Near InfraRed Fluorescence Imaging of Lymphatic Transport Using Indocyanine Green: Phase II Pilot
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Clearance
研究概览
简要总结
Lymphatic transport was previously examined by these investigators using Near InfraRed Indocyanine Green fluorescence imaging (NIR-ICG) of the upper extremities. They established reliable and reproducible methodologies in RA patients. The purpose of this phase 2 pilot is to study RA disease progression and effectiveness as well as the mechanism of action of clinical interventions using established NIR-ICG methodologies in previous studies.
详细描述
In preclinical studies, these investigators demonstrated that amelioration of tumor necrosis factor (TNF)-induced arthritis with anti-TNF, but not methotrexate (MTX) therapy, correlates with normalization of ICG clearance and popliteal lymph node (PLN) contractions. In RA patients during hand flare, it was found that ICG clearance from the web spaces, and numbers of ICG+ lymphatic basilic vessels of RA hands, are significantly decreased vs. healthy controls. Based on these observations, two important questions warrant testing to assess the clinical utility of NIR-ICG biomarkers in RA hands: Does amelioration of active synovitis pre and post treatment) correlate with: 1) increased ICG clearance (primary outcome) and/or 2) recovery of basilic ICG+ vessels (secondary outcome)? To formally address these questions, a clinical pilot will be conducted of early RA patients with symptomatic disease in their hand(s), who will undergo NIR-ICG imaging at baseline, 16-weeks, and 1-year post anti-TNF therapy, and examine if NIR-ICG outcome measures predict and correlate with clinical response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
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
- •Ability to provide written informed consent
- •Subjects must be 18 years old or older
- •RA subjects must fulfill 2010 American College of Rheumatology (ACR) criteria with a DAS28-C-Reactive Protein (CRP) >3.5
- •Must have 1 year or less of disease
- •Must be MTX inadequate responder (DAS28-CRP >2.6 at 4 months of therapy) OR experience a flare on MTX (self-reported and score of >25 on the Outcome Measures in Rheumatology (OMERACT) Flare questionnaire AND are starting an anti-TNF therapy.
- •Must have active synovitis in one or both hands confirmed by ultrasound
- •Established RA
- •Ability to provide written informed consent
- •Subjects must be 18 years of age or older
- •RA subjects must fulfill 2010 ACR criteria with a DAS-CRP >3.5
- •Must have at least 10 years of disease
- •Must have active synovitis in one or both hands confirmed by ultrasound
- •Must be on a stable dose of DMARD (MTX, leflunomide, azulfidine, hydroxychloroquine), Janus Kinase (JAK) inhibitor or biologic agent for 8 weeks
排除标准
- •All PATIENTS
- •Active systemic disorders or inflammatory conditions other than RA, (i.e., chronic infections with hepatitis B, hepatitis C or HIV) that would confound the study results.
- •Known sensitivity to iodine because of residual iodide in Indocyanine Green
- •Pregnant women should not participate; pregnancy tests will not be performed
- •Inability to donate blood due to poor venous access
研究组 & 干预措施
Established RA (> 10 years of disease)
Patients with symptomatic established RA (>10 years) will be invited to participate in an ICG injections followed by NIR-ICG imaging and NIR-ICG imaging visit 1 week later. Total length of participation will be up to 1 week (+3 days)
干预措施: MultiSpectral Imaging System (Device)
Established RA (> 10 years of disease)
Patients with symptomatic established RA (>10 years) will be invited to participate in an ICG injections followed by NIR-ICG imaging and NIR-ICG imaging visit 1 week later. Total length of participation will be up to 1 week (+3 days)
干预措施: Indocyanine green (Drug)
Early RA (<1 year of disease)
In this single center study, early RA subjects (<1 year of disease) who are MTX inadequate responders or experience a flare (see inclusion criteria for detail) on MTX and are starting an anti-TNF therapy will be invited to participate to receive ICG injections at Baseline (prior to the start of medication), week 16 and week 52. NIR-ICG imaging will be done immediately post injection and 1 week later for a total of three injection/imaging visits and three imaging visits without injections. See schedule of events for more detail. Total length of participation will be up to 53 weeks (+3days).
干预措施: Indocyanine green (Drug)
Early RA (<1 year of disease)
In this single center study, early RA subjects (<1 year of disease) who are MTX inadequate responders or experience a flare (see inclusion criteria for detail) on MTX and are starting an anti-TNF therapy will be invited to participate to receive ICG injections at Baseline (prior to the start of medication), week 16 and week 52. NIR-ICG imaging will be done immediately post injection and 1 week later for a total of three injection/imaging visits and three imaging visits without injections. See schedule of events for more detail. Total length of participation will be up to 53 weeks (+3days).
干预措施: MultiSpectral Imaging System (Device)
结局指标
主要结局
Clearance
时间窗: 1 week post injection
The change in Indocyanine Green signal intensity (arbitrary units) over time is measured by observing the fluorescence using the Multispectral Imaging System. The MSImager software analyses the signal intensity. This outcome measure will be quantified for both early RA and late RA subjects.
次要结局
- Lymphatic Vessels(16 weeks)
- Contraction Rate(16 weeks)
研究者
Christopher Ritchlin
Professor
University of Rochester