- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06421870
Renoprotective Effects of Dapagliflozin Versus Pentoxiphylline in Chronic Kidney Disease Patients
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
It is only in recent years that the attention was drawn on the key role of the kidney in glucose homeostasis. Nevertheless, along with the liver, the kidney has a key role in ensuring the energy needs during fasting periods. This organ has a vital role in absorbing the entire quantity of the filtered glucose. Having a glomerular filtration rate of 180 litres per day, it filters approximately 180 grams of glucose per day, bringing its contribution in maintaining normal fasting plasma glucose (FPG) levels. (Cersosimo, E.et al 2014) The reabsorption of glucose is ensured by the sodium-glucose cotransporter (SGLT) 2, responsible for the reabsorption of 90% of glucose, and SGLT1, that reabsorbs the remaining glucose. (Mota, M., et al 2015) Glomerular hyperfiltration is a common pathway of kidney injury both in diabetic and non-diabetic settings and is associated with progression of kidney function decline. (Hoogeveen, E. K. 2022) Sodium-glucose co-transporter-2 (SGLT2) inhibitors are glucose-lowering agents that eliminate excess glucose through a glucosuric effect by reducing glucose reabsorption from the renal filtrate (Thomson, S. C., et al. 2019) It is indicated that the expression of high mobility group box 1 (HMGB1) increased in patients with kidney disease, and may result in renal injury through the activation of nuclear factor- κB (NF- κB) and an increase in receptor for advanced glycation end products (RAGE) expression. It is suggested that Dapagliflozin achieves its reno-protective status through its antioxidative stress and anti-inflammatory action via inhibition of the HMGB1 - RAGE - NF- κB signalling pathway. (Yao, D et al., 2018) SGLT2 is found almost exclusively in the luminal membranes of epithelial cells lining the first and second segments of the proximal tubules, where it mediates reabsorption of most (typically ≥ 90%) of filtered glucose. (Mudaliar S, et al. 2015) By inhibiting SGLT2 beneficial kidney effects are thought to be mediated by various mechanisms, including restoration of tubule-glomerular feedback leading to a reduction in intraglomerular pressure and hyperfiltration. Both conditions are considered core components of the pathophysiology contributing to progression of diabetic as well as nondiabetic CKD. Reductions in intraglomerular pressure, as shown by agents blocking the renin-angiotensin system, are frequently accompanied by a hemodynamic acute decrease in GFR, which is reversible after treatment cessation. (Wanner et al., 2018).
Common drug side effects of dapagliflozin include urinary tract infections, cystitis, hypotension, dehydration and female genital mycotic infections. Hypoglycemic episodes were reported in 6% to 10% of patients who administer dapagliflozin concurrently with insulin and insulin secretagogues. (Anderson SL et al., 2014) Pentoxifylline (PTF) is a synthetic dimethylxanthine derivative that modulates the rheological properties of blood and has both anti-oxidant and anti-inflammatory properties. PTF has been investigated for its possible use in diverse conditions, including osteoradionecrosis, diabetic kidney disease, and generally any condition associated with fibrosis. (Wen WX et al., 2017) PTF reduces levels of inflammatory markers: high-sensitivity C-reactive protein (hs-CRP), serum fibrinogen and TNF-α, this could reduce albuminuria and slow renal disease progression. (de Morales AM et al, 2019)
Thus, we need to evaluate the effect of Dapagliflozin versus Pentoxifylline on GFR among CKD non-diabetic patients.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Mohamed A Mohamed, MSc
- Phone Number: +20 1119090018
- Email: Mohammed.Ashraf@med.asu.edu.eg
Study Locations
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-
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Cairo, Egypt, 1181
- Recruiting
- Ain Shams University
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Contact:
- Mohamed A Mohamed, MSc
- Phone Number: +20 1119090018
- Email: Mohammed.Ashraf@med.asu.edu.eg
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- CKD stage 2 and 3
Exclusion Criteria:
- Diabetes mellitus
- History of recurrent or recent genitourinary infections
- Immunosuppressive medications
- Malignancy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Dapagliflozin arm
70 patients will take dapagliflozin 10 mg per day for 1 year in addition to standard management for chronic kidney disease
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Patients will be given dapagliflozin 10 mg once daily
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Active Comparator: Pentoxiphylline arm
70 patients will take pentoxifylline 400 mg twice daily for 1 year in addition to standard management for chronic kidney disease
|
Patients will be given pentoxyifylline 400 mg twice daily
|
No Intervention: Control
70 patients won't take either dapagliflozin or pentoxiphylline but they will continue their standard management for chronic kidney disease
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in estimated glomerular filtration rate
Time Frame: 1 year
|
eGFR will be based on serum creatinine and will be calculated by CKD-EPI 2021
|
1 year
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Change in proteinuria
Time Frame: 1 year
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Proteinuria quantification done by urine protein to creatinine ratio
|
1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Saeed A Saeed, Professor, Ain Shams University
Publications and helpful links
General Publications
- DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012 Jan;14(1):5-14. doi: 10.1111/j.1463-1326.2011.01511.x.
- Ni L, Yuan C, Chen G, Zhang C, Wu X. SGLT2i: beyond the glucose-lowering effect. Cardiovasc Diabetol. 2020 Jun 26;19(1):98. doi: 10.1186/s12933-020-01071-y.
- Nespoux J, Vallon V. Renal effects of SGLT2 inhibitors: an update. Curr Opin Nephrol Hypertens. 2020 Mar;29(2):190-198. doi: 10.1097/MNH.0000000000000584.
- Panchapakesan U, Pollock C. Drug repurposing in kidney disease. Kidney Int. 2018 Jul;94(1):40-48. doi: 10.1016/j.kint.2017.12.026. Epub 2018 Apr 6.
- Cersosimo E, Solis-Herrera C, Triplitt C. Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients. J Bras Nefrol. 2014 Jan-Mar;36(1):80-92. doi: 10.5935/0101-2800.20140014.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Urologic Diseases
- Disease Attributes
- Renal Insufficiency
- Chronic Disease
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Diseases
- Renal Insufficiency, Chronic
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Enzyme Inhibitors
- Platelet Aggregation Inhibitors
- Protective Agents
- Sodium-Glucose Transporter 2 Inhibitors
- Antioxidants
- Phosphodiesterase Inhibitors
- Free Radical Scavengers
- Radiation-Protective Agents
- Dapagliflozin
- Pentoxifylline
Other Study ID Numbers
- MD277/2023
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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