Effect of Bee Venom on Chronic Kidney Disease-Mineral Bone Disorders in Hemodialysis Patients: a Randomized Controlled Trial

Official title

Bee Venom As Immunomodulator and Its Effect on Chronic Kidney Disease-Mineral Bone Disorders in Hemodialysis Patients: a Prospective Randomized Controlled Trial

Overview

This study aims to evaluate the effectiveness of bee venom injections as a treatment for chronic kidney disease (CKD)-mineral bone disorder (MBD) in patients undergoing hemodialysis. MBD is a common complication in CKD patients, leading to abnormal mineral metabolism, bone disease, and increased cardiovascular risks. Current treatments are often inadequate and can have significant side effects. In this study, we will compare the effects of bee venom injections with standard care treatments in hemodialysis patients. Bee venom is known for its potential anti-inflammatory and immunomodulatory properties, which may help improve mineral metabolism and bone health regulation in these patients. By stimulating regulatory T cells (Tregs) through bee venom, we aim to reduce inflammation and restore bone health. We hope to answer whether bee venom can effectively reduce mineral bone disorder markers (such as calcium, phosphorus, and parathyroid hormone levels) and improve bone density in hemodialysis patients. The results could lead to a new treatment option for CKD-MBD, improving patient outcomes and quality of life.

Detailed description

This prospective, randomized controlled trial investigates the potential therapeutic role of bee venom in improving mineral bone disorder (MBD) among hemodialysis patients with chronic kidney disease (CKD). MBD is a common complication in CKD, characterized by disruptions in calcium, phosphorus, parathyroid hormone (PTH), and vitamin D metabolism, leading to abnormal bone remodeling and an increased risk of fractures and cardiovascular events. Conventional treatments for MBD, including phosphate binders, vitamin D analogs, and calcimimetics, often fall short in achieving optimal biochemical control and carry significant side effects. Therefore, there is a need for innovative therapies.

Bee venom, derived from the sting of the honeybee (Apis mellifera), has shown immunomodulatory and anti-inflammatory properties, which may play a role in modulating immune responses and regulating mineral metabolism. Previous studies suggest that bee venom can influence T cell activity, particularly enhancing the function of regulatory T cells (Tregs), which are known to suppress inflammation and help maintain immune balance. Given that inflammation is a key driver in the pathogenesis of MBD, targeting the immune system through bee venom presents a novel approach to improving bone and mineral metabolism.

The study will involve 60 patients undergoing maintenance hemodialysis, randomly assigned to either the intervention group receiving bee venom injections or the control group receiving standard care. Bee venom will be administered subcutaneously, with a dose escalation schedule starting at 0.05 mL three times weekly in the first week and increasing to 0.5 mL three times weekly by week 5. The treatment will last for six months.

Clinical and laboratory evaluations will assess the effects of bee venom on key MBD biomarkers, including serum calcium, phosphorus, PTH levels, and bone turnover markers. Radiological assessments using quantitative computed tomography (QCT) will evaluate bone mineral density changes at the lumbar vertebrae. The study will also assess the safety profile of bee venom by monitoring adverse events and allergic reactions.

The primary goal is determining whether bee venom can significantly improve MBD markers compared to standard care. Secondary objectives include evaluating changes in bone mineral density, assessing the safety and tolerability of bee venom, and exploring potential effects on inflammation markers and cardiovascular risk factors. The findings from this study may provide insights into the possible role of bee venom as a therapeutic agent in managing CKD-MBD. They could lead to a new treatment option for hemodialysis patients.

Interventions

• Drug Bee Venom Injection
  This intervention involves the administration of purified bee venom from Apis mellifera species (Abevac) via subcutaneous injections. The dosage starts at 0.05 mL three times a week and gradually escalates to 0.5 mL three times a week by week 5. The total duration of the treatment is 6 months. Bee venom is being evaluated for its potential immunomodulatory effects, including enhancing regulatory T cell function and improving mineral bone disorder (MBD) in patients undergoing hemodialysis.
• Drug Standard Care for CKD-MBD
  This intervention represents the standard care for patients with chronic kidney disease-mineral bone disorder (CKD-MBD) undergoing hemodialysis. The treatment typically includes phosphate binders to control phosphorus levels, vitamin D receptor activators to regulate calcium and phosphorus metabolism, and calcimimetics to control parathyroid hormone (PTH) levels. The specific regimen may vary according to individual patient needs, but the control group will not receive bee venom injections as pa

Primary outcome measures

• Improvement in Bone-Specific Biomarkers (BALP, P1NP, TRAP-5b) [Time frame: 6 months The primary outcome will be assessed at baseline and after 6 months of treatment to evaluate the effect of bee venom on bone metabolism in CKD-MBD patients undergoing hemodialysis.]

Secondary outcome measures (1)

• Change in Bone Mineral Density (BMD) Measured by QCT of Lumbar Vertebrae [Time frame: 6 months Bone mineral density measurements will be taken at baseline and at the end of the 6-month treatment period to assess the impact of bee venom on bone health in CKD-MBD patients undergoing hemodialysis.]

Eligibility criteria

Inclusion criteria

• Patients of both sexes aged 18 years and older.
• Patients undergoing maintenance hemodialysis three times weekly for at least six months.
• Patients who are not scheduled for kidney transplantation within the next year.

Exclusion criteria

• Current pregnancy or lactation.
• Medical history of chronic conditions such as liver disease, cancer, or autoimmune diseases.
• Refusal to participate in the study.
• Active chronic infections, including HIV, HCV, HBV, and tuberculosis.
• Current use of medications affecting bone metabolism (e.g., calcitonin, denosumab, estrogen) within the last six months.
• History of renal allograft failure within the past year.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Urology and Nephrology Center, Mansoura University — Al Mansurah

Publications

• Waziri B, Duarte R, Naicker S. Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Current Perspectives. Int J Nephrol Renovasc Dis. 2019 Dec 24;12:263-276. doi: 10.2147/IJNRD.S191156. eCollection 2019. PMID 31920363
• An HJ, Kim JY, Kim WH, Han SM, Park KK. The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction. Molecules. 2016 Aug 27;21(9):1137. doi: 10.3390/molecules21091137. PMID 27618890
• Hwang DS, Kim SK, Bae H. Therapeutic Effects of Bee Venom on Immunological and Neurological Diseases. Toxins (Basel). 2015 Jun 29;7(7):2413-21. doi: 10.3390/toxins7072413. PMID 26131770
• Carpena M, Nunez-Estevez B, Soria-Lopez A, Simal-Gandara J. Bee Venom: An Updating Review of Its Bioactive Molecules and Its Health Applications. Nutrients. 2020 Oct 31;12(11):3360. doi: 10.3390/nu12113360. PMID 33142794

Identifiers

NCT: NCT06901102 · MS.24.12.3035

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗