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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
18
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.
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.
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.
Time frame: 28 days
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 5 days
Tender Joint Reduction
The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.
Time frame: 28 days
Tender Joint Reduction
The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Days 29 to 57
Patient assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the patient.
Time frame: Day 5
Patient assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the patient.
Time frame: Day 28
Patient assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the patient.
Time frame: Day 57
Physician assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator.
Time frame: Day 5
Physician assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator.
Time frame: Day 28
Physician assessment of response
Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 57
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.