Systemic Lupus ErythematosusPhase 2TvSSLENCT06987565
Transcutaneous Vagus Nerve Stimulation in SLE
A Phase 2 study testing Active vagus nerve stimulation in people with Systemic Lupus Erythematosus, run by Northwell Health at 1 site in United States.
Trial summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Joint and muscle pain and fatigue are extremely common among patients and contribute to a reduced quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Active vagus nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jul 2025to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- SLE (defined by the ACR or SLICC criteria),
- Musculoskeletal pain ≥ 4 on a non-anchored VAS 10 cm scale,
- BILAG C or greater on the Musculoskeletal Domain of the BILAG 2004,
- If on corticosteroids, the dose must be stable and ≤ 10 mg/day (prednisone or equivalent) for at least 14 days before baseline,
- If on background immunosuppressive treatment the dose must be stable for at least 28 days before baseline,
- If on NSAIDS, the dose must be stable for at least 7 days before baseline and the subject must be willing not to change the dose during the trial (except for toxicity),
- Able and willing to give written informed consent and comply with the requirements of the study protocol.
Who cannot join
- Initiation of immunosuppressive or antimalarial treatment within 3 months of baseline,
- Treatment with cyclophosphamide within 2 months of baseline,
- Initiation of anifrolumab within 3 months of baseline
- Initiation of belimumab within 6 months of baseline,
- Expectation to increase steroids and/or immunosuppressive treatment,
- Anti-phospholipid syndrome,
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- Fibromyalgia,
- Treatment with an anti-cholinergic medication, including over the counter medications,
- Any implantable electronic devices including pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators,
- Current tobacco or nicotine user (to limit potential confounding effects of exposure to nicotine),
- Joint replacement within 60 days prior to study enrollment or planned within the course of the study,
- Any planned surgical procedure requiring general anesthesia within the course of the study,
- Intra-articular cortisone injections within 28 days of the start of study,
- Chronic inflammatory disorders apart from SLE affecting the joints,
- Investigational drug and/or treatment during the 28 days or seven half-lives of the investigational drug prior to the start of study drug dosing (Day 0), whichever is the greater length of time,
- Active infection including hepatitis B or hepatitis C at baseline,
- Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention,
- Pregnancy or lactation (Pregnancy status will be determined via serum blood test \& lactation will be determined via self-report),
- Comorbid disease that has previously required administration of corticosteroid use,
- Known allergy to mannitol or lactulose,
- Chronic treatment with narcotic medication,
- Prior receipt of transauricular vagus nerve stimulation in a clinical trial,
- Inability to comply with study and follow-up procedures.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Feinstein Institutes for Medical Research
Manhasset, New York, 11030
Sanita Kandasami, 516-562-2401, skandasami@northwell.edu
Cynthia Aranow, MD, 516 562-3845, caranow@northwell.edu
About this study
Official title: Transcutaneous Vagus Nerve Stimulation in SLE (TvSSLE)
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Joint and muscle pain and fatigue are extremely common among patients and contribute to a reduced quality of life. Available therapies may be associated with significant side effects and many patients do not achieve an adequate response to these treatments. Therefore, there is an unmet need to develop new strategies to reduce pain and fatigue. Filling this need would significantly improve patients' quality of life. This trial will evaluate the effects of a novel approach, stimulating the vagus nerve, a nerve originating in the brain as a potential therapeutic intervention for treatment of musculoskeletal pain and fatigue. Vagus nerve stimulation has multiple beneficial effects and is one of the body's own ways to modulate the immune system. One can stimulate the vagus nerve via the skin at the neck or at specific locations in the ear, (transcutaneous vagus nerve stimulation: tcVNS). We recently completed a short, small scale randomized, placebo controlled trial of tcVNS in patients with SLE and observed dramatic benefits on musculoskeletal pain and fatigue. The treatment was safe without side effects. We are therefore proposing a longer trial to validate our initial findings and to look at durability. In this study, 18 patients with musculoskeletal pain will be followed for 2 months and will receive tcVNS or placebo (sham stimulation) for 5 minutes/day for 28 days. Patients will have a 1 out of 3 chance of receiving sham stimulation and neither the patient nor the evaluating investigator will know the actual treatment. The stimulations are self-administered, are non-painful and have not been associated with serious risks. After 28 days of stimulation, treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate durability. Pain, fatigue and disease activity will be evaluated as well as possible side effects will be monitored throughout the trial. This study will also explore biologic mechanisms that may be responsible for the potential clinical effects. This will include possible effects of stimulation on gut permeability and the stool microbiome, areas that may play a significant role contributing to SLE disease and its manifestations. The development of an effective treatment without significant side effects would be extremely valuable and a significant advance for patients with SLE. If efficacious, tcVNS offers a non-toxic, non-immunosuppressive strategy to control two of the most common symptoms of this disease.
Read the detailed description
Musculoskeletal (MS) pain and fatigue are common symptoms of patients with Systemic Lupus Erythematosus (SLE) affecting up to 95% and contributing to a reduced quality of life. Safe and efficacious treatment remains an unmet need for these disease manifestations. Stimulation of the vagus nerve results in beneficial effects in patients. We recently completed a short , small scale, randomized, sham-controlled, double blind clinical trial of transcutaneous vagus nerve stimulation (taVNS) in patients with SLE. The clinical benefit on MS pain and fatigue was dramatic. We now propose a randomized sham controlled clinical trial assessing the efficacy and durability of a longer exposure to taVNS (28 days in comparison to the 4 day exposure in the previous trial) in 18 patients randomized 2: 1 with musculoskeletal pain. After 28 days of stimulation, the treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate the treatment's durability. Pain, fatigue, disease activity (global and musculoskeletal) and safety will be evaluated and safety will be monitored throughout the trial. In this clinical trial we will also explore potential biologic mechanisms and pathways by which taVNS exerts ifs effects in SLE, including potential effects on gut permeability and the microbiome.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Active vagus nerve stimulation, Sham vagus nerve stimulation
- Keywords
- Systemic Lupus Erythematosus, Pain, Vagus nerve stimulation
- Medical subject headings
- Lupus Erythematosus, Systemic, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active vagus nerve stimulationDevice
Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated. Patients will be followed through day 57 to assess durability of the intervention.
Sham vagus nerve stimulationDevice
Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated, however, the vagus nerve will not be stimulated. Patients will be followed through day 57 to assess durability of the intervention.
| Study group | Role | What they receive |
|---|---|---|
| Vagus Nerve Stimulation | Active comparator | Patients will receive transcutaneous stimulation of the left vagus nerve for 5 minutes daily for 28 consecutive days. Receives: Device: Active vagus nerve stimulation |
| Sham Vagus Nerve Stimulation | Placebo comparator | Patients will receive sham transcutaneous stimulation of the of the left vagus nerve for 5 minutes daily for 28 consecutive days. Receives: Device: Sham vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Musculoskeletal Pain From Baseline.
Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain.
Measured: 28 days
Secondary outcomes (75)
Percentage of Subjects With Treatment Emergent Adverse Events.
The percentage of participants with grade 2 or higher or specific grade 1 treatment emergent adverse events will be assessed using the NCI-CTAEversion4.
The percentage of participants with grade 2 or higher treatment emergent adverse events will be assessed using the NCI-CTAEversion4.
The percentage of participants with grade 2 or higher treatment emergent adverse events will be assessed using the NCI-CTAEversion4.
Measured: 57 days
Change in Musculoskeletal Pain From Baseline
Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain.
Measured: 5 days
Change in Musculoskeletal Pain From Baseline
Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain.
Measured: 57 days
Change in Musculoskeletal Pain From Day 29 to Day 57
Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain.
Measured: day 29 to day 57
Fatigue
Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue.
Measured: 5 days
Fatigue
Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue.
Measured: 28 days
Fatigue
Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue.
Measured: 57 days
Fatigue
Change from Day 29 fatigue to Day 57 will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue.
Measured: day 29 to day 57
Tender Joint Reduction
The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.
Measured: 5 days
Tender Joint Reduction
The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.
Measured: 28 days
Tender Joint Reduction
The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.
Measured: 57 days
Tender Joint Reduction
The percentage of tender joints reduced from day 29 to day 57 will be assessed by an investigator upon examining 68 potential tender joints.
Measured: Day 29 to Day 57
Swollen joint reduction
The percentage of swollen joints reduced from baseline assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline.
Measured: 5 days
Swollen joint reduction
The percentage of swollen joints reduced from baseline assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline.
Measured: 28 days
Swollen joint reduction
The percentage of swollen joints reduced from baseline assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline.
Measured: 57 days
Swollen joint reduction
The percentage of swollen joints reduced from Day 29 to Day 57 assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline.
Measured: Day 29 to Day 57
Physician Global Assessment of Disease Activity (PGA)
Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.
Measured: Day 5
Physician Global Assessment of Disease Activity (PGA)
Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.
Measured: Day 28
Physician Global Assessment of Disease Activity (PGA)
Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.
Measured: Day 57
Physician Global Assessment of Disease Activity (PGA)
Change in PGA from day 29 to day 57; PGA is an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.
Measured: Days 29 to 57
Patient Global Assessment of Disease (PtGA)
Change in PtGA from baseline, an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity.
Measured: Day 5
Patient Global Assessment of Disease (PtGA)
Change in PtGA from baseline, an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity.
Measured: Day 28
Patient Global Assessment of Disease (PtGA)
Change in PtGA from baseline, an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity.
Measured: Day 57
Patient Global Assessment of Disease (PtGA)
Change in PtGA from day 29 to 57; PtGA is an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity.
Measured: Days 29 to 57
Pain intensity
Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity.
Measured: 5 days
Pain intensity
Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity.
Measured: 28 days
Pain intensity
Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity.
Measured: 57 days
Pain intensity
Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity.
Measured: Days 29 to 57
Pain interference
Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days
Measured: 5 days
Pain interference
Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days
Measured: 28 days
Pain interference
Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days
Measured: 57 days
Pain interference
Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days
Measured: Days 29 to 57
Health Related Quality of Life (HRQoL))
HRQoL will be evaluated using the LupusQoL, a validated SLE specific index which assesses 8 domains including physical health, emotional health, body image, pain, planning, fatigue, intimate relationships, and burden to others. Higher scores correspond to worse quality-of-life.
Measured: 28 days
Health Related Quality of Life (HRQoL))
HRQoL will be evaluated using the LupusQoL, a validated SLE specific index which assesses 8 domains including physical health, emotional health, body image, pain, planning, fatigue, intimate relationships, and burden to others. Higher scores correspond to worse quality-of-life.
Measured: Day 57
Health Related Quality of Life (HRQoL))
HRQoL will be evaluated using the LupusQoL, a validated SLE specific index which assesses 8 domains including physical health, emotional health, body image, pain, planning, fatigue, intimate relationships, and burden to others. Higher scores correspond to worse quality-of-life.
Measured: Days 29 to 57
Anxiety
Promis Anxiety Short Form will assess anxiety. It is an 8 item questionaire assessing components related to anxiety including fear, anxious misery, hyperarousal, and somatic symptoms. Higher scores indicate greater levels of anxiety.
Measured: Day 29
Anxiety
Promis Anxiety Short Form will assess anxiety. It is an 8 item questionaire assessing components related to anxiety including fear, anxious misery, hyperarousal, and somatic symptoms. Higher scores indicate greater levels of anxiety.
Measured: Day 57
Anxiety
Promis Anxiety Short Form will assess anxiety. It is an 8 item questionaire assessing components related to anxiety including fear, anxious misery, hyperarousal, and somatic symptoms. Higher scores indicate greater levels of anxiety.
Measured: Days 29 to 57
Depression
Beck Depression Inventory (BDI) will assess depression. The BDI is a 21 item questionnaire measuring the severity of depression. Higher scores indicate greater levels of depression.
Measured: Day 28
Depression
Beck Depression Inventory (BDI) will assess depression. The BDI is a 21 item questionnaire measuring the severity of depression. Higher scores indicate greater levels of depression.
Measured: Day 57
Depression
Beck Depression Inventory (BDI) will assess depression. The BDI is a 21 item questionnaire measuring the severity of depression. Higher scores indicate greater levels of depression.
Measured: Days 29 to 57
Polysymptomatic distress
Polysymptomatic distress will be assessed by the Fibromyalgia Symptom Score (FSS), a patient reported outcome measuring the extent of polysymptomatic distress on a scale ranging from 0-31. Higher scores correspond to greater polysymptomatic distress.
Measured: Day 29
Polysymptomatic distress
Polysymptomatic distress will be assessed by the Fibromyalgia Symptom Score (FSS), a patient reported outcome measuring the extent of polysymptomatic distress on a scale ranging from 0-31. Higher scores correspond to greater polysymptomatic distress.
Measured: Day 57
Polysymptomatic distress
Polysymptomatic distress will be assessed by the Fibromyalgia Symptom Score (FSS), a patient reported outcome measuring the extent of polysymptomatic distress on a scale ranging from 0-31. Higher scores correspond to greater polysymptomatic distress.
Measured: Days 29 to 57
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K)
SLEDAI-2K is a 24 item index which are scored by an investigator as either present or absent. Items include clinical and laboratory features of SLE. Higher scores correspond to greater disease activity.
Measured: Day 28
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K)
SLEDAI-2K is a 24 item index which are scored by an investigator as either present or absent. Items include clinical and laboratory features of SLE. Higher scores correspond to greater disease activity.
Measured: Day 57
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K)
SLEDAI-2K is a 24 item index which are scored by an investigator as either present or absent. Items include clinical and laboratory features of SLE. Higher scores correspond to greater disease activity.
Measured: Days 29 to 57
BILAG (British Isles Lupus Assessment Group) 2004
BILAG 2004 index assesses SLE disease activity in nine organ symptoms. Each domain is categorized into 1 of 5 levels (A, B, C, D, E). Lower letters (e.g. A) indicate more active disease.
Measured: Day 28
BILAG (British Isles Lupus Assessment Group) 2004
BILAG 2004 index assesses SLE disease activity in nine organ symptoms. Each domain is categorized into 1 of 5 levels (A, B, C, D, E). Lower letters (e.g. A) indicate more active disease.
Measured: Day 57
BILAG (British Isles Lupus Assessment Group) 2004
BILAG 2004 index assesses SLE disease activity in nine organ symptoms. Each domain is categorized into 1 of 5 levels (A, B, C, D, E). Lower letters (e.g. A) indicate more active disease.
Measured: Days 29 to 57
CLASI (Cutaneous LE Disease Area and Severity Index)
CLASI assesses SLE skin disease activity and damage. Higher scores indicate greater levels of cutaneous disease.
Measured: Day 28
CLASI (Cutaneous LE Disease Area and Severity Index)
CLASI assesses SLE skin disease activity and damage. Higher scores indicate greater levels of cutaneous disease.
Measured: Day 57
CLASI (Cutaneous LE Disease Area and Severity Index)
CLASI assesses SLE skin disease activity and damage. Higher scores indicate greater levels of cutaneous disease.
Measured: Days 29 to 57
Musculoskeletal disease activity--patient
Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Day 5
Musculoskeletal disease activity--patient
Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Day 29
Musculoskeletal disease activity--patient
Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Day 57
Musculoskeletal disease activity--patient
Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Days 29 to 57
Musculoskeletal disease activity--physician
Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Day 5
Musculoskeletal disease activity--physician
Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Day 28
Musculoskeletal disease activity--physician
Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Day 57
Musculoskeletal disease activity--physician
Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity.
Measured: Days 28 to 57
Morning Stiffness
Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness.
Measured: Day 5
Morning Stiffness
Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness.
Measured: Day 28
Morning Stiffness
Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness.
Measured: Day 57
Morning Stiffness
Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness.
Measured: Days 29 to 57
Patient assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the patient.
Measured: Day 5
Patient assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the patient.
Measured: Day 28
Patient assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the patient.
Measured: Day 57
Physician assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator.
Measured: Day 5
Physician assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator.
Measured: Day 28
Physician assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator.
Measured: Day 57
Lupus Low Disease Activity State (LLDAS)
LLDAS is a state achieved when there are minimal signs or symptoms of lupus disease activity while the patient is on low dose corticosteroids and stable therapy.
Measured: Day 28
Lupus Low Disease Activity State (LLDAS)
LLDAS is a state achieved when there are minimal signs or symptoms of lupus disease activity while the patient is on low dose corticosteroids and stable therapy.
Measured: Day 57
SRI-4
SRI-4 is a composite categorical response measure of improvement in SLE disease activity from a comparator timepoint/baseline. Achievement of the SRI-4 indicates a clinically meaningful response.
Measured: Day 28
SRI-4
SRI-4 is a composite categorical response measure of improvement in SLE disease activity from a comparator timepoint/baseline. Achievement of the SRI-4 indicates a clinically meaningful response.
Measured: Day 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2025
- Study start25 Jul 2025
- Primary completionFeb 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Collaborators
- Lupus Research Alliance
- Responsible party
- Sponsor
- Investigators
- Cynthia Aranow, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06987565
- Sponsor's protocol ID
- 21-0331
- Acronym
- TvSSLE
- Status last verified
- Sep 2026
- First submitted
- 23 Apr 2025
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared with researchers with a proposals directed to caranow@northwell.edu. IPD data collected during the trial, after deidentification hat underlie results in a publication will be shared and will be available by 6 months to 3 years following publication of the manuscript. gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Vagus Nerve Stimulation in SLE (TvSSLE)
- ClinicalTrials.gov ID
- NCT06987565
- Acronym / sponsor ID
- TvSSLE / 21-0331
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Systemic Lupus Erythematosus, Pain, Vagus nerve stimulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Collaborators
- Lupus Research Alliance
- Study start
- 25 Jul 2025 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 23 May 2025 (actual)
- 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.
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Joint and muscle pain and fatigue are extremely common among patients and contribute to a reduced quality of life. Available therapies may be associated with significant side effects and many patients do not achieve an adequate response to these treatments. Therefore, there is an unmet need to develop new strategies to reduce pain and fatigue. Filling this need would significantly improve patients' quality of life. This trial will evaluate the effects of a novel approach, stimulating the vagus nerve, a nerve originating in the brain as a potential therapeutic intervention for treatment of musculoskeletal pain and fatigue. Vagus nerve stimulation has multiple beneficial effects and is one of the body's own ways to modulate the immune system. One can stimulate the vagus nerve via the skin at the neck or at specific locations in the ear, (transcutaneous vagus nerve stimulation: tcVNS). We recently completed a short, small scale randomized, placebo controlled trial of tcVNS in patients with SLE and observed dramatic benefits on musculoskeletal pain and fatigue. The treatment was safe without side effects. We are therefore proposing a longer trial to validate our initial findings and to look at durability. In this study, 18 patients with musculoskeletal pain will be followed for 2 months and will receive tcVNS or placebo (sham stimulation) for 5 minutes/day for 28 days. Patients will have a 1 out of 3 chance of receiving sham stimulation and neither the patient nor the evaluating investigator will know the actual treatment. The stimulations are self-administered, are non-painful and have not been associated with serious risks. After 28 days of stimulation, treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate durability. Pain, fatigue and disease activity will be evaluated as well as possible side effects will be monitored throughout the trial. This study will also explore biologic mechanisms that may be responsible for the potential clinical effects. This will include possible effects of stimulation on gut permeability and the stool microbiome, areas that may play a significant role contributing to SLE disease and its manifestations. The development of an effective treatment without significant side effects would be extremely valuable and a significant advance for patients with SLE. If efficacious, tcVNS offers a non-toxic, non-immunosuppressive strategy to control two of the most common symptoms of this disease.
Detailed description
Musculoskeletal (MS) pain and fatigue are common symptoms of patients with Systemic Lupus Erythematosus (SLE) affecting up to 95% and contributing to a reduced quality of life. Safe and efficacious treatment remains an unmet need for these disease manifestations. Stimulation of the vagus nerve results in beneficial effects in patients. We recently completed a short , small scale, randomized, sham-controlled, double blind clinical trial of transcutaneous vagus nerve stimulation (taVNS) in patients with SLE. The clinical benefit on MS pain and fatigue was dramatic. We now propose a randomized sham controlled clinical trial assessing the efficacy and durability of a longer exposure to taVNS (28 days in comparison to the 4 day exposure in the previous trial) in 18 patients randomized 2: 1 with musculoskeletal pain. After 28 days of stimulation, the treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate the treatment's durability. Pain, fatigue, disease activity (global and musculoskeletal) and safety will be evaluated and safety will be monitored throughout the trial. In this clinical trial we will also explore potential biologic mechanisms and pathways by which taVNS exerts ifs effects in SLE, including potential effects on gut permeability and the microbiome.
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 |
|---|---|---|
| Vagus Nerve Stimulation | Active comparator | Device: Active vagus nerve stimulationPatients will receive transcutaneous stimulation of the left vagus nerve for 5 minutes daily for 28 consecutive days. |
| Sham Vagus Nerve Stimulation | Placebo comparator | Device: Sham vagus nerve stimulationPatients will receive sham transcutaneous stimulation of the of the left vagus nerve for 5 minutes daily for 28 consecutive days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- SLE (defined by the ACR or SLICC criteria),
- Musculoskeletal pain ≥ 4 on a non-anchored VAS 10 cm scale,
- BILAG C or greater on the Musculoskeletal Domain of the BILAG 2004,
- If on corticosteroids, the dose must be stable and ≤ 10 mg/day (prednisone or equivalent) for at least 14 days before baseline,
- If on background immunosuppressive treatment the dose must be stable for at least 28 days before baseline,
Key exclusion criteria (23 listed)
- Initiation of immunosuppressive or antimalarial treatment within 3 months of baseline,
- Treatment with cyclophosphamide within 2 months of baseline,
- Initiation of anifrolumab within 3 months of baseline
- Initiation of belimumab within 6 months of baseline,
- Expectation to increase steroids and/or immunosuppressive treatment,
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 |
|---|---|---|
| Active vagus nerve stimulationPatients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated. Patients will be followed through day 57 to assess durability of the intervention. | Device | Vagus Nerve Stimulation |
| Sham vagus nerve stimulationPatients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated, however, the vagus nerve will not be stimulated. Patients will be followed through day 57 to assess durability of the intervention. | Device | Sham Vagus Nerve Stimulation |
Primary outcome
Change in Musculoskeletal Pain From Baseline.
Time frame: 28 days
Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain.
75 secondary outcomes
Percentage of Subjects With Treatment Emergent Adverse Events.
Time frame: 57 days
Change in Musculoskeletal Pain From Baseline
Time frame: 5 days
Change in Musculoskeletal Pain From Baseline
Time frame: 57 days
Change in Musculoskeletal Pain From Day 29 to Day 57
Time frame: day 29 to day 57
Fatigue
Time frame: 5 days
Fatigue
Time frame: 28 days
Fatigue
Time frame: 57 days
Fatigue
Time frame: day 29 to day 57
Tender Joint Reduction
Time frame: 5 days
Tender Joint Reduction
Time frame: 28 days
Tender Joint Reduction
Time frame: 57 days
Tender Joint Reduction
Time frame: Day 29 to Day 57
Swollen joint reduction
Time frame: 5 days
Swollen joint reduction
Time frame: 28 days
Swollen joint reduction
Time frame: 57 days
Swollen joint reduction
Time frame: Day 29 to Day 57
Physician Global Assessment of Disease Activity (PGA)
Time frame: Day 5
Physician Global Assessment of Disease Activity (PGA)
Time frame: Day 28
Physician Global Assessment of Disease Activity (PGA)
Time frame: Day 57
Physician Global Assessment of Disease Activity (PGA)
Time frame: Days 29 to 57
Patient Global Assessment of Disease (PtGA)
Time frame: Day 5
Patient Global Assessment of Disease (PtGA)
Time frame: Day 28
Patient Global Assessment of Disease (PtGA)
Time frame: Day 57
Patient Global Assessment of Disease (PtGA)
Time frame: Days 29 to 57
Pain intensity
Time frame: 5 days
Pain intensity
Time frame: 28 days
Pain intensity
Time frame: 57 days
Pain intensity
Time frame: Days 29 to 57
Pain interference
Time frame: 5 days
Pain interference
Time frame: 28 days
Pain interference
Time frame: 57 days
Pain interference
Time frame: Days 29 to 57
Health Related Quality of Life (HRQoL))
Time frame: 28 days
Health Related Quality of Life (HRQoL))
Time frame: Day 57
Health Related Quality of Life (HRQoL))
Time frame: Days 29 to 57
Anxiety
Time frame: Day 29
Anxiety
Time frame: Day 57
Anxiety
Time frame: Days 29 to 57
Depression
Time frame: Day 28
Depression
Time frame: Day 57
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Individual participant dataSharing planned: Yes. IPD will be shared with researchers with a proposals directed to caranow@northwell.edu. IPD data collected during the trial, after deidentification hat underlie results in a publication will be shared and will be available by 6 months to 3 years following publication of the manuscript. gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website
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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.
Cynthia Aranow, MD principal investigator
Northwell Health
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 Active vagus nerve stimulation in people with Systemic Lupus Erythematosus, run by Northwell Health 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 7 inclusion and 23 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: looking for participants now, as of the sponsor's last update on 17 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sanita Kandasami (516 562-2401, skandasami@northwell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Musculoskeletal Pain From Baseline. (time frame: 28 days). 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 17 Sep 2026.