immune system activation An increasing body of evidence indicates that the CAP can also be harnessed to reduce pathological inflammation. Electrical neurostimulation of the vagus nerve (VNS) with either a surgically implantable device, or alternatively using a non-invasive device that stimulates the auricular branch of the vagus nerve (ABVN) may be a feasible means of modulating diseases characterized by excessive and dysregulated inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NEMOS device stimulation 10 minutes | Active comparator | Device: Stimulation 10 minutes, Device: NEMOS transvagal stimulation 60 minutes, Device: NEMOS Device sham stimulation 10 minutesSubject will be stimulated in the cymba concha with a vibro-tactile mechanical device for 10 minutes |
| NEMOS device 60 minutes stimulation | Active comparator | Device: Stimulation 10 minutes, Device: NEMOS transvagal stimulation 60 minutes, Device: NEMOS Device sham stimulation 10 minutesSubjects will be stimulated in the cymba concha with a vibro-tactile mechanical device for 60 minutes |
| Sham 10 minutes | Sham comparator | Device: Stimulation 10 minutes, Device: NEMOS transvagal stimulation 60 minutes, Device: NEMOS Device sham stimulation 10 minutes10 minutes of t-VNS stimulation by rotating the NEMOS ear electrode 180 degrees within the pinna, which will position the electrode on the earlobe |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Signed informed consent
- Males and females ages 18-75, inclusive
- Subjects must be free from any active disease, and must not be on any medication that, in the opinion of the investigator, might compromise the measurement or interpretation of the study biomarkers
- Subjects must be able to attend all study visits
Key exclusion criteria (9 listed)
- Significant psychiatric disease or substance abuse
- Anatomic abnormalities, wounds, significant scars or skin disorders affecting the left pinna or external ear canal which would hinder the safe and proper use of the study device
- History of unilateral or bilateral vagotomy
- History of recurrent vasovagal syncope episodes
- Women who are pregnant or plan to conceive during the study. Women of childbearing potential must be willing to use a reliable form of birth control during the study.
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 |
|---|---|---|
| Stimulation 10 minutesNEMOS transvagal stimuli 10 minutes | Device | NEMOS device 60 minutes stimulation, NEMOS device stimulation 10 minutes, Sham 10 minutes |
| NEMOS transvagal stimulation 60 minutesNEMOS Device stimulation in 60 minutes | Device | NEMOS device 60 minutes stimulation, NEMOS device stimulation 10 minutes, Sham 10 minutes |
| NEMOS Device sham stimulation 10 minutes | Device | NEMOS device 60 minutes stimulation, NEMOS device stimulation 10 minutes, Sham 10 minutes |
Primary outcome
Anti-inflammatory Pharmacokinetics
Time frame: 3 months
Determine if CAP can be evoked and set the maximum percent change in the in vitro release of LPS-inducible TNF in the whole blood in vitro LPS-inducible cytokine release assay, over the interval from pre-t-VNS to 7 days following t-VNS, comparing sham treatment to each of the two active treatment groups, i.e. 10 minutes and 60 minutes
3 secondary outcomes
Anti-inflammatory response
Time frame: 3 months
Anti inflammatory response
Time frame: 3 months
Anti-inflammatory response
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2013.
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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.
Ulf Andersson, Professor study chair
Department of Women´s and Children´s Health | Karolinska Institutet
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stimulation 10 minutes and NEMOS transvagal stimulation 60 minutes in people with Inflammatory Response, run by Karin Palmblad at 2 sites in Sweden.
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 9 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 9 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in 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. Some participants in this study may receive a placebo. 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?
Anti-inflammatory Pharmacokinetics (time frame: 3 months). 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 9 Sep 2013.