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DiabetesPhase 2NCT00381134

Improving Outcomes in Patients With Kidney Disease Due to Diabetes

A Phase 2 study testing losartan 100 mg orally once daily and spironolactone 25 mg orally once daily in people with Diabetes and Kidney Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 65 years
Conditions the study is for
Diabetes, Kidney Disease, Hypertension
What is being tested?
losartan 100 mg orally once daily and spironolactone 25 mg orally once daily
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
92 participants
Where
1 siteUnited States
Study dates
Jul 2003to Dec 2006
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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
Show all 23Show fewer
  • 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
  • AST or ALT greater than 2.5 the upper limit of normal for the laboratory
  • Pregnancy
  • History of autoimmune disease, connective tissue disease or multiple drug allergies
  • Anticipated need for renal replacement therapy within 12 months Inclusion criteria for normal subjects
  • Adult male and female subjects aged 20-65 of all ethnic backgrounds Exclusion criteria for normal subjects
  • Chronic medical conditions, including but not limited to diabetes mellitus, hypertension, chronic kidney disease, and hyperlipidemia.
  • Use of medications for antihypertensive
  • Inability to follow study protocol for any reason

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75230

Other trials in United States

About this study

Official title: Improving Outcomes in Diabetic Nephropathy

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

Read the detailed description

The long-range objective of this project is to prevent progression of diabetic nephropathy, the leading cause of end-stage renal disease (ESRD). In most patients diabetic nephropathy progresses inexorably to ESRD despite inhibition of the renin-angiotensin- aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). The specific aims of this proposal are to: 1) recruit a multiethnic cohort of 78 young adults (ages 20-40) with type 1 (n=36) or type 2 (n=36) diabetes and overt nephropathy (defined as a urine albumin/creatinine ratio > 300 mg albumin/g creatinine) and randomize in a double blind fashion to a control group consisting of ACEI-based therapy alone (ramipril 40 mg once daily) or one of two experimental groups: a) ACEI + ARB (ramipril 40 mg once daily plus losartan 100 mg once daily) or b) ACEI + mineralocorticoid receptor antagonist (MRA) (ramipril 40 mg once daily plus spironolactone 25 mg once daily); 2) conduct a 12-month prospective study to determine if proteinuria is reduced to a greater extent when either the ARB or MRA is added to ACEi-based therapy. This study is powered to detect a 30% greater reduction in 24-hour urine albumin/creatinine ratio in either experimental group versus control (alpha = 0.05, beta=0.10, repeated measures analysis of variance). Secondary endpoints to be examined include: (a) serum potassium and creatinine to assess safety, (b) TGF-beta, as a surrogate marker for ongoing renal injury, (c) plasma renin activity, angiotensin II and aldosterone levels and (d) plasma lipids and lipoprotein composition; and 3) perform repeated ambulatory blood pressure monitoring (ABPM) to examine the renoprotective effect of the 3 different regimens at comparable 24-hour BP of < 125/75 mmHg. The deliverables include: 1) documentation of the safety of maximal dose combination therapy; 2) the feasibility of utilizing 24-hr ABPM to establish BP independent renoprotective effects of specific antihypertensive therapies; and 3) provide preliminary data for future large-scale studies to test efficacy and safety of combining ACEi with MRA therapy on renal outcomes.

Being tested
losartan 100 mg orally once daily, spironolactone 25 mg orally once daily, placebo once orally once daily
Keywords
double-blind, placebo-controlled, nephropathy, blood pressure, urine albumin to creatinine ratio, placebo
Medical subject headings
Diabetes Mellitus, Kidney Diseases, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • losartan 100 mg orally once dailyDrug

  • spironolactone 25 mg orally once dailyDrug

  • placebo once orally once dailyDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (5)

  1. Changes in:

  2. urine transforming growth factor beta

  3. plasma lipids

  4. lipoprotein levels

  5. plasma aldosterone level

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2006 (estimated)
  2. Study startJul 2003
  3. Study completionDec 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00381134
Sponsor's protocol ID
DK063010-04 (completed)
Status last verified
Mar 2010
First submitted
26 Sep 2006
Last updated
2 Mar 2010
Results posted
No

Publications

  • 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.

    PubMed 38682786

  • 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.

    PubMed 36749631

  • 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.

    PubMed 33107592

  • 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.

    PubMed 27388615

  • 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.

    PubMed 24408116

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing losartan 100 mg orally once daily and spironolactone 25 mg orally once daily in people with Diabetes and Kidney Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in 24 hour urine albumin to creatinine ratio after 12 months of treatment. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00381134, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2010.

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