Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis Patients

NCT07162090 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: IRB2025-YX-317-01
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Sarcopenia, abbreviated as muscle loss, is a prevalent complication among patients with chronic kidney disease (CKD), particularly those with end - stage renal disease (ESRD). It significantly impacts patients' quality of life. The prevalence of sarcopenia in patients receiving maintenance hemodialysis (MHD) ranges from 32.7% to 73.5%, which is substantially higher than that in the general population (5% - 13%). Sarcopenia significantly elevates the mortality risk in MHD patients. Specifically, sarcopenia patients experience an increased all - cause mortality rate, a heightened risk of cardiovascular events, a decline in quality of life, and an augmented risk of falls and fractures. A close pathophysiological relationship exists between the hypoxia - inducible factor - 1 (HIF - 1) pathway and sarcopenia. HIF - 1α serves as a key transcription factor for cells to respond to hypoxic conditions. Under normoxic conditions, HIF - 1α is hydroxylated by prolyl hydroxylase (PHD) and subsequently undergoes ubiquitination - mediated degradation. Conversely, under hypoxic circumstances, 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, while inhibiting mitochondrial oxidative phosphorylation. This results in a shift of skeletal muscle energy metabolism from aerobic to anaerobic pathways. Research has revealed that the protein level of HIF - 1α is significantly decreased in sarcopenia patients. Roxadustat capsules, an oral medication, represent the world's first small - molecule hypoxia - inducible factor prolyl hydroxylase inhibitor (HIF - PHI) developed 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 involved in promoting iron absorption and circulation. Theoretically, roxadustat has the potential to improve sarcopenia. However, due to its prominent effect on anemia correction, it is currently only clinically applicable to anemic patients. This study aims to use ESA as a control to investigate the effect of roxadustat on sarcopenia in hemodialysis patients during the treatment of renal anemia.

Conditions

Sarcopenia; Anemia Associated With Chronic Kidney Disease (CKD); Dialysis Patients

Keywords

Sarcopenia; Anemia

Outcome Measures

Primary Outcomes (4)

• The impacts of different drug therapies (roxadustat or erythropoietin) on the sarcopenia status of patients

  The risk of sarcopenia in patients was evaluated using the SARC-Calf assessment form.

  16 weeks

• The impacts of different drug therapies (roxadustat or erythropoietin) on the sarcopenia status of patients

  Muscle strength was measured by employing a handgrip dynamometer on the dominant hand of the patients.

  16 weeks

• The impacts of different drug therapies (roxadustat or erythropoietin) on the sarcopenia status of patients

  The muscle area at the L3 level was assessed via CT scan.

  16 weeks

• The impacts of different drug therapies (roxadustat or erythropoietin) on the sarcopenia status of patients

  The locomotor ability of patients was evaluated through the 6-meter walking test.

  16 weeks

Secondary Outcomes (5)

• The impacts of two distinct drug therapies on the amelioration of renal anemia in patients

  16 weeks

• The impacts of two distinct drug therapies on the amelioration of renal anemia in patients

  16 weeks

• The impacts of two distinct drug therapies on the amelioration of renal anemia in patients

  16 weeks

• The impacts of two distinct drug therapies on the amelioration of renal anemia in patients

  16 weeks

• The impacts of two distinct drug therapies on the amelioration of renal anemia in patients

  16 weeks

Other Outcomes (2)

• The incidences of adverse events in the two groups of patients

  16 weeks

• The incidences of adverse events in the two groups of patients

  16 weeks

Study Arms (2)

Patients receiving treatment with Roxadustat

EXPERIMENTAL

Roxadustat is administered at an initial dose of 50 mg per oral administration, three times a week. Complete blood count and serum iron levels are re - evaluated monthly. The dosage is adjusted based on the rate of increase in hemoglobin levels. Observations were made every six weeks starting from the initiation of treatment, and the entire observation period lasted for 24 weeks.

Drug: Roxadustat

Patients receiving treatment with recombinant human erythropoietin

ACTIVE COMPARATOR

For recombinant human erythropoietin, the initial dosage is 3000 international units (IU) per administration. It is administered via subcutaneous injection three times a week. The blood routine and serum iron levels are re - examined monthly. The dosage is adjusted according to the rate of increase in hemoglobin. Observations were made every six weeks starting from the initiation of treatment, and the entire observation period lasted for 24 weeks.

Drug: Recombinant human erythropoietin (EPO)

Interventions

Roxadustat DRUG

Patients were administered roxadustat orally to observe its impacts on renal anemia and sarcopenia.

Also known as: HIF-PHI

Patients receiving treatment with Roxadustat

Recombinant human erythropoietin (EPO) DRUG

Recombinant human erythropoietin was administered to patients as a control group to investigate its impacts on renal anemia and sarcopenia.

Also known as: rHuEPO

Patients receiving treatment with recombinant human erythropoietin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 to 80 years old (inclusive), gender unrestricted.
• End-stage renal disease and maintenance hemodialysis for at least 16 weeks.
• The average Hb level is 7.0\~10.0 g/dL (the last two evaluations).
• And have not received or have discontinued ESA/roxadustat treatment.
• Vascular access: internal fistula or long-term hemodialysis catheter.
• Weight between 45-100 kg.
• Sarcopenia Diagnosis (Reference: AWGS 2019 Consensus):
• Decreased muscle strength: Male grip strength \< 28 kg, female grip strength \< 18 kg.
• Muscle mass decline: Assessed by bioelectrical impedance analysis (BIA) or dual-energy X-ray absorptiometry (DXA), it is characterized by appendicular skeletal muscle mass index (ASMI): \< 7.0 kg/m² for men and \< 5.7 kg/m² for women (BIA standard, the device and formula used should be specified).
• Sarcopenia can be diagnosed when both "decreased muscle strength" and "reduced muscle mass" are present. If resources permit, "decreased physical function" (such as a 6-meter walking speed \< 1.0 m/s) can be added as an indicator for severity grading.
• Voluntary participation in this study.
• Must be able to swallow tablets。

You may not qualify if:

• Non-renal anemia: Anemia caused by other main reasons (such as thalassemia, megaloblastic anemia due to vitamin B12 or folic acid deficiency, active bleeding, hemolytic anemia, hematological malignancies, etc.).
• Contraindications and related risks of Roxadustat:
• People who are allergic to roxadustat or any of its excipients.
• Uncontrolled hypertension (sitting systolic blood pressure remains \> 160 mmHg or diastolic blood pressure \> 100 mmHg after active antihypertensive treatment).
• There have been thrombotic events such as acute myocardial infarction, unstable angina pectoris, stroke, deep vein thrombosis or pulmonary embolism within the past six months.
• Those with known active malignant tumors or undergoing anti-tumor treatment (except for basal cell carcinoma, etc.) are excluded.
• Diseases affecting muscle metabolism and assessment:
• Severe thyroid dysfunction (uncontrolled).
• Diagnosed with chronic liver cirrhosis, acute exacerbation of chronic obstructive pulmonary disease (COPD), congestive heart failure (NYHA class IV), and other chronic diseases that seriously affect muscle metabolism.
• Due to severe limitations in limb movement caused by rheumatoid arthritis, Parkinson's disease, spinal cord injury, etc., it is impossible to complete muscle strength and functional tests.
• Long-term and excessive use of glucocorticoids (equivalent to prednisone \> 7.5 mg/day) or other drugs that may affect muscle metabolism (such as androgens).
• Other serious systemic diseases:
• Severe liver dysfunction (Child-Pugh grade C or ALT/AST \> 3 times the upper limit of normal).
• Active, uncontrolled severe infection.
• Life expectancy is less than one year.

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead

Related Publications (4)

• Sekar J, Attaway AH. The intersection of HIF-1alpha, O-GlcNAc, and skeletal muscle loss in chronic obstructive pulmonary disease. Glycobiology. 2023 Dec 25;33(11):873-878. doi: 10.1093/glycob/cwad081.

  PMID: 37812446 BACKGROUND

• Yin A, Fu W, Elengickal A, Kim J, Liu Y, Bigot A, Mamchaoui K, Call JA, Yin H. Chronic hypoxia impairs skeletal muscle repair via HIF-2alpha stabilization. J Cachexia Sarcopenia Muscle. 2024 Apr;15(2):631-645. doi: 10.1002/jcsm.13436. Epub 2024 Feb 9.

  PMID: 38333911 BACKGROUND

• Cirillo F, Mangiavini L, La Rocca P, Piccoli M, Ghiroldi A, Rota P, Tarantino A, Canciani B, Coviello S, Messina C, Ciconte G, Pappone C, Peretti GM, Anastasia L. Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1alpha. Int J Mol Sci. 2022 Jun 26;23(13):7114. doi: 10.3390/ijms23137114.

  PMID: 35806119 BACKGROUND

• Liu H, Li Y, Xiong J. The Role of Hypoxia-Inducible Factor-1 Alpha in Renal Disease. Molecules. 2022 Oct 28;27(21):7318. doi: 10.3390/molecules27217318.

  PMID: 36364144 BACKGROUND

MeSH Terms

Conditions

Sarcopenia; Anemia

Interventions

roxadustat

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: September 9, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): September 10, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 9, 2025

Record last verified: 2025-08