Back to resultsUsing the Cholinergic Anti-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain
Primary Purpose
Lupus Erythematosus, Systemic, Musculoskeletal Pain
Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vagus nerve stimulation
Sham vagus nerve stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring Lupus Erythematosus, Systemic, Musculoskeletal Pain, Inflammation
Eligibility Criteria
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.
Sites / Locations
- Feinstein Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Vagus Nerve Stimulation
Sham Vagus Nerve Stimulation
Arm Description
Subjects randomized to this arm will receive transcutaneous vagus nerve stimulation for 5 minutes on 4 consecutive days.
Subjects randomized to this arm will receive sham stimulation for 5 minutes for 4 consecutive days.
Outcomes
Primary Outcome Measures
Musculoskeletal pain.
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.
Secondary Outcome Measures
SLE Disease activity
SLE disease activity will be assessed using the SLEDAI, a validated disease activity instrument for SLE.
Fatigue
Fatigue will be measured using the FACET F questionnaire which will be completed by each subject.
Fatigue
Fatigue will be measured using the FACET F questionnaire which will be completed by each subject.
Tender and swollen joint counts
The number of tender and swollen joints of the subject will be assessed by the investigator who will examine 68 potential tender joints and 66 potential swollen joints.
Tender and swollen joint counts
The number of tender and swollen joints of the subject will be assessed by the investigator who will examine 68 potential tender joints and 66 potential swollen joints.
SLE cutaneous activity
Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease.
SLE cutaneous activity
Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease.
Musculoskeletal Pain
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.
Percentage of subjects with treatment emergent adverse events.
The percentage of participants with treatment emergent adverse events will be assessed using the NCI-CTAEversion4.
Full Information
NCT ID
NCT02822989
First Posted
May 26, 2016
Last Updated
September 8, 2020
Sponsor
Northwell Health
Collaborators
John and Marcia Goldman Foundation
1. Study Identification
Unique Protocol Identification Number
NCT02822989
Brief Title
Using the Cholinergic Anti-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain
Official Title
Using the Cholinergic Anit-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
April 30, 2018 (Actual)
Study Completion Date
November 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwell Health
Collaborators
John and Marcia Goldman Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic, Musculoskeletal Pain
Keywords
Lupus Erythematosus, Systemic, Musculoskeletal Pain, Inflammation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
Randomized
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vagus Nerve Stimulation
Arm Type
Active Comparator
Arm Description
Subjects randomized to this arm will receive transcutaneous vagus nerve stimulation for 5 minutes on 4 consecutive days.
Arm Title
Sham Vagus Nerve Stimulation
Arm Type
Sham Comparator
Arm Description
Subjects randomized to this arm will receive sham stimulation for 5 minutes for 4 consecutive days.
Intervention Type
Device
Intervention Name(s)
Vagus nerve stimulation
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham vagus nerve stimulation
Intervention Description
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 Outcome Measure Information:
Title
Musculoskeletal pain.
Description
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.
Time Frame
5 days
Secondary Outcome Measure Information:
Title
SLE Disease activity
Description
SLE disease activity will be assessed using the SLEDAI, a validated disease activity instrument for SLE.
Time Frame
5 days
Title
Fatigue
Description
Fatigue will be measured using the FACET F questionnaire which will be completed by each subject.
Time Frame
5 days
Title
Fatigue
Description
Fatigue will be measured using the FACET F questionnaire which will be completed by each subject.
Time Frame
12 days
Title
Tender and swollen joint counts
Description
The number of tender and swollen joints of the subject will be assessed by the investigator who will examine 68 potential tender joints and 66 potential swollen joints.
Time Frame
5 days
Title
Tender and swollen joint counts
Description
The number of tender and swollen joints of the subject will be assessed by the investigator who will examine 68 potential tender joints and 66 potential swollen joints.
Time Frame
12 days
Title
SLE cutaneous activity
Description
Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease.
Time Frame
5 days
Title
SLE cutaneous activity
Description
Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease.
Time Frame
12 days
Title
Musculoskeletal Pain
Description
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.
Time Frame
12 days
Title
Percentage of subjects with treatment emergent adverse events.
Description
The percentage of participants with treatment emergent adverse events will be assessed using the NCI-CTAEversion4.
Time Frame
12 days
Other Pre-specified Outcome Measures:
Title
TNF, HMGB1, IL-6, Il1B, IFNα and IL10 levels
Description
Levels of inflammatory cytokines (ie TNF, HMGB1, IL-6, Il1B, IFNα and IL10) will be measured in patients sera.
Time Frame
5 days
Title
TNF, HMGB1, IL-6, Il1B, IFNα and IL10 levels
Description
Levels of inflammatory cytokines (ie TNF, HMGB1, IL-6, Il1B, IFNα and IL10) will be measured in patients sera.
Time Frame
12 days
Title
Lipopolysaccharide stimulated levels of TNF, HMGB1, IL-6, Il1B, IFNα and IL10 in whole blood.
Description
Whole blood will be taken from patients and stimulated by lipopolysaccharide. Levels of TNF, HMGB1, IL-6, Il1B, IFNα and IL10 that are produced by the cells in the whole blood will be measured.
Time Frame
5 days
Title
Lipopolysaccharide stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
Description
Whole blood will be taken from patients and stimulated by lipopolysaccharide. Levels of TNF, HMGB1, IL-6, Il1B, IFNα and IL10 that are produced by the cells in the whole blood will be measured.
Time Frame
12 days
Title
Gardiquimod stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
Description
Whole blood will be taken from patients and stimulated by gardiquimod.. Levels of TNF, HMGB1, IL-6, Il1B, IFNα and IL10 that are produced by the cells in the whole blood will be measured.
Time Frame
5 days
Title
Gardiquimod stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
Description
Whole blood will be taken from patients and stimulated by gardiquimod.. Levels of TNF, HMGB1, IL-6, Il1B, IFNα and IL10 that are produced by the cells in the whole blood will be measured.
Time Frame
12 days
Title
CpG stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
Description
Whole blood will be taken from patients and stimulated by CpG. Levels of TNF, HMGB1, IL-6, Il1B, IFNα and IL10 that are produced by the cells in the whole blood will be measured.
Time Frame
5 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia Aranow, M.D.
Organizational Affiliation
Northwell Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Feinstein Institute
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33687069
Citation
Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
Results Reference
derived
Learn more about this trial
Using the Cholinergic Anti-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain
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