Analysis of Lymphatic Fluid From the Thoracic Duct of Healthy People and People With Multiple Sclerosis (MS) Before and After Ofatumumab Treatment
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- B Cells
研究概览
简要总结
In this study, lymph fluid will be collected by cannulation of the thoracic duct, a minimally invasive procedure performed by interventional radiologists. Single time point and serial collection through an indwelling cannula will allow for comparisons between immune cells in the periphery and deep lymphatic system in MS and healthy controls and in MS, changes in responses to a FDA approved therapy ofatumumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants eligible for inclusion in this study must meet all of the following criteria:
- •Written informed consent must be obtained before any assessment is performed.
- •Adult participants aged 18 to 40 years (inclusive) at Screening.
- •Participants must be able to understand English and be able to review and comprehend the informed consent form independently or with the help of research staff
- •No use of systemic glucocorticoids in the past 4 weeks
- •For participants with MS following additional criteria need to be met:
- •Diagnosis of MS according to the 2017 Revised McDonald criteria.
- •Ability to undergo several MRIs
- •Disability status at Screening with an EDSS score of 0 to 4 (inclusive)
- •MS treatment history restricted to Interferons and/glatiramer acetate treatment only or untreated to date
- •Neurologically stable within one month prior to interventional procedure.
排除标准
- •1. Participants suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator.
- •2. Participants with primary progressive MS (Polman C et al., 2011)
- •Participants meeting criteria for neuromyelitis optica (Wingerchuck D et al., 2015)
- •Participants with disease duration of more than 10 years
- •Participants who are pregnant or nursing (lactating)
- •Participants with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency)
- •Participants with active systemic bacterial, viral or fungal infections, or known to have acquired immunodeficiency syndrome (AIDS)
- •Participants with neurological symptoms consistent with PML or confirmed PML
- •Participants at risk of developing or having reactivation of syphilis or tuberculosis
- •History of cardiovascular disease or uncontrolled hypertension
- •History of diabetes mellitus
- •History of cancer (other than localized skin cancer) in the previous 5 years
- •Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to first study drug administration
- •Immunization with non-live vaccines within 2 weeks of the study procedure
- •Participants at risk of developing or having reactivation of hepatitis: Positive results at Screening for serological markers for hepatitis (H) B and C indicating acute or chronic infection:
- •HBs Ag and/or anti-HBc IgM and/or HB virus deoxyribonucleic acid (DNA)
- •anti-HBs negative and Anti-HBc positive
- •anti-HC IgG (if positive IgG, HCV-RNA PCR will be performed and if negative, participant can be enrolled)
- •Use of other investigational drugs at the time of enrollment (Screening) or within the prior 30 days, or five elimination half-lives, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
- •Absolute neutrophil count (ANC) <750/mm3;
- •Hemoglobin <10.0 g/dL
- •Platelet count <100,000/mm3
- •Prothrombin time (PT) or international normalized ration (INR) >1.5 x ULN
研究组 & 干预措施
'In-and-out' catheterization
Safety and immune-cell profile of lymphatic fluid in MS patients with a single time-point sampling of lymphatic fluids and peripheral blood compared to healthy controls.
Two healthy controls and six patients with early MS (never treated or at least 90 days after discontinued treatment with glatiramer acetate or interferons), who consent to the 'In-and-out' catheter procedure. MS participants can also consent to OMB treatment with 2-year follow-up.
干预措施: thoracic duct cannulation (Procedure)
"Indwelling" catheterization
immune-biology in people with MS before and during/after OMB treatment within thoracic duct and peripheral blood via indwelling catheter and multiple time-point sampling compared to healthy controls (without drug treatment).
Twelve patients with early MS (never treated or at least 90 days after discontinued treatment with glatiramer acetate or interferons), who consent to treatment with OMB and to the indwelling catheter procedure with serial sampling and up to four healthy controls (no drug treatment)
干预措施: thoracic duct cannulation (Procedure)
结局指标
主要结局
B Cells
时间窗: up to 21 days
Change in proportion of flow cytometry defined naïve (CD27-) and memory (CD27+) B cells in thoracic duct of patients with MS prior to and following anti-CD20 therapy with Ofatumumab
Safety and Tolerability
时间窗: up to 21 days
Quantified as percent of the study population experiencing serious adverse event from in-and-out catherization procedure and from "indwelling" catheterization procedure
次要结局
- Immune cell profiles (MS and healthy controls)(up to 21 days)
- Immune cell profiles (ofatumumab)(up to 21 days)