Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05487755
Other study ID # DN mangement
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date February 1, 2022
Est. completion date September 1, 2023

Study information

Verified date May 2024
Source Tanta University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The objective of this study is to investigate and compare the safety and efficacy of selective (PDE5) enzyme inhibitor; tadalafil and non selective (PDE) inhibitor; pentoxifylline in diabetic nephropathy to improve glucose metabolism, lipid profile and decrease albuminuria.


Description:

Diabetic nephropathy(DN) is one of the major micro- vascular complications of diabetes mellitus and the leading cause of end-stage renal disease (ESRD) that require renal replacement therapies. The average incidence of diabetic nephropathy is 3% per year during the first 10 to 20 years after diabetes onset. Diabetic nephropathy occurs in 20-40% of all diabetic patients. Pathogenesis of diabetic nephropathy is complex and multi-factorial in which diabetes mellitus has more than pathway for initiation and progression of the disease. - Metabolic pathway: result in formation of advanced glycation end products (AGEs). - Inflammatory pathway: result in increase serum level of tumor necrosis factor-α(TNF . - Hemodynamic pathway: result in increase serum level of endothelin-1 which result in glomerular hypertension and hyper filtration. Tadalafil is a phosphodiesterase type 5 enzyme (PDE5) inhibitor used mainly in erectile dysfunction and pulmonary hypertension by a mechanism involving increase(NO-cGMP-PKG) signaling pathway. Tadalafil is a powerful pleiotropic drug that it can be used in DN as it can target more than pathway involved in pathogenesis of DN include hyperglycemia and endothelial dysfunction through increase (NO-cGMP) signaling pathway as well as hyperlipidemia. Animal studies reported that tadalafil increase significantly total antioxidant capacity(TAC),decrease significantly serum level of inflammatory marker (TNF- α), blood glucose level, serum creatinine ,serum urea and urinary albumin excretion all result in decrease renal inflammation, injury, necrosis and apoptosis. Pentoxifylline is a methyl xanthine derivative, non selective phosphodiesterase enzyme inhibitor used mainly to treat peripheral vascular diseases by improve blood flow, increase red blood cell flexibility and inhibit platelet aggregation. Pentoxifylline have been recently widely used in many animal studies and clinical trials to evaluate its efficacy in management of DN and the results were so promising.(14) Pentoxifylline can slow the decrease in eGFR, and significantly reduce albuminuria in which it can be effective alternative to ACEI in reducing albuminuria as proved by clinical trial.(15) The powerful effect of pentoxifylline in DN as it can affect several pathways implicated in pathogenesis of DN; it has hypoglycemic effect by decrease Significantly blood glucose, HbA1c and serum triglyceride, it also decrease pro inflammatory cytokines (TNF-α, IL-1, IL-6), reduce plasma level of malondialdehyde and increase glutathione level.(16) Neutrophil Gelatinase-Associated Lipocalin (NGAL): is a 25-kDa protein belong to lipocalin superfamily. The urinary concentration of NGAL increase in renal tubular damage as a result of both diminished reabsorption and increased release from renal tubules into urine indicating both proximal and distal tubular damage respectively.(17) NGAL is not considered a marker of renal function but a marker of structural damage of renal tubules, its level can quantify the degree of tubular damage.(18) NGAL can be used as a precocious marker of therapeutic response by application of NGAL measurement in monitoring the effectiveness of a particular treatment and predicting different clinical outcomes in the course of renal diseases


Recruitment information / eligibility

Status Completed
Enrollment 90
Est. completion date September 1, 2023
Est. primary completion date March 1, 2023
Accepts healthy volunteers No
Gender All
Age group 35 Years to 70 Years
Eligibility Inclusion Criteria: - A confirmed with clinical diagnosis of T2DM with duration at least 7 years to ensure established of micro-vascular complication (DKD). - females (post-menopause), males with sufficient erectile function. - Patients on stage 3 DN with evidence of persistent micro-albuminuria. All Abnormal tests of (UACR) must be confirmed in two out of three samples collected over a 6 month period before enrolled in the study. - (urinary ACR=30-300mg/g) in 3 consecutive measurements in 6 months period despite treatment with RAAS blockade(ramipril 10 mg ) ACEI or for at least 6 months period before enrollment in the study at maximum recommended tolerated dose. Exclusion Criteria:Cardiovascular disease: angina, arrhythmias, myocardial Infarction, heart failure (NYHA II -IV), uncontrolled hypertension > (170 \100 mm Hg) severe hypotension < (90\50 mm Hg), Hearing problem, vision defect, previous episodes of retinal / cerebral hemorrhage, psychiatric disease, thyroid disorders, alcohol abuse, smoking, Hepatic insufficiency (child -Pugh class C), (ALT or AST>3N), cholestasis, history of chronic inflammatory, immunologic or malignant disease. Acute inflammation or infectious disease in the previous 3 months, taking immunosuppressive treatment, Known allergy to tadalafil or methylxanthine, Use alpha one blockers, use of anti-oxidant drugs three months before enrollment in the study ,medications strongly alter CYP3A4 inducer or inhibitor, use of nitrates, other PDEI drugs, - Renal disease (acute kidney injury, recent exposure to radio- contrast media, creatinine clearance <30 ml/ min /1.73 m2 , bleeding disorders, peptic ulcer, and stroke, Pregnancy, lactation.

Study Design


Intervention

Drug:
Tadalafil 20Mg Oral Tablet
Tadalafil is a phosphodiesterase type 5 enzyme (PDE5) inhibitor used mainly in erectile dysfunction and pulmonary hypertension by a mechanism involving increase(NO-cGMP-PKG) signaling pathway.(8) Tadalafil is a powerful pleiotropic drug that it can be used in DN as it can target more than pathway involved in pathogenesis of DN include hyperglycemia and endothelial dysfunction through increase (NO-cGMP) signaling pathway as well as hyperlipidemia
Pentoxifylline 400 MG Oral Tablet
Pentoxifylline is a methyl xanthine derivative, non selective phosphodiesterase enzyme inhibitor used mainly to treat peripheral vascular diseases by improve blood flow

Locations

Country Name City State
Egypt Faculty of pharmacy Tanta

Sponsors (1)

Lead Sponsor Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

References & Publications (2)

Rivero A, Mora C, Muros M, Garcia J, Herrera H, Navarro-Gonzalez JF. Pathogenic perspectives for the role of inflammation in diabetic nephropathy. Clin Sci (Lond). 2009 Mar;116(6):479-92. doi: 10.1042/CS20080394. — View Citation

Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond). 2013 Feb;124(3):139-52. doi: 10.1042/CS20120198. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change in Urinary albumin/creatinine ratio (ACR) Measurement of urine albumin to creatinne ratio by measurement of urine albumin using Turbidimetric immunoassay method and measurement of urine creatinnie by standard by enzymatic colorimetric methods Change between baseline and six months after
Primary Change in Hemoglobin A1c (HbA1c). Measurement of Hemoglobin A1C using (HPLC: ion exchange chromatography) Change between baseline and six months after
Primary Change in Fasting blood glucose. Measurement of Fasting blood glucose by using standard enzymatic colorimetric methods Change between baseline and six months after
Primary Change in Sr Cr Measurement of serum creatinine using colorimetric technique Change between baseline and six months after
Primary Change in Creatinine clearance Creatinine clearance was calculated by (Cockcroft-Gault Formula) Change between baseline and six months after
Primary change in 2- Hours Postprandial blood glucose Measurement 2- Hours Postprandial blood glucose in blood using standard enzymatic colorimetric methods Change between baseline and six months after
Secondary Change in serum ((TNF-a). Measurement of serum level of (TNF-a) by Enzyme linked immunosorbent assay (ELISA). Change between baseline and six months after
Secondary Change in Urinary NGAL (uNGAL). Measurement of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL)using by Enzyme linked immunosorbent assay ELISA technique: Change between baseline and six months after
Secondary Change in Lipid profile (TG, LDL, and HDL). Measurement of serum lipid profile (TC,TG,HDL,LDL)using Enzymatic Colorimetric Method Change between baseline and six months after
Secondary Change in serum malondialdehyde (MDA) . Meaurement of serum malondialdehyde by Enzyme linked immunosorbent assay (ELISA) . Change between baseline and six months after
See also
  Status Clinical Trial Phase
Terminated NCT03840343 - Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease Phase 1
Completed NCT04549324 - Sleep Apnea, Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy
Recruiting NCT03502031 - Safety and Efficacy of Two Year of RAAS Alone or in Combination With Spironolactone Therapy Phase 4
Completed NCT03681704 - the Integrated Traditional Chinese and Western Medicine Treat Early Stage DKD Phase 1
Completed NCT03681249 - the Integrated Traditional Chinese and Western Medicine Treat Middle Stage DKD Early Phase 1
Withdrawn NCT03504566 - Rotation for Optimal Targeting of Albuminuria and Treatment Evaluation (ROTATE-2) Phase 4
Completed NCT03889236 - Dietary Interventions on Glycocalyx Dimensions in South Asian Patients With Diabetic Nephropathy. N/A
Completed NCT06326034 - Impact of Dapagliflozin as Add-on Therapy on Glycemic Status and Quality of Life in Type 2 Diabetic Patients Phase 4
Recruiting NCT04931537 - Screening and Application Research of Early Diabetic Nephropathy Markers Based on Lipidomics.
Not yet recruiting NCT05373004 - Comparison Between the Efficacy of SGLT2 Inhibitor Therapy Versus ACE Inhibitor in the Treatment of Diabetic Kidney Disease Phase 2/Phase 3
Recruiting NCT03622762 - Green Tea Extract on Soluble RAGE in Patients With Diabetic Nephropathy Phase 2
Recruiting NCT03445247 - Extracorporeal Low-intensity Shockwave in Diabetic Nephropathy N/A
Not yet recruiting NCT06068439 - Study of the Protective Effect of Low-dose Aspirin on Renal Function in Patients With Early Diabetic Nephropathy Phase 2/Phase 3
Recruiting NCT04143412 - Efficacy of ACE Inhibitors, MRAs and ACE Inhibitor/ MRA Combination Phase 2
Not yet recruiting NCT06222476 - Effect of Dorzagliatin on Renal Function Outcomes in People With Type 2 Diabetes: a Multicentric, Prospective, Randomized Study. N/A
Active, not recruiting NCT04573920 - Atrasentan in Patients With Proteinuric Glomerular Diseases Phase 2
Recruiting NCT05888909 - Multidimensional Accurate Diagnosis and Treatment Technology and Clinical Transformation of Type 2 Diabetes Nephropathy
Not yet recruiting NCT04962399 - Relationship Between Serum N/OFQ and Type 2 Diabetic Nephropathy
Not yet recruiting NCT03591939 - T-regulatory Cells in Diabetic Type Two Nephropathy
Active, not recruiting NCT03859817 - Observational Study to Evaluate the Relationship Between Ketonemia and Renal Function in the Diabetic Patient