Clinical and Biological Effects of Intramuscular Umbilical Cord-Derived Mesenchymal Stromal Cell Secretome in Patients With Moderate Rheumatoid Arthritis: A Randomized Double-Blind Placebo-Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- ACR20 Response Rate
研究概览
简要总结
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, progressive joint destruction, pain, and functional disability. Although conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are the standard treatment, many patients continue to have active disease despite therapy. Umbilical cord-derived mesenchymal stromal cell (UC-MSC) secretome contains bioactive molecules with immunomodulatory and anti-inflammatory properties that may improve clinical outcomes. This randomized, double-blind, placebo-controlled trial evaluates the efficacy and safety of intramuscular UC-MSC secretome as an adjunct to standard csDMARD therapy in patients with moderate rheumatoid arthritis. Clinical response, inflammatory biomarkers, and adverse events are evaluated throughout the study.
详细描述
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent synovial inflammation, progressive cartilage destruction, bone erosion, and functional disability. Although conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) remain the standard treatment, a substantial proportion of patients continue to experience active disease, highlighting the need for adjunctive therapeutic strategies.
Umbilical cord-derived mesenchymal stromal cell (UC-MSC) secretome is a cell-free biological product containing cytokines, growth factors, extracellular vesicles, and other bioactive molecules with immunomodulatory, anti-inflammatory, and regenerative properties. Compared with live-cell therapy, secretome-based treatment may offer advantages including lower immunogenicity, easier storage and transportation, and standardized manufacturing.
This prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy and safety of intramuscular UC-MSC secretome administered in combination with stable csDMARD therapy in patients with moderate rheumatoid arthritis. Participants were randomly assigned to receive either UC-MSC secretome or placebo in addition to standard treatment. The intervention consisted of six weekly intramuscular injections, followed by protocol-defined clinical and safety follow-up.
The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% improvement response (ACR20). Key secondary endpoints included ACR50 and ACR70 response rates, changes in inflammatory biomarkers (including TNF-α, IL-6, and TGF-β), disease activity, patient-reported outcomes, and treatment safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, care providers administering the study intervention, investigators responsible for clinical management, and outcome assessors were blinded to treatment allocation. UC-MSC secretome and placebo were prepared in identical syringes with identical appearance, volume, and labeling. Randomization codes were generated by an independent statistician and maintained in sealed allocation records until completion of data collection, unless emergency unblinding was required for participant safety. Laboratory personnel performing biomarker analyses remained blinded to treatment allocation until database lock.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •-Adults aged 18 to 60 years.
- •Diagnosis of rheumatoid arthritis according to the 2010 ACR/EULAR Classification Criteria.
- •Moderate disease activity (DAS28-CRP >3.2 and ≤5.1).
- •Receiving stable conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy for at least 3 months before enrollment.
- •Stable dose of corticosteroids and/or NSAIDs for at least 4 weeks before enrollment, if applicable.
- •Willing and able to provide written informed consent.
排除标准
- •Other autoimmune rheumatic diseases or overlap syndromes.
- •Active tuberculosis or other severe active infections.
- •Active hepatitis B, hepatitis C, or HIV infection.
- •History of malignancy.
- •Severe renal impairment or severe hepatic dysfunction.
- •Uncontrolled diabetes mellitus or uncontrolled cardiovascular disease.
- •Pregnancy or breastfeeding.
- •Known hypersensitivity to the study intervention or its components.
- •Participation in another interventional clinical trial within the previous 3 months.
研究组 & 干预措施
UC-MSC Secretome + Standard csDMARD
Participants received 1.5 mL intramuscular umbilical cord-derived mesenchymal stromal cell (UC-MSC) secretome once weekly for six consecutive weeks in addition to stable conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy. Clinical outcomes and biomarkers were evaluated throughout the study and during follow-up.
干预措施: Umbilical Cord-Derived Mesenchymal Stromal Cell (UC-MSC) Secretome (Biological)
Placebo + Standard csDMARD
Participants received 1.5 mL intramuscular placebo (normal saline) once weekly for six consecutive weeks in addition to stable conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy. Clinical outcomes and biomarkers were evaluated throughout the study and during follow-up.
干预措施: Placebo (Normal Saline) (Other)
结局指标
主要结局
ACR20 Response Rate
时间窗: Week 7
Percentage of participants achieving at least a 20% improvement according to the American College of Rheumatology (ACR20) response criteria after 6 weeks of treatment, assessed at Week 7.
次要结局
未报告次要终点