优化晚期肺癌患者的肌肉质量和功能：使用高二十碳五烯酸和蛋白质（HEPRO）调节表观遗传学、降低毒性并改善肠道微生物群的随机、双盲、安慰剂对照试验方案
Optimizing muscle mass and function in advanced lung cancer patients: randomized, double-blind, placebo-controlled trial protocol using High Eicosapentaenoic acid and PROtein (HEPRO) to modulate epigenetics, reduce toxicity and improve gut microbiota.
作者信息
Borchardt Imanuely, Prado Carla, Montella Tatiane, Moreira Gisele Fraga, Farias Gisele, Reis Marina Xavier, Taveira Fernanda, Dias Fernanda Carneiro, De Marchi Pedro, Davalos Alberto, Silva Carolina Alves Costa, Ferreira Carlos GilMoreira, Melo Andreia, Peres Wilza
机构信息
Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Oncoclínicas & Co-Medica Scientia Innovation Research, São Paulo, São Paulo, Brazil.
出版信息
PeerJ. 2025 Jun 3;13:e19506. doi: 10.7717/peerj.19506. eCollection 2025.
BACKGROUND
Lung cancer is strongly associated with malnutrition and detrimental changes in muscle mass (MM), which can lead to reduced quality of life and reduced tolerance to and efficacy of antineoplastic treatment. The loss of MM and myosteatosis (fat infiltration into muscle) have been linked to inflammation in cancer, and n-3 polyunsaturated fatty acids (PUFA) found in fish oil are known to modulate inflammatory response, lean mass, microbiota, and epigenetic mechanisms.
METHODS
High Eicosapentaenoic acid and PROtein (HEPRO) is a randomized, double-blind, placebo-controlled clinical trial. A total of 50 patients over 20 years of age diagnosed with stage III or IV non-small cell lung cancer with an ECOG performance status of 0-2 who are eligible for systemic treatment will be included and randomized 1:1 into two treatment arms: four fish oil capsules containing 2,100 mg EPA and 924 mg DHA per day versus four placebo capsules containing 2,250 mg oleic acid per day for 4 months. All patients will be instructed to consume 1.5 g protein per kg body weight per day and receive protein supplementation if necessary. MM, myosteatosis, muscle function, handgrip strength, dietary assessment, toxicity, response to treatment, and survival will be assessed. Translational research includes membrane phospholipid composition, gut microbiota, inflammation, and miRNA. MicroRNA will be analyzed by quantitative real-time polymerase chain reaction, phospholipids, by gas chromatography, and microbiota, by 16S ribosomal RNA genetic sequencing. Statistical analysis will be conducted using IBM SPSS Statistics V.26 and a multiple regression model will be proposed. Associations with < 0.05 will be considered significant.
CONCLUSIONS
The HEPRO study aims to evaluate a viable dietary intervention strategy to improve MM and function in patients with lung cancer.
背景
肺癌与营养不良以及肌肉量（MM）的有害变化密切相关，这会导致生活质量下降，以及对抗肿瘤治疗的耐受性和疗效降低。MM的丧失和肌脂肪变性（脂肪浸润到肌肉中）与癌症炎症有关，而鱼油中含有的n-3多不饱和脂肪酸（PUFA）已知可调节炎症反应、瘦体重、微生物群和表观遗传机制。
方法
高二十碳五烯酸和蛋白质（HEPRO）是一项随机、双盲、安慰剂对照的临床试验。将纳入总共50名20岁以上、诊断为III期或IV期非小细胞肺癌、东部肿瘤协作组（ECOG）体能状态为0 - 2且有资格接受全身治疗的患者，并按1:1随机分为两个治疗组：每天服用四粒含2100毫克二十碳五烯酸（EPA）和924毫克二十二碳六烯酸（DHA）的鱼油胶囊，与每天服用四粒含2250毫克油酸的安慰剂胶囊，持续4个月。所有患者将被指导每天每公斤体重摄入1.5克蛋白质，必要时接受蛋白质补充。将评估MM、肌脂肪变性、肌肉功能、握力、饮食评估、毒性、治疗反应和生存率。转化研究包括膜磷脂组成、肠道微生物群、炎症和微小RNA（miRNA）。miRNA将通过定量实时聚合酶链反应进行分析，磷脂通过气相色谱法分析，微生物群通过16S核糖体RNA基因测序分析。将使用IBM SPSS Statistics V.26进行统计分析，并提出多元回归模型。P < 0.05的关联将被视为具有统计学意义。
结论
HEPRO研究旨在评估一种可行的饮食干预策略，以改善肺癌患者的MM和功能。
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