Investigation of the Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still's Disease and Related Inflammatory Conditions
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- Genetic sequencing of patients
研究概览
简要总结
Background:
Inflammatory conditions can cause symptoms like fevers, arthritis, and rash. Systemic juvenile idiopathic arthritis (sJIA) is one of these conditions. So is adult-onset Still s disease (AOSD). Their causes are unknown. Researchers want to learn more about these conditions. This includes genetic changes and environmental factors.
Objective:
To study sJIA and AOSD in children and adults over time.
Eligibility:
People with known or suspected sJIA, AOSD, or similar inflammatory condition
Design:
Participants will be screened with a phone call.
Participants will have 1 visit. It may be outpatient or they may be admitted to the clinic. The visit may last up to 5 days. Participants will have:
- Medical history
- Physical exam
- Musculoskeletal exam
- Questions about overall health and quality of life, disease activity, functional status, and cognitive ability.
Participants may also have:
- Pictures taken of their skin, joints, or spine
- Blood, urine, and stool tests
- Scans or X-rays of joints with arthritis
- Chest X-ray
- Heart tests
- Skin biopsy. The skin will be numbed. The top layers of a small area will be scraped off.
Participants who have a joint aspiration may provide a fluid sample. The joint will be prepared, then fluid is removed by needle. A corticosteroid may be injected.
Participants who have a bone marrow biopsy may provide sample cells.
Participants may be seen by NIH specialists.
Members of the participant s family and healthy volunteers may give blood or saliva samples for genetic testing.
Participants may repeat some study tests every 6 months.
详细描述
Study Description:
The purpose of this protocol is to study the natural history, genetics and pathophysiology of systemic juvenile idiopathic arthritis (sJIA), adult-onset Still s disease (AOSD) and related inflammatory conditions. One of seven subtypes of juvenile idiopathic arthritis (JIA), sJIA contributes disproportionately to the morbidity and mortality of JIA and is considered by many to be the most severe JIA subtype. sJIA typically presents with fever of unknown origin and arthritis, together with evanescent skin rash, serositis, hepatosplenomegaly and lymphadenopathy. It is strongly associated with macrophage activation syndrome (MAS), which has a high fatality rate when untreated. AOSD is phenotypically similar to sJIA in presentation, progression and association with MAS, however it develops after the 16th birthday. The causes sJIA and AOSD are poorly understood.
sJIA and AOSD are diagnoses of exclusion and there are often delays in their diagnosis due to the stringency of their classification criteria. There is no diagnostic test for sJIA/AOSD and there exists significant overlap with other conditions. The manifestations and severity of disease can differ among patients, further delaying the diagnosis. There is also considerable variability in both patient response to therapy and long-term outcomes, and there exist no therapeutic or prognostic biomarkers to guide treatment.
Given our limited understanding of the causes, treatments and prognostic factors of sJIA, we developed this protocol to longitudinally follow patients with sJIA/AOSD and investigate these topics. The specific goals of this protocol include: 1) Establishing a cohort of patients with sJIA/AOSD and assembling a detailed set of longitudinal clinical information; 2) Identifying genetic factors that cause or influence susceptibility to sJIA/AOSD; 3) Determining the functional relevance of genes and variants that influence sJIA/AOSD; and 4) Developing a molecular library of patient biological samples which may be used to further investigate sJIA/AOSD.
Patients enrolled in this protocol will undergo screening history, physical examination and laboratory evaluation. At times, we may ask for permission to evaluate additional family members. We will collect peripheral blood samples for genetic and functional studies from affected patients, unrelated healthy volunteers and in some cases patients' family members. We will ask permission to perform whole genome/exome sequencing. We also may ask some patients to undergo skin biopsy for research purposes. This study aims to elucidate genetic factors that contribute to sJIA/AOSD and related conditions and to determine their implications on inflammatory pathophysiology. By so doing, we hope to identify novel therapeutic targets for inflammatory disease.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA:
- •Affected subject:
- •Patients with signs and symptoms of sJIA will be classified as outlined in Diagnosis/Classification Criteria.
- •Patients less than 16 years of age will be considered to have sJIA if they meet the ILAR criteria for sJIA.
- •Patients 16 years of age and older will be considered to have sJIA if they have previously met ILAR criteria for sJIA.
- •Patients with signs and symptoms of AOSD will be classified as outlined in Yamaguchi Criteria for diagnosing Adult-Onset Still's Disease.
- •Patients 16 years of age and older will be considered to have AOSD if they meet the Yamaguchi criteria for AOSD (including a negative ANA and RF).
- •Patients may be considered to have a diagnosis of AOSD if they met criteria for diagnosis in the past but do not still have present evidence of disease.
- •Pregnant people with still's disease are allowed to enroll. Pregnant people will not be asked to submit to a skin biopsy or bone marrow aspiration.
- •The minimum age for participation in this study is between 0 and older.
- •Healthy Subjects:
- •Healthy Volunteers related to individuals included under items 1 and 2 above will be enrolled.
- •Unrelated healthy volunteers will be enrolled for clinical, cellular, molecular, and biochemical assays, and genetic evaluation. Individuals who undergo phlebotomy specifically to provide a control specimen will include both pediatric and adult patients and will not be pregnant.
- •Healthy Volunteer should not have any history of autoimmune, autoinflammatory, rheumatic or proliferative/malignant disease or any unexplained inflammatory signs/symptoms or conditions (applies to unrelated).
- •The minimum age for participation in this study under this cohort is 2 years.
排除标准
- •Affected and Healthy subjects:
- •In adults, inability, or the lack of capacity to provide informed consent. In the case of minors, unavailability of a parent or guardian.
- •Presence of any medical condition that would, in the opinion of the investigators, confuse the interpretation of the study.
- •Unavailability, or inability to adhere with the schedule for follow-up visits
研究组 & 干预措施
adult-onset Still's disease (AOSD)
Composed of patients with known or suspected AOSD as defined by Yamaguchi criteria.
family members
Composed of family members of patients with systemic juvenile idiopathic arthritis, adult-onset Still's disease and related conditions.
healthy volunteers
Composed of healthy adults and children (above the age of 6 years) who volunteer to participate in this protocol.
related inflammatory conditions
Composed of patients with suspected inflammatory disease as indicated by the presence of episodic fever and/ or arthritis.
systemic juvenile idiopathic arthritis (sJIA)
Composed of patients with known or suspected sJIA as defined by the international league of Associations for Rheumatology (ILAR) criteria
结局指标
主要结局
Genetic sequencing of patients
时间窗: Ongoing
sequencing aims to identify variants to help stratify sJIA, Still's and inflammatory disease patients
次要结局
未报告次要终点