The Use of Cilostazol in Patients With Diabetic Nephropathy
Condition: Diabetes Mellitus, Type 2; Diabetes Complications
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Complications
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients with type 2 diabetes have a long duration of disease for the development of
      complications. Among all complications, microangiopathic complications are major causes of
      mortality and morbidity in diabetic patients. In Asia, patients with type 2 diabetes are
      particularly susceptible to the development of kidney disease. Patients with diabetic kidney
      disease have more adverse metabolic profiles and increased risk of having other complications
      such as blindness, stroke, heart attack and nerve damage than those without. Despite
      receiving the best of care, the combined event rate of death, cardiovascular disease and end
      stage kidney disease in diabetic patients with renal impairment remained as high as 10% per
      year.

      Cilostazol reduces platelet aggregation and prevents formation of blood clots. Furthermore,
      cilostazol treatment has been shown to reduce serum triglyceride concentrations and increase
      HDL-cholesterol levels. In this randomized placebo-controlled, double-blinded study, the
      investigators hypothesize that Cilostazol may reduce the rate of decline in renal function in
      Chinese patients with type 2 diabetes and mild to moderate renal impairment. Sixty patients
      will be randomised to receive either Cilostazol 100 mg twice daily or placebo for 12 months.
      The effect of Cilostazol on the progression of diabetic nephropathy, as defined by rates of
      decline in glomerular filtration rate, serum creatinine and urinary albumin excretion rate
      will be measured. The results will provide additional insight on the management of diabetic
      kidney disease which is prevalent among Chinese diabetic patients in Hong Kong.
    

Detailed description: 
      Hypothesis:

      Cilostazol reduces the rate of decline in renal function in Chinese patients with type 2
      diabetes and mild to moderate renal impairment secondary to diabetic nephropathy.

      Objectives:

      To assess the suppressive effect of Cilostazol on the progression of diabetic nephropathy, as
      defined by rates of decline in glomerular filtration rate, serum creatinine and urinary
      albumin excretion rate.

      The rising prevalence of diabetes in Asia imposes a heavy burden on the health care system.
      Given the increasingly early onset of disease, patients with type 2 diabetes have long
      duration of disease for the development of complications. Among all complications,
      microangiopathic complications are major causes of mortality and morbidity in diabetic
      patients. In Asia, patients with type 2 diabetes are particularly susceptible to the
      development of nephropathy. Among dialysis patients, the primary disease is diabetic
      nephropathy in about 40 to 50 % of patients. Despite the inhibition of the renin angiotensin
      system using either ACE inhibitor or AII receptor blocker (ARB) as well as introduction of
      tight glycaemic and blood pressure control, the prevalence of diabetic nephropathy remains
      high. More importantly, patients with nephropathy have more adverse metabolic profiles and
      increased risk of having other complications such as retinopathy, macrovascular diseases and
      neuropathy than those without. Indeed, according to the RENAAL Study, despite receiving the
      best of care, the combined event rate of death, cardiovascular disease and end stage renal
      disease in diabetic patients with renal impairment remained as high as 10% per year.

      Cilostazol exerts antiplatelet, antithrombotic and vasodilating effects by inhibiting
      phosphodiesterase type 3 in platelets and vascular smooth muscle cells. Furthermore,
      cilostazol treatment has been shown to reduce serum triglyceride concentrations and increase
      HDL-cholesterol levels. In Japanese patients with type 2 diabetes, cilostazol therapy was
      associated with regression of carotid intimal media thickness and could prevent the onset of
      silent brain infarction. On the other hand, abnormal metabolism of prostaglandins in renal
      glomeruli has been postulated to modulate renal haemodynamics. Elevated levels of
      platelet-derived microparticles and soluble adhesion molecules may further contribute to the
      development of diabetic nephropathy. Cilostazol treatment had been shown to reduce serum
      levels of PMP, activated platelet subsets, soluble adhesion molecules and urinary excretion
      of thromboxane B2 in patients with type 2 diabetes. These changes were accompanied by a
      reduction in urinary albumin excretion and an increase in creatinine clearance.
    

Intervention name(s): Cilostazol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Cilostazol 100 mg twice daily; 1 tablet twice daily
Other intervention name(s): Pletaal
Intervention MeSH terms: Cilostazol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Diabetic nephropathy; Macroalbuminuria; Pletaal