Therapeutic Value of Sirolimus in Refractory Adult-Onset Still's Disease

NCT07151157 | Active Not Recruiting

• 1 other identifier: 2025-495
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to further evaluate the anti-inflammatory effects of the mTOR inhibitor sirolimus in patients with adult-onset Still's disease (AOSD), and to verify whether it can reduce inflammation and control disease activity by restoring ZFP36L2 expression and promoting the degradation of inflammatory cytokine mRNAs. A total of three patients with refractory AOSD will be enrolled, defined as those showing no significant improvement after treatment with glucocorticoids at 1 mg/kg, or experiencing relapse during tapering of glucocorticoids to 15 mg/day. On the basis of their existing therapy, patients will receive oral sirolimus at a dose of two capsules per day, one in the morning and one in the evening. On the day prior to initiating sirolimus and at weeks 4, 8, and 12 of treatment, 10 ml of peripheral blood will be collected by trained medical staff, and neutrophils will be isolated within 2 hours to assess ZFP36L2 expression levels. Throughout treatment, patients' clinical manifestations, including fever, rash, and joint pain, will be monitored, and dynamic changes in multiple inflammation-related markers will be measured in peripheral blood at weeks 4, 8, and 12. These include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, soluble interleukin-2 receptor (sIL-2R), and a panel of cytokines. Finally, correlations among sirolimus treatment, ZFP36L2 expression, inflammatory responses, and disease activity will be analyzed to explore its potential therapeutic mechanisms in AOSD.

Conditions

Adult-Onset Still's Disease

Keywords

Adult-Onset Still's disease; sirolimus; mTOR; ZFP36L2

Outcome Measures

Primary Outcomes (1)

• AOSD Disease Activity Score

  Pouchot Systemic Score Scoring items (1 point each): fever; arthritis/arthralgia; rash; sore throat; hepatosplenomegaly; pericarditis/pleuritis; lymphadenopathy; abnormal liver function; leukocytosis; hyperamylasemia/thrombocytopenia; elevated ESR or CRP; other systemic manifestations (e.g., myalgia, fatigue). Total score: 0-12 points, with higher scores indicating greater disease activity.

  at weeks 12

Secondary Outcomes (8)

• AOSD Disease Activity Score

  Baseline (day before sirolimus) and at weeks 4, and 8

• Serum C-reactive Protein (CRP) Concentration

  Baseline (day before sirolimus) and at weeks 4, 8, and 12

• Erythrocyte Sedimentation Rate (ESR)

  Baseline (day before sirolimus) and at weeks 4, 8, and 12

• Concentration of Serum Ferritin

  Baseline (day before sirolimus) and at weeks 4, 8, and 12

• Level of Soluble Interleukin-2 Receptor (sIL-2R)

  Baseline (day before sirolimus) and at weeks 4, 8, and 12

Study Arms (1)

Sirolimus combination therapy group

EXPERIMENTAL

On the basis of the existing treatment, oral sirolimus will be added at a dose of two capsules per day, one in the morning and one in the evening.

Drug: add-on sirolimus therapy

Interventions

add-on sirolimus therapy DRUG

On the basis of the existing treatment, oral sirolimus will be added at a dose of two capsules per day, one in the morning and one in the evening.

Sirolimus combination therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age over 18 years;
• Meeting the Yamaguchi criteria, with infection and malignancy excluded;
• Meeting the definition of refractory AOSD, i.e., patients whose symptoms show no significant improvement after treatment with glucocorticoids at 1 mg/kg, or who experience relapse during tapering of glucocorticoids to 15 mg/d;
• Complete clinical information;
• Signed and dated informed consent form;
• Willingness to comply with study procedures and cooperate throughout the entire study.

You may not qualify if:

• Presence of other rheumatic diseases;
• History of, or planned, hematopoietic stem cell transplantation;
• Presence of severe comorbidities considered by the investigator to be unsuitable for participation in this clinical study, such as severe cardiac or pulmonary insufficiency, severe bone marrow suppression, or severe hepatic or renal dysfunction;
• Acute conditions such as bowel perforation or complete intestinal obstruction;
• Pregnant, planning pregnancy, or breastfeeding women;
• Poor compliance.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruiiin Hospital Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Still's Disease, Adult-Onset

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2025
• First Posted: September 3, 2025
• Study Start: August 30, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: November 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)