Transcutaneous Vagus Nerve Stimulation in SLE (TvSSLE)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Change in Musculoskeletal Pain From Baseline.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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,
- •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.
研究组 & 干预措施
Vagus Nerve Stimulation
Patients will receive transcutaneous stimulation of the left vagus nerve for 5 minutes daily for 28 consecutive days.
干预措施: Active vagus nerve stimulation (Device)
Sham Vagus Nerve Stimulation
Patients will receive sham transcutaneous stimulation of the of the left vagus nerve for 5 minutes daily for 28 consecutive days.
干预措施: Sham vagus nerve stimulation (Device)
结局指标
主要结局
Change in Musculoskeletal Pain From Baseline.
时间窗: 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.
次要结局
- Swollen joint reduction(Day 29 to Day 57)
- Patient Global Assessment of Disease (PtGA)(Days 29 to 57)
- Pain intensity(Days 29 to 57)
- Pain interference(Days 29 to 57)
- Change in Musculoskeletal Pain From Day 29 to Day 57(day 29 to day 57)
- Fatigue(day 29 to day 57)
- Tender Joint Reduction(Day 29 to Day 57)
- Physician Global Assessment of Disease Activity (PGA)(Days 29 to 57)
- Physician assessment of response(Day 57)
- Lupus Low Disease Activity State (LLDAS)(Day 57)
- SRI-4(Day 57)
- Health Related Quality of Life (HRQoL))(Days 29 to 57)
- Anxiety(Days 29 to 57)
- Depression(Days 29 to 57)
- Polysymptomatic distress(Days 29 to 57)
- Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K)(Days 29 to 57)
- BILAG (British Isles Lupus Assessment Group) 2004(Days 29 to 57)
- CLASI (Cutaneous LE Disease Area and Severity Index)(Days 29 to 57)
- Musculoskeletal disease activity--patient(Days 29 to 57)
- Musculoskeletal disease activity--physician(Days 28 to 57)
- Morning Stiffness(Days 29 to 57)
- Patient assessment of response(Day 57)
- Percentage of Subjects With Treatment Emergent Adverse Events.(57 days)
- Change in Musculoskeletal Pain From Baseline(57 days)