A Single-Center, Open-Label, Randomized Controlled Clinical Trial Comparing Nutritional Therapy (Spirulina-Bifidobacterium Capsules, Fish Oil-Grape Seed-Blueberry Soft Capsules, and Ganoderma Spore Oil) Combined With Standard Glucocorticoid Regimen Versus Standard Glucocorticoid Regimen Alone in the Treatment of Immune Checkpoint Inhibitor-Related Pneumonitis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Time to immune-related pneumonitis downgrading
研究概览
简要总结
This is a prospective, single-center, open-label, randomized controlled clinical trial evaluating whether the addition of a nutritional therapy regimen (Spirulina-Bifidobacterium capsules, fish oil-grape seed-blueberry soft capsules, and Ganoderma spore oil) to standard glucocorticoid therapy improves outcomes in patients with Grade 3-4 immune checkpoint inhibitor-related pneumonitis (CIP), compared with standard glucocorticoid therapy alone.
A total of 60 patients with malignancies who develop Grade 3-4 CIP (per CTCAE v5.0) after at least one cycle of immune checkpoint inhibitor therapy will be randomized 1:1 to the experimental or control arm. The primary endpoints are time to pneumonitis downgrading and the proportion of patients achieving downgrading at 3 months.
详细描述
BACKGROUND:
Immune checkpoint inhibitor-related pneumonitis (CIP) accounts for the largest proportion of fatal immune-related adverse events. Approximately 30% of patients respond poorly to corticosteroid therapy, and long-term high-dose steroids increase the risk of secondary infection. Oxidative stress plays a key role in pulmonary fibrosis. The investigational nutritional products have demonstrated antioxidant and immunomodulatory properties in preclinical and clinical studies.
OBJECTIVES:
Primary: To evaluate the efficacy of nutritional therapy combined with glucocorticoids versus glucocorticoids alone in treating CIP, as measured by time to pneumonitis downgrading and the 3-month downgrading rate.
Secondary: To evaluate safety (AE/SAE incidence, severity), total steroid dose and duration, and changes in 6-minute walk distance (6MWD), modified Medical Research Council dyspnea scale (mMRC), St George's Respiratory Questionnaire (SGRQ), and Leicester Cough Questionnaire (LCQ).
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
- Double (Participant, Outcomes Assessor)
盲法说明
The control arm receives matching placebo capsules identical in appearance, color, shape, size, odor, taste, packaging, label, route, and dosing frequency to the investigational nutritional products. Pneumonitis imaging is assessed by an Independent Radiologic Review Committee blinded to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation with full understanding of the study and signed informed consent form.
- •Age 18 to 75 years (inclusive) on the day of informed consent signing.
- •Histologically or cytologically confirmed malignancy.
- •Received at least one cycle of immune checkpoint inhibitor therapy.
- •Grade 3-4 immune-related pneumonitis (per CTCAE v5.0 and radiologic grading).
- •ECOG performance status 0-2, with expected survival of more than 3 months.
- •Adequate organ function based on laboratory results (without transfusion, apheresis, erythropoietin, or granulocyte colony-stimulating factor support within 14 days before the first dose). Women of childbearing potential must have a negative serum pregnancy test within 7 days before first dose.
排除标准
- •Severe cardiac, cerebrovascular, renal, hematologic, or other serious systemic disease, including: NYHA Class III-IV heart failure; acute myocardial infarction or unstable angina within 6 months; severe post-stroke functional impairment (mRS greater than or equal to 3); progressive neurodegenerative disease; Child-Pugh Class B or C liver disease or acute liver failure; CKD stage 4-5 (eGFR less than 30 mL/min/1.73 m2) or requiring dialysis; absolute neutrophil count less than 1.5 x 10^9/L, platelet count less than 50 x 10^9/L, or Grade 3 or higher anemia (Hb less than 8 g/dL).
- •Severe allergic constitution or contraindications to the study treatment.
- •Significant psychiatric or psychological disorder, or doubts about the treatment plan.
- •Investigator judgment that the patient is unsuitable for the trial (e.g., poor follow-up adherence, refusal of supportive care).
- •Use of anti-tumor traditional Chinese medicine within 14 days before first dose.
- •History of or active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- •Severe acute or chronic infection.
- •Known alcohol or drug abuse history.
- •Pregnancy or breastfeeding.
- •Use of antibiotics, probiotic food, or microecological preparations within 2 weeks before enrollment.
- •Prior treatment-related lung injury: (a) targeted-therapy-related pulmonary toxicity (prior EGFR-TKI, ALK inhibitor, VEGF inhibitor, or antibody-drug conjugate causing interstitial lung disease or pneumonitis that has not fully resolved, with radiologic fibrosis or persistent functional impairment); (b) thoracic radiation-related lung injury (radiation pneumonitis or radiation fibrosis with irreversible CT findings).
- •Use of another investigational drug within 28 days before first dose that, per investigator judgment, would interfere with evaluation of study treatment.
- •Gastrointestinal disorder precluding oral administration.
研究组 & 干预措施
Nutritional Therapy Plus Glucocorticoid
Participants receive Spirulina-Bifidobacterium capsules 1080 mg orally twice daily, fish oil-grape seed-blueberry soft capsules 1200 mg orally twice daily, and Ganoderma spore oil 800 mg orally twice daily, in addition to methylprednisolone administered per investigator assessment (referencing NCCN Guidelines 2025 v1), until pneumonitis resolution, intolerance, or death.
干预措施: Methylprednisolone (Drug)
Nutritional Therapy Plus Glucocorticoid
Participants receive Spirulina-Bifidobacterium capsules 1080 mg orally twice daily, fish oil-grape seed-blueberry soft capsules 1200 mg orally twice daily, and Ganoderma spore oil 800 mg orally twice daily, in addition to methylprednisolone administered per investigator assessment (referencing NCCN Guidelines 2025 v1), until pneumonitis resolution, intolerance, or death.
干预措施: Ganoderma spore oil (Dietary Supplement)
Nutritional Therapy Plus Glucocorticoid
Participants receive Spirulina-Bifidobacterium capsules 1080 mg orally twice daily, fish oil-grape seed-blueberry soft capsules 1200 mg orally twice daily, and Ganoderma spore oil 800 mg orally twice daily, in addition to methylprednisolone administered per investigator assessment (referencing NCCN Guidelines 2025 v1), until pneumonitis resolution, intolerance, or death.
干预措施: Fish oil-grape seed-blueberry soft capsule (Dietary Supplement)
Nutritional Therapy Plus Glucocorticoid
Participants receive Spirulina-Bifidobacterium capsules 1080 mg orally twice daily, fish oil-grape seed-blueberry soft capsules 1200 mg orally twice daily, and Ganoderma spore oil 800 mg orally twice daily, in addition to methylprednisolone administered per investigator assessment (referencing NCCN Guidelines 2025 v1), until pneumonitis resolution, intolerance, or death.
干预措施: Spirulina-Bifidobacterium capsule (Dietary Supplement)
Placebo Plus Glucocorticoid
Participants receive matching placebo capsules (identical in appearance, color, shape, size, odor, taste, packaging, label, route, and dosing frequency to the investigational nutritional products) in addition to methylprednisolone administered per investigator assessment (referencing NCCN Guidelines 2025 v1), tapered until symptoms and imaging improve and then discontinued.
干预措施: Matching placebo (Other)
Placebo Plus Glucocorticoid
Participants receive matching placebo capsules (identical in appearance, color, shape, size, odor, taste, packaging, label, route, and dosing frequency to the investigational nutritional products) in addition to methylprednisolone administered per investigator assessment (referencing NCCN Guidelines 2025 v1), tapered until symptoms and imaging improve and then discontinued.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Time to immune-related pneumonitis downgrading
时间窗: From randomization until first IRRC-confirmed pneumonitis grade reduction of at least 1 grade, assessed up to 6 months
Time from randomization to the first imaging assessment, confirmed by the Independent Radiologic Review Committee, showing a reduction of at least 1 grade in pneumonitis severity compared with baseline, per CTCAE v5.0 and radiologic grading.
Proportion of participants with pneumonitis downgrading at 3 months
时间窗: 3 months (plus or minus 7 days) after randomization
Proportion of participants in each arm with an IRRC-confirmed reduction of at least 1 pneumonitis grade from baseline within 3 months after randomization.
次要结局
- Change from baseline in 6-minute walk distance (6MWD)(Baseline, Day 28, Day 56, Month 2-3)
- Change from baseline in modified Medical Research Council (mMRC) dyspnea scale(Baseline, Day 28, Day 56, Month 2-3)
- Change from baseline in St George's Respiratory Questionnaire (SGRQ) total score(Baseline, Day 28, Day 56, Month 2-3)
- Change from baseline in Leicester Cough Questionnaire (LCQ) score(Baseline, Day 28, Day 56, Month 2-3)
- Total cumulative corticosteroid dose(From randomization to end of corticosteroid treatment, up to approximately 6 months)
- Duration of corticosteroid treatment(From randomization to end of corticosteroid treatment, up to approximately 6 months)
- Incidence of adverse events, treatment-related adverse events, and serious adverse events(From randomization through 30 days after last dose; SAEs collected through 90 days after last dose)
研究者
Zhou Chengzhi
Principal Investigator
Guangzhou Institute of Respiratory Disease