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Completed

NCT Number: NCT02822989

Using the Cholinergic Anti-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune, inflammatory disease and musculoskeletal pain is one of the most common symptoms. This study will investigate whether transcutaneous stimulation of the vagus nerve will decrease lupus musculoskeletal pain. This study will additionally investigate the biologic effects of vagus nerve stimulation on inflammation. It will be the first clinical study using one of the body's own pathways of modulating the immune system and inflammatory response, the cholinergic anti-inflammatory pathway, in SLE.

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Key information

Conditions

Lupus Erythematosus, Systemic Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Inflammation Muscular Diseases Musculoskeletal Diseases Musculoskeletal Pain Neurologic Manifestations Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Feinstein Institute

Manhasset, New York, 11030, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥18 years,
  • SLE (defined by the ACR or SLICC criteria),
  • Musculoskeletal pain ≥ 4 on a non-anchored VAS 10 cm scale
  • BILAG C on Musculoskeletal Domain of the BILAG 2004
  • If on corticosteroids, the dose must be stable and ≤ 10mg/day (prednisone or equivalent) for at least 28 days before baseline,
  • If on background immunosuppressive treatment the dose must be stable for at least 28 days before baseline
  • Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion criteria

  • Treatment with rituximab within one year of baseline (subjects with previous treatment with rituximab can enter study only with documentation of B cell repletion),
  • Treatment with cyclophosphamide within 2 months of baseline,
  • Expectation to increase steroids and/or immunosuppressive treatment,
  • Anti-phospholipid syndrome,
  • Fibromyalgia (fibromyalgia will be defined as a score > 13 on the Fibromyalgia Symptom Scale (FSS).
  • Treatment with an anti-cholinergic medication, including over the counter medications,
  • Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
  • Current tobacco or nicotine user,
  • 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,
  • Comorbid disease that may require administration of corticosteroid use,
  • Inability to comply with study and follow-up procedures.

Treatment and study plan

vagus nerve stimulation

Device

Patients will receive transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes daily for 4 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes to be placed at the ear for stimulation. The specific target at the ear will be the auricular branch of the vagus nerve which innervates the skin of the ear canal. Electrodes will be placed near/at the entrance to the canal of the ear to provide stimulation to the auricular branch.

Sham vagus nerve stimulation

Device

Patients will receive sham transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes daily for 4 consecutive days. Sham stimulation will be performed in the identical manner as true transcutaneous stimulation except that the patient will not receive electrical stimulation of the vagus nerve.

Primary outcomes

  1. Change in Musculoskeletal Pain From Baseline.

    Time frame: 5 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.

  2. Percentage of Subjects With Treatment Emergent Adverse Events.

    Time frame: 12 days

    The percentage of participants with grade 2 or higher treatment emergent adverse events will be assessed using the NCI-CTAEversion4.

Secondary outcomes

  1. Change in Musculoskeletal Pain From Baseline

    Time frame: 12 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.

  2. Fatigue

    Time frame: 5 days

    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.

  3. Fatigue

    Time frame: 12 days

    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.

  4. Tender Joint Reduction

    Time frame: 5 days

    The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.

  5. Tender Joint Reduction

    Time frame: 12 days

    The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.

  6. Swollen Joint Count Reduction

    Time frame: 5 days

    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.

  7. Swollen Joint Count Reduction

    Time frame: 12 days

    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.

  8. Physician Global Assessment of Disease Activity (PGA)

    Time frame: 5 days

    Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.

  9. Physician Global Assessment of Disease Activity (PGA)

    Time frame: 12 days

    Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.

  10. Patient Global Assessment of Disease (PtGA)

    Time frame: 5 days

    Change in Patient Global Assessment of disease (PtGA) from baseline. This measure is a 10 cm visual analog scale (0-10); higher scores indicate a higher patient assessment of their disease activity.

  11. Patient Global Assessment of Disease (PtGA)

    Time frame: 12 days

    Change in Patient Global Assessment of disease (PtGA) from baseline. This measure is a 10 cm visual analog scale (0-10); higher scores indicate a higher patient assessment of their disease activity.

Other outcomes

  1. CRP

    Time frame: 5 days

    Change from baseline of CRP levels in patient serum.

  2. CRP

    Time frame: 12 days

    Change from baseline of CRP levels in patient serum.

  3. IFNα

    Time frame: 5 days

    Change from baseline of IFNα levels an inflammatory cytokine in patient serum.

  4. IFNα

    Time frame: 12 days

    Change from baseline of IFNα levels an inflammatory cytokine in patient serum.

  5. Il-6

    Time frame: 5 days

    Change from baseline of Il-6 levels in patient sera

  6. Il-6

    Time frame: 12 days

    Change from baseline of Il-6 levels in patient sera.

  7. IL-1β

    Time frame: 5 days

    Change from baseline of levels of IL-1β, an inflammatory cytokine in patient serum.

  8. IL-1β

    Time frame: 12 days

    Change from baseline of levels of IL-1β, an inflammatory cytokine in patient serum.

  9. TNF

    Time frame: 5 days

    Change from baseline of TNF levels, an inflammatory cytokine in patient serum.

  10. TNF

    Time frame: 12 days

    Change from baseline of TNF levels, an inflammatory cytokine in patient serum.

  11. IL-10

    Time frame: 5 days

    Change from baseline of IL-10 levels in patient serum.

  12. IL-10

    Time frame: 12 days

    Change from baseline of IL-10 levels in patient serum.

  13. IL1-RA

    Time frame: 5 days

    Change from baseline of Il-1 RA levels in patient sera.

  14. IL-1 RA

    Time frame: 12 days

    Change from baseline of Il-1 RA levels in patient sera.

  15. Il-18

    Time frame: 5 days

    Change from baseline of Il-18 levels in patient sera.

  16. Il-18

    Time frame: 12 days

    Change from baseline of Il-18 levels in patient sera.

  17. IL-8

    Time frame: 5 days

    Change from baseline of serum levels of IL-8

  18. IL-8

    Time frame: 12 days

    Change from baseline of serum levels of IL-8

  19. Substance P

    Time frame: 5 days

    Change from baseline of plasma levels of substance P.

  20. Substance P

    Time frame: 12 days

    Change from baseline of plasma levels of substance P.

  21. Neuropeptide Y

    Time frame: 12 days

    Change from baseline of plasma levels of Neuropeptide Y.

  22. Neuropeptide Y

    Time frame: 5 days

    Change from baseline of plasma levels of Neuropeptide Y.

  23. Calcitonin Gene-Related Peptide (CGRP)

    Time frame: 5 days

    Change from baseline of plasma levels of CGRP.

  24. Calcitonin Gene-Related Peptide (CGRP)

    Time frame: 12 days

    Change from baseline of plasma levels of CGRP.

  25. Kynurenine

    Time frame: 5 days

    Change from baseline of serum levels of kynurenine

  26. Kynurenine

    Time frame: 12 days

    Change from baseline of serum levels of kynurenine

  27. Quinolinic Acid

    Time frame: 5 days

    Change from baseline of serum levels of quinolinic acid

  28. Quinolinic Acid

    Time frame: 12 days

    Change from baseline of serum levels of quinolinic acid

  29. Kynurenine/Tryptophan

    Time frame: 5 days

    Change from baseline of serum Kynurenine/Tryptophan

  30. Kynurenine/Tryptophan

    Time frame: 12 days

    Change from baseline of serum Kynurenine/Tryptophan

Sponsors and collaborators

Lead sponsor

Northwell Health

Other

Collaborators

  • John and Marcia Goldman Foundation

Registry information

Official study title

Using the Cholinergic Anit-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain

Important dates

Study start
2017
Primary completion
2018
Study completion
2020
First posted
Jul 6, 2016
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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