NCT01924780

Brief 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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
12

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Aug 2013

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2013

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

August 12, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 16, 2013

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2014

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
Last Updated

September 9, 2013

Status Verified

September 1, 2013

Enrollment Period

10 months

First QC Date

August 12, 2013

Last Update Submit

September 6, 2013

Conditions

Inflammatory Response

Keywords

Dose-Response Relationship, Immunologic

Outcome Measures

Primary Outcomes (1)

  • 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

    3 months

Secondary Outcomes (3)

  • Anti-inflammatory response

    3 months

  • Anti inflammatory response

    3 months

  • Anti-inflammatory response

    3 months

Study Arms (3)

NEMOS device stimulation 10 minutes

ACTIVE COMPARATOR

Subject will be stimulated in the cymba concha with a vibro-tactile mechanical device for 10 minutes

Device: Stimulation 10 minutesDevice: NEMOS transvagal stimulation 60 minutesDevice: 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

Device: Stimulation 10 minutesDevice: NEMOS transvagal stimulation 60 minutesDevice: 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

Device: Stimulation 10 minutesDevice: NEMOS transvagal stimulation 60 minutesDevice: NEMOS Device sham stimulation 10 minutes

Interventions

Stimulation 10 minutesDEVICE

NEMOS transvagal stimuli 10 minutes

NEMOS device 60 minutes stimulationNEMOS device stimulation 10 minutesSham 10 minutes
NEMOS transvagal stimulation 60 minutesDEVICE

NEMOS Device stimulation in 60 minutes

NEMOS device 60 minutes stimulationNEMOS device stimulation 10 minutesSham 10 minutes
NEMOS Device sham stimulation 10 minutesDEVICE
NEMOS device 60 minutes stimulationNEMOS device stimulation 10 minutesSham 10 minutes

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Astrid Lindgrens Childrens Hospital, Karolinska University Hospital,

Stockholm, Solna, 171 76, Sweden

Location

Astrid Lindgren University Hospital

Stockholm, Stockholm County, 17176, Sweden

Location

Study Officials

  • Ulf Andersson, Professor

    Department of Women´s and Children´s Health | Karolinska Institutet

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
M.D. PhD Senior scientist

Study Record Dates

First Submitted

August 12, 2013

First Posted

August 16, 2013

Study Start

August 1, 2013

Primary Completion

June 1, 2014

Study Completion

July 1, 2014

Last Updated

September 9, 2013

Record last verified: 2013-09

Locations

SE(2)