Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still's Disease, and Related Conditions

Arthritis Clinical Trial

Official title: Investigation of the Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still's Disease and Related Inflammatory Conditions

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Autoinflammatory Syndrome
• Inflammation
• Still's Disease, Adult-Onset
• Systemic Inflammation

• NCT number: NCT03510442
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Michelle R Millwood
• Phone: (301) 827-1849
• Email: millwoodmr@mail.nih.gov
• Status: Recruiting
• Start date: May 21, 2018
• Completion date: January 1, 2050