Systemic Lupus ErythematosusPhase 2TRUSTNCT02917265
Transcutaneous Vagus Nerve Stimulation for the Treatment of Lupus
A Phase 2 study testing TENS for vagus stimulation in people with Systemic Lupus Erythematosus, run by Aikaterini Thanou at 1 site in United States.
Trial summary
This is a 3-month double blinded randomized controlled study of transcutaneous electrical vagus nerve stimulation (tVNS) compared to a sham stimulation for the treatment of patients with active systemic lupus erythematosus (SLE). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- TENS for vagus stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with SLE age 18-70 meeting the American College of Rheumatology Classification Criteria. Patients need to meet a minimum of 4 out of 11 criteria simultaneously or serially on two separate occasions.
- Positive antinuclear antibody or anti-dsDNA within one year of screening
- Non-serological SLEDAI ≥4 or ≥1 BILAG B or A and presence of inflammatory arthritis (defined by at least 3 swollen and 3 tender joints) at screening
- Patients may receive on one or more of the following immune suppressive therapies: hydroxychloroquine, quinacrine, methotrexate, azathioprine, mycophenolate mofetil, tacrolimus, sirolimus, belimumab, abatacept. Immune suppressive medications should have been administered at stable doses for ≥30 days prior to baseline. Patients may also be on prednisone up to 10mg daily or equivalent steroid treatment at the baseline visit.
Who cannot join
- Acute lupus nephritis defined as class II,III, IV or V nephritis diagnosed within 6 months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
- Active CNS lupus affecting mental status
- Any other organ threatening or life threatening manifestation of SLE as well as those, who, in the opinion of the investigator, have severe multi-organ or refractory lupus
- Rituximab treatment within 6 months prior to screening and/or without return of B cells to baseline levels
- Treatment with cyclophosphamide within a month prior to screening
- Treatment with any investigational drug within 3 months or 5 half-lives whichever is longer
Show all 21Show fewer
- Recurrent vaso-vagal syncopal episodes
- Unilateral or bilateral vagotomy
- Presence of any evidence of vagus nerve pathology or injury
- Heart failure (NYHA class III or IV)
- Known atherosclerotic disease, including severe carotid artery disease, uncontrolled hypertension, uncontrolled diabetes, and history of myocardial infarction (MI), cardiomyopathy or stroke within the past year. Clinically stable patients with coronary artery disease, but no recent MI (within the past year) and no current symptoms of angina are not however excluded.
- Valvular and other structural heart disease that is evident by transthoracic echocardiogram and is associated with heart failure (NYHA class III or IV)
- Prolonged QT interval or abnormal baseline ECG - sick sinus syndrome, Mobitz type 2 second or third degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation or clinically significant premature ventricular contraction
- Individuals currently implanted with an electrical and/or neurostimulator device, such as cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant
- Known respiratory disease that has decreased any pulmonary function test more than 25% below expected values or has resulted in hospitalization within the past year
- All diagnosed syndromes affecting the central nervous system (CNS) or autonomic nervous system
- Major psychiatric disorders including evidence of major depressive disorder (DSM-5 diagnostic criteria) that is not currently controlled by medications
- Hemoglobin below 9.0 gm/dL (by the most recent CBC)
- Pregnancy or breast feeding
- Inability or unwillingness to understand and/or sign informed consent
- Any other medical condition, whether or not related to lupus, which, in the opinion of the investigator, would render the patient inappropriate or too unstable to complete the study protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, 73104
About this study
Official title: Transcutaneous Vagus Nerve Stimulation for the Treatment of Systemic Lupus Erythematosus
This is a 3-month double blinded randomized controlled study of transcutaneous electrical vagus nerve stimulation (tVNS) compared to a sham stimulation for the treatment of patients with active systemic lupus erythematosus (SLE).
Read the detailed description
Patients with SLE and active, non-organ-threatening disease are eligible to participate in this prospective randomized double blind trial of active or sham transcutaneous electrical vagus nerve stimulation (tVNS). Active tNVS is performed by the use of a transcutaneous electrical nerve stimulation (TENS) device with electrodes attached to an area of the external ear innervated by the auricular branch of the vagus nerve. The same protocol is followed in the sham tVNS arm, but the pads are placed on an area of the external ear that is devoid of vagus innervation.TENS is applied for 60 to 120 minutes daily as tolerated and participants keep a detailed log of their daily TENS sessions. Patients return to clinic at weeks 4, 8 and 12 for study related assessments.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- TENS for vagus stimulation, TENS for sham stimulation
- Keywords
- vagus nerve stimulation, systemic lupus erythematosus
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TENS for vagus stimulationDevice
TENS electrodes are applied on an area of the external ear innervated by the auricular branch of the vagus nerve.
TENS for sham stimulationDevice
TENS electrodes are applied on an area of the external ear devoid of vagus innervation.
| Study group | Role | What they receive |
|---|---|---|
| TENS for vagus stimulation | Experimental | A transcutaneous electrical nerve stimulation (TENS) unit is applied to an area of the external ear that is innervated by the auricular branch of the vagus nerve. Receives: Device: TENS for vagus stimulation |
| TENS for sham stimulation | Sham comparator | A TENS unit is applied to an area of the external ear that is devoid of vagus innervation. Receives: Device: TENS for sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the BILAG-based Combined Lupus Assessment (BICLA)
Achieving a BICLA response requires to meet all of the following parameters:
- All British Isles Lupus Assessment Group (BILAG) A scores improving to B/C/D and all BILAG level B scores improving to C/D
- No single new BILAG A \& not >1 new BILAG B scores, no worsening of the baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score AND no worsening in the Physician Global Assessment (PGA) (<10% worsening from baseline)
- No initiation of non-protocol treatments or premature study discontinuation
The range of values for the above instruments are listed below, with higher scores indicating more active disease:
BILAG: 0 to 96 SLEDAI: 0 to 105 PGA: 0-3
Measured: 12 weeks
Secondary outcomes (2)
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the Systemic Lupus Erythematosus Responder Index (SRI-4)
SRI requires meeting all of the following parameters:
- ≥4-point reduction from baseline in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score
- No single new British Isles Lupus Assessment Group (BILAG) A score \& not >1 new BILAG B scores AND no worsening in the Physician Global Assessment (PGA) (<10% worsening from baseline)
- No initiation of non-protocol treatments or premature study discontinuation
The range of values for the above instruments are listed below, with higher scores indicating more active disease:
BILAG: 0 to 96 SLEDAI: 0 to 108 PGA: 0-3
Measured: 12 weeks
Percentage of Participants on Active vs Sham tVNS With Improvement in Heart Rate Variability (HRV)
HRV is measured by time domain (RMSSD and pNN50) and frequency domain [high frequency (HF), low to high frequency (LF/HF) ratio] parameters.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2016 (estimated)
- Study startNov 2015
- Primary completionMay 2017
- Study completionNov 2018
Why it stopped: poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Systemic Lupus ErythematosusStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aikaterini Thanou
- Collaborators
- Oklahoma Medical Research Foundation, University of Oklahoma
- Responsible party
- Principal investigator, Aikaterini Thanou, Oklahoma Medical Research Foundation
- Investigators
- Aikaterini Thanou, MD, Principal investigator, Oklahoma Medical Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02917265
- Sponsor's protocol ID
- H15-141
- Acronym
- TRUST
- Status last verified
- Sep 2019
- First submitted
- 28 Mar 2016
- Last updated
- 3 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Vagus Nerve Stimulation for the Treatment of Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT02917265
- Acronym / sponsor ID
- TRUST / H15-141
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- vagus nerve stimulation, systemic lupus erythematosus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor recruitment
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Aikaterini Thanou
- Collaborators
- Oklahoma Medical Research Foundation, University of Oklahoma
- Study start
- Nov 2015 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 28 Sep 2016 (estimated)
- Results
- Posted 10 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 3-month double blinded randomized controlled study of transcutaneous electrical vagus nerve stimulation (tVNS) compared to a sham stimulation for the treatment of patients with active systemic lupus erythematosus (SLE).
Detailed description
Patients with SLE and active, non-organ-threatening disease are eligible to participate in this prospective randomized double blind trial of active or sham transcutaneous electrical vagus nerve stimulation (tVNS). Active tNVS is performed by the use of a transcutaneous electrical nerve stimulation (TENS) device with electrodes attached to an area of the external ear innervated by the auricular branch of the vagus nerve. The same protocol is followed in the sham tVNS arm, but the pads are placed on an area of the external ear that is devoid of vagus innervation.TENS is applied for 60 to 120 minutes daily as tolerated and participants keep a detailed log of their daily TENS sessions. Patients return to clinic at weeks 4, 8 and 12 for study related assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TENS for vagus stimulation | Experimental | Device: TENS for vagus stimulationA transcutaneous electrical nerve stimulation (TENS) unit is applied to an area of the external ear that is innervated by the auricular branch of the vagus nerve. |
| TENS for sham stimulation | Sham comparator | Device: TENS for sham stimulationA TENS unit is applied to an area of the external ear that is devoid of vagus innervation. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with SLE age 18-70 meeting the American College of Rheumatology Classification Criteria. Patients need to meet a minimum of 4 out of 11 criteria simultaneously or serially on two separate occasions.
- Positive antinuclear antibody or anti-dsDNA within one year of screening
- Non-serological SLEDAI ≥4 or ≥1 BILAG B or A and presence of inflammatory arthritis (defined by at least 3 swollen and 3 tender joints) at screening
- Patients may receive on one or more of the following immune suppressive therapies: hydroxychloroquine, quinacrine, methotrexate, azathioprine, mycophenolate mofetil, tacrolimus, sirolimus, belimumab, abatacept. Immune suppressive medications should have been administered at stable doses for ≥30 days prior to baseline. Patients may also be on prednisone up to 10mg daily or equivalent steroid treatment at the baseline visit.
Key exclusion criteria (21 listed)
- Acute lupus nephritis defined as class II,III, IV or V nephritis diagnosed within 6 months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
- Active CNS lupus affecting mental status
- Any other organ threatening or life threatening manifestation of SLE as well as those, who, in the opinion of the investigator, have severe multi-organ or refractory lupus
- Rituximab treatment within 6 months prior to screening and/or without return of B cells to baseline levels
- Treatment with cyclophosphamide within a month prior to screening
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 |
|---|---|---|
| TENS for vagus stimulationTENS electrodes are applied on an area of the external ear innervated by the auricular branch of the vagus nerve. | Device | TENS for vagus stimulation |
| TENS for sham stimulationTENS electrodes are applied on an area of the external ear devoid of vagus innervation. | Device | TENS for sham stimulation |
Primary outcome
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the BILAG-based Combined Lupus Assessment (BICLA)
Time frame: 12 weeks
Achieving a BICLA response requires to meet all of the following parameters: 1. All British Isles Lupus Assessment Group (BILAG) A scores improving to B/C/D and all BILAG level B scores improving to C/D 2. No single new BILAG A \& not >1 new BILAG B scores, no worsening of the baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score AND no worsening in the Physician Global Assessment (PGA) (<10% worsening from baseline) 3. No initiation of non-protocol treatments or premature study discontinuation The range of values for the above instruments are listed below, with higher scores indicating more active disease: BILAG: 0 to 96 SLEDAI: 0 to 105 PGA: 0-3
2 secondary outcomes
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the Systemic Lupus Erythematosus Responder Index (SRI-4)
Time frame: 12 weeks
Percentage of Participants on Active vs Sham tVNS With Improvement in Heart Rate Variability (HRV)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Aikaterini Thanou, MD principal investigator
Oklahoma Medical Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TENS for vagus stimulation in people with Systemic Lupus Erythematosus, run by Aikaterini Thanou at 1 site in United States.
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 21 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 Mar 2020. 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the BILAG-based Combined Lupus Assessment (BICLA) (time frame: 12 weeks). 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 Mar 2020.