Rheumatoid Arthritis
Conditions
Keywords
UC-MSC Secretome, Randomized Controlled Trial, Immunomodulation, Biologic Therapy, ACR 20
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALUmbilical Cord-Derived Mesenchymal Stromal Cell (UC-MSC) Secretome
Umbilical cord-derived mesenchymal stromal cell (UC-MSC) secretome was administered as a 1.5 mL intramuscular injection once weekly for six consecutive weeks in addition to stable conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy.
OTHERPlacebo (Normal Saline)
Placebo consisting of 1.5 mL normal saline was administered intramuscularly once weekly for six consecutive weeks in addition to stable conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy.
Sponsors
Universitas Sriwijaya
Dr. Mohammad Hoesin General Hospital
PT Bifarma Adiluhung
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
Participants were randomly assigned in a 1:1 ratio to receive either intramuscular umbilical cord-derived mesenchymal stromal cell (UC-MSC) secretome plus stable conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy or placebo plus stable csDMARD therapy. Participants remained in their assigned treatment group throughout the study, and efficacy and safety outcomes were compared between the two parallel groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* -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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACR20 Response Rate | 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. |
Countries
Indonesia
Contacts
STUDY_CHAIRRadiyati Umi Partan, Professor, MD, PhD
Universitas Sriwijaya
Outcome results
None listed