Nebulized MSC-Exos for Anti-MDA5+ RP-ILD: Safety and Efficacy Trial

Официальное название

Safety and Efficacy Study of Nebulized Mesenchymal Stem Cell-Derived Exosomes (MSC-exos) for the Treatment of Anti-MDA5 Positive Dermatomyositis-Associated Rapidly Progressive Interstitial Lung Disease (RP-ILD)

Обзор

Objective: To assess the safety, tolerability, and efficacy of nebulized MSC-exos-P1 in patients with anti-MDA5 positive dermatomyositis-associated rapidly progressive interstitial lung disease (RP-ILD). Design: Prospective interventional trial with 10 eligible patients aged 18-75, meeting criteria for RP-ILD and anti-MDA5 positivity. Primary endpoint is safety and tolerability, measured by adverse events within 30 days post-treatment. Secondary endpoints are clinical improvements on days 14 and 28, including serological indicators and chest HRCT scores. Exclusions: Pregnant/breastfeeding individuals, severe allergies, active pulmonary infections, pulmonary embolism, extracorporeal support treatments, and other specified conditions. Treatment: Nebulized MSC-exos-P1 daily for 14 days, plus standard care of corticosteroids and immunosuppressants. Monitoring: Regular vital signs, oxygenation index, and pulmonary function tests. Follow-ups at multiple points up to 12 months.

Подробное описание

This single-center, prospective interventional trial aims to evaluate the safety profile and potential efficacy of nebulized mesenchymal stem cell-derived exosomes (MSC-exos-P1) in anti-MDA5 positive dermatomyositis patients with rapidly progressive interstitial lung disease. Anti-MDA5 positive RP-ILD represents a critical clinical challenge with mortality rates exceeding 50% despite aggressive immunosuppressive therapy, highlighting the urgent need for novel treatment approaches.

The trial will enroll 10 eligible patients who will receive a 14-day course of daily nebulized MSC-exos-P1 while continuing standard immunosuppressive therapy. Safety monitoring will include daily vital signs, laboratory tests, and adverse event documentation during the treatment period. Efficacy assessments will measure changes in oxygenation parameters, pulmonary function, inflammatory biomarkers, and CT imaging findings at days 14 and 28 compared to baseline.

The scientific rationale for this intervention is based on preclinical evidence demonstrating the immunomodulatory, anti-inflammatory, and anti-fibrotic properties of MSC-derived exosomes. These nanoparticles have shown the ability to modify alveolar macrophage phenotypes, reduce pro-inflammatory cytokine production, and suppress fibroblast activation - mechanisms that may directly target the pathophysiological processes driving RP-ILD in this patient population. The nebulized delivery system enables direct targeting of affected lung tissue while minimizing systemic exposure.

Вмешательства

• Препарат MSC-exos Nebulization Therapy
  The intervention in this study, "Nebulized MSC-exos for Anti-MDA5+ RP-ILD Treatment," is distinguished by its use of mesenchymal stem cell-derived exosomes (MSC-exos) for direct pulmonary delivery via nebulization. This targeted approach aims to modulate immune responses and reduce inflammation specific to lung diseases, offering a novel therapeutic strategy. This method stands out for its potential to provide a safer and more effective treatment for RP-ILD compared to traditional therapies.

Первичные конечные точки

• Three-Month Mortality Rate and Safety of Nebulized MSC-exos P1 [Срок оценки: 3 months post-treatment initiation]]

Вторичные конечные точки (6)

• Oxygen Saturation [Срок оценки: Baseline, day 14, and day 28 post-treatment initiation]
• CT Lesion Changes [Срок оценки: Baseline, day 14, and day 28 post-treatment initiation]
• Symptom Improvement [Срок оценки: Baseline, day 14, and day 28 post-treatment initiation]
• C-reactive Protein (CRP) [Срок оценки: Baseline, day 14, and day 28 post-treatment initiation]
• Interleukin-6 (IL-6) [Срок оценки: Baseline, day 14, and day 28 post-treatment initiation]
• D-dimer [Срок оценки: Baseline, day 14, and day 28 post-treatment initiation]

Критерии участия

Критерии включения

• Patients are eligible for inclusion if they meet all of the following criteria:

• Positive for anti-MDA5 antibody dermatomyositis (according to the "Chinese Expert Consensus on the Diagnosis and Treatment of Anti-MDA5 Positive Dermatomyositis (2023 Edition)");
• Pulmonary lesions meet the diagnostic criteria for RP-ILD.

Критерии исключения

• Patients who meet any of the following criteria will be excluded from this study:

• Pregnant or breastfeeding women, or women planning pregnancy during the study, or men unwilling to use contraceptive measures throughout the trial period;
• History of severe allergies or allergies to the main active ingredients of the trial medication;
• Currently suffering from severe pulmonary infections, pneumothorax, or large pleural effusions;
• Currently diagnosed with pulmonary embolism;
• Currently undergoing mechanical ventilation through tracheal intubation;
• Currently undergoing extracorporeal life support treatments such as ECMO, CRRT, PMX-DHP, or plasma exchange;
• Currently suffering from severe heart failure, liver, or kidney insufficiency;
• Expected to undergo lung transplantation in the near future;
• Currently suffering from lung cancer or pulmonary nodules suspected to be early-stage lung cancer;
• Suffering from primary immunodeficiency diseases;
• Currently suffering from active infectious diseases, including but not limited to HIV positivity, active tuberculosis, etc., and deemed unsuitable for this trial by the researcher;
• Use of other trial medications within 28 days before starting treatment, which the researcher judges may interfere with the safety and efficacy assessment of this trial medication;
• Other situations deemed not in the best interest of the subject or unsuitable for participation in this study by the researcher, such as poor compliance.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Guangzhou Medical University — Гуанчжоу

Идентификаторы

NCT: NCT06919380 · ES-2024 -156 -01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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