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

June 10, 2026 updated by: Cynthia Aranow, MD, Northwell Health

Using the Cholinergic Anit-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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
19

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Manhasset, New York, United States, 11030
        • Feinstein Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Treatment with rituximab within one year of baseline (subjects with previous treatment with rituximab can enter study only with documentation of B cell repletion),
  2. Treatment with cyclophosphamide within 2 months of baseline,
  3. Expectation to increase steroids and/or immunosuppressive treatment,
  4. Anti-phospholipid syndrome,
  5. Fibromyalgia (fibromyalgia will be defined as a score > 13 on the Fibromyalgia Symptom Scale (FSS).
  6. Treatment with an anti-cholinergic medication, including over the counter medications,
  7. Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
  8. Current tobacco or nicotine user,
  9. Joint replacement within 60 days prior to study enrollment or planned within the course of the study,
  10. Any planned surgical procedure requiring general anesthesia within the course of the study,
  11. Intra-articular cortisone injections within 28 days of the start of study,
  12. Chronic inflammatory disorders apart from SLE affecting the joints,
  13. 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,
  14. Active infection including hepatitis B or hepatitis C at baseline,
  15. Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention,
  16. Pregnancy or lactation,
  17. Comorbid disease that may require administration of corticosteroid use,
  18. Inability to comply with study and follow-up procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Vagus Nerve Stimulation
Subjects randomized to this arm will receive transcutaneous vagus nerve stimulation for 5 minutes on 4 consecutive days.
Device: Vagus nerve stimulation
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 Comparator: Sham Vagus Nerve Stimulation
Subjects randomized to this arm will receive sham stimulation for 5 minutes for 4 consecutive days.
Device: Sham vagus nerve stimulation
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
5 days
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.
12 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
5 days
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 days
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.
12 days
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.
12 days
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.
12 days
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.
5 days
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.
12 days
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.
5 days
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.
12 days
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.
5 days
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.
12 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
CRP
Time Frame: 5 days
Change from baseline of CRP levels in patient serum.
5 days
CRP
Time Frame: 12 days
Change from baseline of CRP levels in patient serum.
12 days
IFNα
Time Frame: 5 days
Change from baseline of IFNα levels an inflammatory cytokine in patient serum.
5 days
IFNα
Time Frame: 12 days
Change from baseline of IFNα levels an inflammatory cytokine in patient serum.
12 days
Il-6
Time Frame: 5 days
Change from baseline of Il-6 levels in patient sera
5 days
Il-6
Time Frame: 12 days
Change from baseline of Il-6 levels in patient sera.
12 days
IL-1β
Time Frame: 5 days
Change from baseline of levels of IL-1β, an inflammatory cytokine in patient serum.
5 days
IL-1β
Time Frame: 12 days
Change from baseline of levels of IL-1β, an inflammatory cytokine in patient serum.
12 days
TNF
Time Frame: 5 days
Change from baseline of TNF levels, an inflammatory cytokine in patient serum.
5 days
TNF
Time Frame: 12 days
Change from baseline of TNF levels, an inflammatory cytokine in patient serum.
12 days
IL-10
Time Frame: 5 days
Change from baseline of IL-10 levels in patient serum.
5 days
IL-10
Time Frame: 12 days
Change from baseline of IL-10 levels in patient serum.
12 days
IL1-RA
Time Frame: 5 days
Change from baseline of Il-1 RA levels in patient sera.
5 days
IL-1 RA
Time Frame: 12 days
Change from baseline of Il-1 RA levels in patient sera.
12 days
Il-18
Time Frame: 5 days
Change from baseline of Il-18 levels in patient sera.
5 days
Il-18
Time Frame: 12 days
Change from baseline of Il-18 levels in patient sera.
12 days
IL-8
Time Frame: 5 days
Change from baseline of serum levels of IL-8
5 days
IL-8
Time Frame: 12 days
Change from baseline of serum levels of IL-8
12 days
Substance P
Time Frame: 5 days
Change from baseline of plasma levels of substance P.
5 days
Substance P
Time Frame: 12 days
Change from baseline of plasma levels of substance P.
12 days
Neuropeptide Y
Time Frame: 12 days
Change from baseline of plasma levels of Neuropeptide Y.
12 days
Neuropeptide Y
Time Frame: 5 days
Change from baseline of plasma levels of Neuropeptide Y.
5 days
Calcitonin Gene-Related Peptide (CGRP)
Time Frame: 5 days
Change from baseline of plasma levels of CGRP.
5 days
Calcitonin Gene-Related Peptide (CGRP)
Time Frame: 12 days
Change from baseline of plasma levels of CGRP.
12 days
Kynurenine
Time Frame: 5 days
Change from baseline of serum levels of kynurenine
5 days
Kynurenine
Time Frame: 12 days
Change from baseline of serum levels of kynurenine
12 days
Quinolinic Acid
Time Frame: 5 days
Change from baseline of serum levels of quinolinic acid
5 days
Quinolinic Acid
Time Frame: 12 days
Change from baseline of serum levels of quinolinic acid
12 days
Kynurenine/Tryptophan
Time Frame: 5 days
Change from baseline of serum Kynurenine/Tryptophan
5 days
Kynurenine/Tryptophan
Time Frame: 12 days
Change from baseline of serum Kynurenine/Tryptophan
12 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Northwell Health

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
John and Marcia Goldman Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cynthia Aranow, M.D., Northwell Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 26, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 5, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 6, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 8, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HS16-0171

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings