ChiCTR2500106730 版本V1.0 版本创建时间2025/07/29 11:41:24 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2500106730 

最近更新日期：

Date of Last Refreshed on：

 2025-07-29 11:41:19 

注册时间：

Date of Registration：

 2025-07-29 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

低氧诱导因子脯氨酰羟化酶抑制剂对血液透析患者肌少症影响的观察

Public title：

Observation of the Impact of Hypoxia - Inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis Patients

注册题目简写：

HIF-PHI 与血透患者肌少症的关联

English Acronym：

HIF-PHI and Sarcopenia in Hemodialysis Patients

研究课题的正式科学名称：

低氧诱导因子脯氨酰羟化酶抑制剂对血液透析患者肌少症影响的观察

Scientific title：

Observation of the Impact of Hypoxia - Inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis Patients

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

徐鹏程 

研究负责人：

贾俊亚 

Applicant：

Pengcheng Xu 

Study leader：

Junya Jia 

申请注册联系人电话：

Applicant telephone：

 +86 138 2058 3382

研究负责人电话：

Study leader's
telephone：

+86 138 2173 5536

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 nkxpc@163.com

研究负责人电子邮件：

Study leader's E-mail：

 jiajunya@126.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

天津市和平区鞍山道154号

研究负责人通讯地址：

天津市和平区鞍山道154号

Applicant address：

No. 154, Anshan Road, Heping District, Tianjin, 300052, China

Study leader's address：

No. 154, Anshan Road, Heping District, Tianjin, 300052, China

申请注册联系人邮政编码：

Applicant postcode：

 300052

研究负责人邮政编码：

Study leader's postcode：

 300052

申请人所在单位：

天津医科大学总医院肾脏内科

Applicant's institution：

Department of Nephrology, Tianjin Medical University General Hospital

研究负责人所在单位：

天津医科大学总医院肾脏内科

Affiliation of the Leader：

Department of Nephrology, Tianjin Medical University General Hospital

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 IRB2025-YX-317-01

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

天津医科大学总医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Tianjin Medical University General Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-06-26 00:00:00

伦理委员会联系人：

常虹

Contact Name of the ethic committee：

Hong Chang

伦理委员会联系地址：

天津市和平区鞍山道154号

Contact Address of the ethic committee：

No. 154, Anshan Road, Heping District, Tianjin, 300052, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 22 6036 3203

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

天津医科大学总医院肾脏内科

Primary sponsor：

Department of Nephrology, Tianjin Medical University General Hospital

研究实施负责（组长）单位地址：

天津市和平区鞍山道154号

Primary sponsor's address：

No. 154, Anshan Road, Heping District, Tianjin, 300052, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

天津市

市(区县)：

和平区

Country：

China

Province：

Tianjin

City：

Heping District

单位(医院)：

天津医科大学总医院肾脏内科

具体地址：

天津市和平区鞍山道154号

Institution
hospital：

Department of Nephrology, Tianjin Medical University General Hospital

Address：

No. 154, Anshan Road, Heping District, Tianjin, 300052, China

经费或物资来源：

自筹经费

Source(s) of funding：

Self-financing

研究疾病：

肌少症  

Target disease：

Sarcopenia

研究疾病代码：

ICD-10-CM(M62.84)

Target disease code：

ICD-10-CM(M62.84)

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

肌肉减少症（sarcopenia），简称肌少症，是慢性肾脏病（chronic kidney disease， CKD）患者，尤其是终末期肾病（end?stage renal disease， ESRD）患者常见的并发症，严重影响患者的生活质量。是指进行性、广泛性的骨骼肌含量减少及功能减退的疾病。临床上主要表现为肌肉含量减少、肌力及躯体功能下降。肌少症最早在老年人群中被发现和定义。维持性血液透析（maintenance hemodialysis, MHD）患者肌少症患病率高达 32.7%～73.5%，远高于普通人群（5%～13%）。肌少症使MHD患者的死亡风险显著升高：肌少症患者全因死亡率心血管事件风险上升，生活质量下降，跌倒、骨折风险增高。因此治疗肌少症对于MHD患者具有重要意义。 目前认为MHD患者肌少症的主要原因可能有：营养代谢失衡，透析过程导致氨基酸大量丢失，且患者常因食欲不振致蛋白质摄入不足；慢性炎症状态，微炎症激活加速肌肉分解，导致肌肉质量下降；代谢性酸中毒、胰岛素抵抗及维生素D缺乏进一步加剧肌肉消耗。虽然针对这些因素进行积极干预可在一定程度上改善肌少症，但对于多数患者往往效果并不理想，探索针对肌少症的药物治疗有着很重要的意义。HIF-1（缺氧诱导因子-1）通路与肌少症之间存在密切的病理生理联系，HIF-1α是细胞应对缺氧环境的关键转录因子。正常氧条件下，HIF-1α被脯氨酰羟化酶（PHD）羟基化，经泛素化降解；缺氧时HIF-1α稳定表达，入核后激活下游靶基因。HIF-1α促进糖酵解相关基因（如GLUT1、LDHA）表达，抑制线粒体氧化磷酸化，导致骨骼肌能量代谢从有氧向无氧转化。研究发现，肌少症患者的 HIF-1α蛋白水平显著降低。这些结果表明，负责细胞对缺氧应激反应的机制受损，对于肌肉再生过程的激活至关重要。通过激活 HIF-1α及其靶基因可以减少骨骼肌萎缩。 口服药物罗沙司他（Roxadustat）胶囊是全球首个开发的小分子低氧诱导因子脯氨酰羟化酶抑制剂（HIF-PHI）类治疗肾性贫血的药物。HIF-1α的生理作用不仅使红细胞生成素表达增加，也能使红细胞生成素受体以及促进铁吸收和循环的蛋白表达增加。罗沙司他通过模拟脯氨酰羟化酶（PH）的底物之一酮戊二酸来抑制PH酶，影响PH酶在维持HIF生成和降解速率平衡方面的作用，从而达到纠正贫血的目的。除用于肾性贫血外，在其他类型的贫血中目前也有广泛应用。 从理论上说，罗沙司他是一种有改善肌少症潜力的药物，但由于其改善贫血的作用比较突出，目前在临床上只能应用于贫血的患者。血液透析患者的肾性贫血发生非常普遍，既往主要通过注射重组红细胞生成素（ESA）的方法纠正贫血，虽然这些方法可以治疗贫血，但理论上对肌少症并无作用，既往研究表明罗沙司他改善肾性贫血的能力较注射重组红细胞生成素更强，但尚无二者在对于血液透析患者肌少症改善方面的影响的比较研究。因此本研究拟以ESA为对照，观察血液透析患者使用罗沙司他治疗肾性贫血时对合并肌少症的作用。  

Objectives of Study：

Sarcopenia, abbreviated as muscle wasting disorder, is a prevalent complication among patients with chronic kidney disease (CKD), particularly those with end - stage renal disease (ESRD). It significantly impairs patients' quality of life. Sarcopenia refers to a disorder characterized by progressive and widespread decline in skeletal muscle mass and functional deterioration. Clinically, it presents as a reduction in muscle mass, diminished muscle strength, and decline in physical function. Sarcopenia was initially identified and defined within the elderly population. The prevalence of sarcopenia in patients undergoing maintenance hemodialysis (MHD) ranges from 32.7% to 73.5%, far exceeding that of the general population (5% - 13%). Sarcopenia substantially elevates the mortality risk in MHD patients. Specifically, it increases the all - cause mortality rate, the risk of cardiovascular events, deteriorates the quality of life, and heightens the risks of falls and fractures. Thus, the treatment of sarcopenia holds great significance for MHD patients. Currently, the primary factors contributing to sarcopenia in MHD patients are postulated to include: nutritional and metabolic imbalance. During dialysis, a large quantity of amino acids is lost, and patients often have insufficient protein intake due to anorexia; a chronic inflammatory state, where micro - inflammation activation accelerates muscle catabolism, resulting in a decrease in muscle mass; metabolic acidosis, insulin resistance, and vitamin D deficiency further exacerbate muscle wasting. Although active interventions targeting these factors can, to some extent, ameliorate sarcopenia, the outcomes are frequently suboptimal for the majority of patients. Therefore, exploring pharmacological treatments for sarcopenia is of substantial academic and clinical importance. There exists a close pathophysiological association between the hypoxia - inducible factor - 1 (HIF - 1) pathway and sarcopenia. HIF - 1α serves as a pivotal transcription factor for cells to respond to hypoxic conditions. Under normoxic circumstances, HIF - 1α is hydroxylated by prolyl hydroxylase (PHD) and subsequently degraded via ubiquitination. Conversely, under hypoxic conditions, HIF - 1α is stably expressed, translocates into the nucleus, and activates downstream target genes. HIF - 1α promotes the expression of genes associated with glycolysis (such as GLUT1 and LDHA), inhibits mitochondrial oxidative phosphorylation, thereby leading to a shift in skeletal muscle energy metabolism from aerobic to anaerobic. Research has revealed that the protein level of HIF - 1α is significantly decreased in patients with sarcopenia. These findings suggest that the mechanism responsible for the cellular response to hypoxic stress is impaired, which is crucial for activating the muscle regeneration process. Activation of HIF - 1α and its target genes can mitigate skeletal muscle atrophy. Roxadustat capsules, an orally administered medication, represent the world's first developed small - molecule hypoxia - inducible factor prolyl hydroxylase inhibitor (HIF - PHI) for the treatment of renal anemia. The physiological function of HIF - 1α not only enhances the expression of erythropoietin but also upregulates the expression of erythropoietin receptors and proteins that facilitate iron absorption and circulation. Roxadustat inhibits PH enzymes by mimicking ketoglutarate, one of the substrates of PH, thereby influencing the role of PH enzymes in maintaining the equilibrium between HIF production and degradation rates, ultimately achieving the correction of anemia. Beyond its application in renal anemia, roxadustat is currently also widely utilized in other types of anemia. Theoretically, roxadustat holds promise as a potential treatment for sarcopenia. However, due to its prominent efficacy in treating anemia, it is currently clinically indicated only for anemic patients. Renal anemia is highly prevalent among hemodialysis patients. Historically, anemia was predominantly managed through the injection of recombinant erythropoietin (ESA). Although these approaches can effectively treat anemia, in theory, they have no impact on sarcopenia. Previous research has demonstrated that roxadustat exhibits a greater efficacy in improving renal anemia compared to ESA injection. Nevertheless, there is a lack of comparative studies regarding the impact of these two treatments on sarcopenia in hemodialysis patients. Hence, this study aims to use ESA as a control to investigate the effect of roxadustat on co - existing sarcopenia when used to treat renal anemia in hemodialysis patients.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

年龄18–80岁，维持性血液透析≥3个月；患者同时存在肾性贫血和肌少症。 肾性贫血的诊断标准为Hb 70–100 g/L，且eGFR <15 mL/min/1.73m2。

Inclusion criteria

Patients aged 18 to 80 years old, with maintenance hemodialysis for at least 3 months; patients have both renal anemia and sarcopenia simultaneously. The diagnostic criteria for renal anemia are Hb 70 - 100 g/L and eGFR < 15 mL/min/1.73m^2.

排除标准：

合并活动性感染（CRP >20 mg/L） 合并恶性肿瘤 ESA抵抗史（EPO >300 IU/kg/周仍Hb <110 g/L）。 实验室异常：铁过载（SF >800 μg/L或TSAT >50%） 高钾血症（血钾>5.5 mmol/L，透析前） 特殊禁忌： 妊娠、计划肾移植、严重肝功能不全（Child-Pugh C），3个月内使用雄激素或免疫抑制剂

Exclusion criteria：

Active infection (CRP > 20 mg/L) Malignant tumor History of ESA resistance (Hb < 110 g/L despite EPO > 300 IU/kg/week) Laboratory abnormalities: Iron overload (SF > 800 μg/L or TSAT > 50%) Hyperkalemia (serum potassium > 5.5 mmol/L before dialysis) Special contraindications: Pregnancy, planned kidney transplantation, severe liver dysfunction (Child-Pugh C), use of androgens or immunosuppressants within 3 months

研究实施时间：

Study execute time：

从 From 2025-08-01 00:00:00至 To 2026-08-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-08-01 00:00:00 至 To 2026-08-01 00:00:00

干预措施：

Interventions：

组别：

1

样本量：

 30

Group：

1

Sample size：

干预措施：

罗沙司他

干预措施代码：

Intervention：

Roxadustat

Intervention code：

组别：

2

样本量：

 30

Group：

2

Sample size：

干预措施：

促红细胞生成素

干预措施代码：

Intervention：

Erythropoietin

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 天津市 

市(区县)：

 和平区 

Country：

China

Province：

Tianjin

City：

Heping District

单位(医院)：

 天津医科大学总医院 

单位级别：

 三甲 

Institution
hospital：

Tianjin Medical University General Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

血红蛋白

指标类型：

主要指标

Outcome：

hemoglobin

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肌肉含量

指标类型：

主要指标

Outcome：

Muscle mass

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 80 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

简单随机化方法，由研究者通过随机数表产生随机序列。

Randomization Procedure (please state who generates the random number sequence and by what method)：

The simple randomization method involves the researcher generating a random sequence through a random number table.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

无

Blinding：

None

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

None

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

无

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

None

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2025-07-29 11:41:19