Efficacy of ACE Inhibitors, MRAs and ACE Inhibitor/ MRA Combination

Diabetic Nephropathy Type 2 Clinical Trial

Official title:

Antiproteinuric Efficacy of ACE Inhibitors, Selective MRAs and ACE Inhibitor/Selective MRA Combination Therapy in Diabetic Hypertensives With Microalbuminuria

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04143412
• Other study ID #: RAAS blockers in albuminuria
• Status: Recruiting
• Phase: Phase 2
• Start date: February 4, 2019
• Est. completion date: March 2020

Study information

• Verified date: January 2020
• Source: Beni-Suef University
• Contact: Mostafa O El Mokadem, M.D.
• Phone: +201009414408
• Email: mostafa.elmokadem9[@]med.bsu.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of our work is to compare the antiproteinuric efficacy of ACEI monotherapy, Selective MRA monotherapy and their combination in mildly hypertensive patients with type 2 diabetes mellitus and microalbuminuria

Description:

Diabetic nephropathy (DN) is the most common cause renal failure in Western countries, responsible for 45% of patients on renal replacement therapy.Diabetic nephropathy was characterized in the early stage by increased albumin excretion in urine, known as microalbuminuria. (DN) results from interactions between different pathological factors that include hyperglycemia, increased activity of the renin-angiotensin-aldosterone-system (RAAS), uncontrolled high systemic and glomerular pressure . (DN) optimal therapy continues to evolve. The main lines of treatment include strict glycemic and blood pressure (BP) control. The angiotensin converting enzyme (ACE) inhibitors have been known to reduce proteinuria both in normotensive and hypertensive patients with diabetic nephropathy and in hypertensive individuals with end stage renal failure . The mechanism by which ACE inhibitors exert their effect on proteinuria reduction is still unknown. The control of high systemic arterial pressure can be beneficial by reducing the filtration pressure. However, no association has been found between antihypertensive effect and proteinuria reduction in several studies. Microalbuminuria which is an early sign of nephropathy can be decreased also by use of Angiotensin receptor blockers (ARBs) in patients with type 2 diabetes mellitus . Insufficient blockade of aldosterone may lead to inadequate anti-albuminuric effects. Studies show that renin-angiotensin-aldosterone system inhibition with ACEI/ARB alone sometimes does not achieve optimal renoprotective effects and does not reduce progression of renal disease, despite therapy. Addition of mineralocorticoid receptor antagonists (MRAs) to angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy was found to reduce proteinuria in patients diabetic nephropathy and can delay progression of renal dysfunction.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: March 2020
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• Adult male and non-pregnant female patients with established diagnosis of type 2 DM at least five years ago with glycosylated hemoglobin (HbA1c) = 8.5%

• Age 30-80 Y

• Stage 1 hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) and microalbuminuria diagnosed by measuring Urinary albumin/creatinine ratio (UACR) . Microalbuminuria was defined at a level between (30-300 mg/g)

• Patients included in our study had never been treated with ACEIs, ARBs or aldosterone antagonists, serum potassium level = 3.5 and = 5.0 mmol/L before randomization with estimated glomerular filtration rate (e GFR) =50 mL/min/1.73 m2

Exclusion Criteria:

• Patients with type 1 diabetes mellitus

• Patients with BP = 160/100 mmHg

• Patients with secondary hypertension

• Non-diabetic nephropathy including (chronic glomerulonephritis, polycystic kidney disease and nephrosclerosis),

• Confirmed bilateral renal artery stenosis or stenosis of the renal artery in solitary functioning kidney

• History of New York Heart Association functional class III and IV heart failure

• Patients with rapid progression of kidney disease and women who were pregnant, breast-feeding, or planning to become pregnant during the study period

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy Type 2
• Kidney Diseases
• Microalbuminuria Due to Type 2 Diabetes Mellitus

Intervention

Drug:
• Tritace (Ramipril 10 mg)
Stratified randomized clinical trial

Locations

Country	Name	City	State
Egypt	Faculty of Medicine,Beni-Suef University	Bani Suwayf

Sponsors (1)

Lead Sponsor	Collaborator
Beni-Suef University

Country where clinical trial is conducted

Egypt, 

References & Publications (8)

Cagnoni F, Njwe CA, Zaninelli A, Ricci AR, Daffra D, D'Ospina A, Preti P, Destro M. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination. Vasc Health Risk Manag. 2010 Aug 9;6:549-59. Review. — View Citation

Cao Z, Cooper ME. Pathogenesis of diabetic nephropathy. J Diabetes Investig. 2011 Aug 2;2(4):243-7. doi: 10.1111/j.2040-1124.2011.00131.x. Review. — View Citation

Cooper LB, Lippmann SJ, Greiner MA, Sharma A, Kelly JP, Fonarow GC, Yancy CW, Heidenreich PA, Hernandez AF. Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease. J Am Heart Assoc. 2017 Dec 23;6(12). pii: e006540. doi: 10.1161/JAHA.117.006540. — View Citation

Espinel E, Agraz I, Ibernon M, Ramos N, Fort J, Serón D. Renal Biopsy in Type 2 Diabetic Patients. J Clin Med. 2015 May 18;4(5):998-1009. doi: 10.3390/jcm4050998. Review. — View Citation

Galle J. Reduction of proteinuria with angiotensin receptor blockers. Nat Clin Pract Cardiovasc Med. 2008 Jul;5 Suppl 1:S36-43. doi: 10.1038/ncpcardio0806. Review. — View Citation

Jalal S, Sofi FA, Abass SM, Alai MS, Bhat MA, Rather HA, Lone NA, Siddiqi MA. Effect of amlodipine and lisinopril on microalbuminuria in patients with essential hypertension: A prospective study. Indian J Nephrol. 2010 Jan;20(1):15-20. doi: 10.4103/0971-4065.62090. — View Citation

Satirapoj B, Adler SG. Prevalence and Management of Diabetic Nephropathy in Western Countries. Kidney Dis (Basel). 2015 May;1(1):61-70. doi: 10.1159/000382028. Epub 2015 May 1. Review. — View Citation

Zelmanovitz T, Gerchman F, Balthazar AP, Thomazelli FC, Matos JD, Canani LH. Diabetic nephropathy. Diabetol Metab Syndr. 2009 Sep 21;1(1):10. doi: 10.1186/1758-5996-1-10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary albumin/creatinin ratio (UACR)	Percentage change in albumin/creatinin ratio compared with the baseline value	24 weeks
Secondary	Blood pressure	change in blood pressure level	24 weeks
Secondary	estimated Glomerular Filtration Rate (e GFR)	change in estimated Glomerular Filtration Rate (e GFR)	24 weeks
Secondary	Serum K	change in serum K level	24 weeks