Improving Outcomes in Patients With Kidney Disease Due to Diabetes

NCT00381134 | Completed Phase 2

• 1 other identifier: DK063010-04 (completed)
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney disease affects about one out of three people with diabetes mellitus, a common medical problem. Treatment of kidney disease with medications that lower blood pressure can slow the kidney disease but there is no known cure. This study is designed to test the hypothesis that certain combination-based blood pressure lowering regimens (of FDA approved medications) are better than single agent-based regimens for lowering blood pressure and further slowing or preventing progression of this incurable disease

Conditions

Diabetes; Kidney Disease; Hypertension

Keywords

double-blind; placebo-controlled; nephropathy; blood pressure; urine albumin to creatinine ratio; placebo

Outcome Measures

Primary Outcomes (1)

• Change in 24 hour urine albumin to creatinine ratio after 12 months of treatment

Secondary Outcomes (5)

• Changes in:

• urine transforming growth factor beta

• plasma lipids

• lipoprotein levels

• plasma aldosterone level

Interventions

losartan 100 mg orally once daily DRUG

spironolactone 25 mg orally once daily DRUG

placebo once orally once daily DRUG

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male and female subjects aged 20-65 of all ethnic backgrounds.
• Type I diabetes mellitus defined as sudden onset of insulin requiring diabetes prior to age 20 and at least 5 years duration
• Type 2 diabetes mellitus defined as onset \> 20 years of age and treatment with oral hypoglycemic agent and/or insulin and increased C-peptide level.
• Seated SBP \> 130 mmHg documented at one screening visit or treated SBP \< 130 mmHg with a documented history of SBP \> 130 mmHg on more than one previous occasion
• Proteinuria defined as a 24-hour urine albumin/creatinine ratio \> 300 mg/g while on an ACE inhibitor with or without non-ARB, non-aldosterone antagonist treatment
• Ongoing treatment (\> 3 months) with an ACE inhibitor or ARB with or without additional antihypertensive therapy (e.g. CCB, a-blocker, b-blocker, clonidine).

You may not qualify if:

• BMI \> 45 kg/m2
• Baseline serum creatinine \> 3.0 mg/dl in females and \> 4.0 mg/dl in males or creatinine clearance \<20 ml/min estimated by Cockcroft-Gault equation (based on age, fasting serum creatinine concentration and ideal body weight in kilograms).
• Secondary cause of kidney disease other than diabetic nephropathy
• Serum potassium concentration \>5.5 mEq/L on ACE inhibitor therapy 7-10 days prior to randomization
• Poorly controlled diabetes, i.e. HgbA1C \> 11 mg/dl 7-10 days prior to randomization
• History of allergy to iothalamate or history of renal failure due to contrast nephropathy
• Stroke or myocardial infarction within the preceding 12 months prior to randomization
• Coronary revascularization procedure within past 6 months
• Clinically apparent congestive heart failure defined as clinical signs of heart failure or an ejection fraction of \< 40% (and/or depressed LV systolic function by echocardiogram).
• Terminal disease including cancer and AIDS
• Documented increase in serum creatinine \> 50% of baseline within 3 months prior to the run-in period
• Renal disease known or in the opinion of the investigator caused by a condition other than diabetes
• Known adverse reaction to study medications including ACE inhibitors, ARB and spironolactone
• History of chronic or intermittent gross hematuria
• Spontaneous 24-hour urine sodium excretion rate exceeding 350 mEq/day

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

The University of Texas Southwestern Medical Center

Dallas, Texas, 75230, United States

Location

Related Publications (5)

• Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2.

  PMID: 38682786 DERIVED

• Crompton M, Ferguson JK, Ramnath RD, Onions KL, Ogier AS, Gamez M, Down CJ, Skinner L, Wong KH, Dixon LK, Sutak J, Harper SJ, Pontrelli P, Gesualdo L, Heerspink HL, Toto RD, Welsh GI, Foster RR, Satchell SC, Butler MJ. Mineralocorticoid receptor antagonism in diabetes reduces albuminuria by preserving the glomerular endothelial glycocalyx. JCI Insight. 2023 Mar 8;8(5):e154164. doi: 10.1172/jci.insight.154164.

  PMID: 36749631 DERIVED

• Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.

  PMID: 33107592 DERIVED

• Srivastava A, Adams-Huet B, Vega GL, Toto RD. Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy. J Investig Med. 2016 Aug;64(6):1102-8. doi: 10.1136/jim-2016-000102. Epub 2016 Jul 7.

  PMID: 27388615 DERIVED

• Van Buren PN, Adams-Huet B, Nguyen M, Molina C, Toto RD. Potassium handling with dual renin-angiotensin system inhibition in diabetic nephropathy. Clin J Am Soc Nephrol. 2014 Feb;9(2):295-301. doi: 10.2215/CJN.07460713. Epub 2014 Jan 9.

  PMID: 24408116 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Kidney Diseases; Hypertension

Interventions

Losartan; Spironolactone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Robert D Toto, MD

  The University of Texas Southwestern Medical Center Dallas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 26, 2006
• First Posted: September 27, 2006
• Study Start: July 1, 2003
• Study Completion: December 1, 2006
• Last Updated: March 2, 2010

Record last verified: 2010-03

Locations

US (1)