Nutritional Therapy Plus Corticosteroids for Immune Checkpoint Inhibitor-Related Pneumonitis

NCT07554885 | Not Yet Recruiting

• 1 other identifier: CROC-CIP-NUT-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immune Checkpoint Inhibitor-Related Pneumonitis; Drug-Related Side Effects and Adverse Reactions; Neoplasms

Keywords

Immune checkpoint inhibitor; Pneumonitis; Immune-related adverse events; Glucocorticoids; Spirulina; Bifidobacterium; Grape seed proanthocyanidin; Ganoderma spore oil; Antioxidant

Outcome Measures

Primary Outcomes (2)

• Time to immune-related pneumonitis downgrading

  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.

  From randomization until first IRRC-confirmed pneumonitis grade reduction of at least 1 grade, assessed up to 6 months

• Proportion of participants with pneumonitis downgrading at 3 months

  Proportion of participants in each arm with an IRRC-confirmed reduction of at least 1 pneumonitis grade from baseline within 3 months after randomization.

  3 months (plus or minus 7 days) after randomization

Secondary Outcomes (7)

• 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

Other Outcomes (3)

• Change in serum KL-6 (Krebs von den Lungen-6)

  Baseline, Day 28, Day 56, Month 2-3

• Change in serum inflammatory cytokines (IL-1 beta, IL-6, IL-10)

  Baseline, Day 28, Day 56, Month 2-3

• Change in immune cell subsets (ALC, CD4+ Th1/Th17, Tregs, NLR, AEC)

  Baseline, Day 28, Day 56, Month 2-3

Study Arms (2)

Nutritional Therapy Plus Glucocorticoid

EXPERIMENTAL

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.

Dietary Supplement: Spirulina-Bifidobacterium capsule; Dietary Supplement: Fish oil-grape seed-blueberry soft capsule; Dietary Supplement: Ganoderma spore oil; Drug: Methylprednisolone

Placebo Plus Glucocorticoid

PLACEBO COMPARATOR

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.

Drug: Methylprednisolone; Other: Matching placebo

Interventions

Spirulina-Bifidobacterium capsule DIETARY_SUPPLEMENT

1080 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.

Nutritional Therapy Plus Glucocorticoid

Fish oil-grape seed-blueberry soft capsule DIETARY_SUPPLEMENT

1200 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.

Nutritional Therapy Plus Glucocorticoid

Ganoderma spore oil DIETARY_SUPPLEMENT

800 mg orally twice daily, from randomization until pneumonitis resolution, intolerance, or death.

Nutritional Therapy Plus Glucocorticoid

Methylprednisolone DRUG

Dose and tapering schedule per investigator assessment, referencing NCCN Guidelines 2025 version 1 for immune-related pneumonitis, continued until clinical and radiologic improvement and then tapered to discontinuation.

Nutritional Therapy Plus Glucocorticoid; Placebo Plus Glucocorticoid

Matching placebo OTHER

Oral placebo capsules identical in appearance, color, shape, size, odor, taste, packaging, label, route, and dosing frequency to the investigational nutritional products, administered to maintain blinding and control for non-specific effects.

Placebo Plus Glucocorticoid

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou Institute of Respiratory Disease: lead

Study Sites (1)

The First Affiliated Hospital of Guangzhou Medical University, Department of Pulmonary Oncology

Guangzhou, Guangdong, 510120, China

Location

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions; Neoplasms; Pneumonia

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Chengzhi Zhou, MD

  The First Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fei Wang

CONTACT

+86 18355293991; doctorlzk@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Eligible participants are randomized 1:1 to either the nutritional therapy plus glucocorticoid arm or the glucocorticoid-only (matching placebo) arm. Stratification factors: tumor type and CIP grade (3 vs 4).

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 28, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

CN (1)