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Diabetic NephropathyPhase 3NCT00340678

Renoprotection in Early Diabetic Nephropathy in Pima Indians

A Phase 3 study testing Losartan in people with Diabetic Nephropathy, 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

This investigation is a randomized, double-blinded, placebo-controlled clinical trial in adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine ration less than 30 mg/g) or microalbuminuria (albumin-to-creatinine ration = 30-299 mg/g) to test the hypothesis that blockade of the… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Diabetic Nephropathy
What is being tested?
Losartan
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
170 participants
Where
1 siteUnited States
Study dates
Aug 1995to Mar 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • Volunteers from the Gila River Indian Community who meet the eligibility criteria will be invited to participate.
  • To be eligible for participation in the study, subjects must meet the following criteria:
  • Aged 18-65.
  • Diagnosis of type 2 diabetes greater than or equal to 5 years.
  • Serum creatinine concentration less than to 1.4 mg/dl.
  • Serum potassium concentration less than or equal to 5.5 milliequivalents (mEq)/L.
  • At least 2 of 3 weekly screening urinary albumin-to-creatinine ratios less than 300 mg/g. All screening tests are to be within 3 months of enrollment.
  • Willingness, after receiving a thorough explanation of the study, to participate.

Who cannot join

  • Subjects will be excluded for the following reasons:
  • Clinically significant disorders of the liver, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, pulmonary diseases, renal-urinary disorders, gastrointestinal disorders, or hematocrit levels less than or equal to 30 percent in women or less than or equal to 35 percent in men.
  • Renovascular or malignant hypertension; uncontrolled hypertension despite treatment with three antihypertensive drugs; or hypertension that is being treated with antihypertensive medicines and the primary care physician or the patient refuses to adopt the blood pressure treatment regimen outlined in the study protocol.
  • Hematuria of unknown etiology.
  • Chronic debilitating disorders with or without treatment that would interfere with the assessment of kidney function or that might reduce the chances of survival for a sufficient length of time to evaluate efficacy of treatment.
  • Currently receiving a drug regimen that includes: steroids, immunosuppressants, or investigational new drugs.
Show all 13Show fewer
  • Pregnancy. Women of childbearing potential must have a negative pregnancy test prior to entry and every three months during the study.
  • Evidence of inability to empty the bladder.
  • Hypersensitivity to angiotensin-converting enzyme inhibitors (ACEi), ARBs, or iodine.
  • Bleeding disorders, since kidney biopsies could not be performed safely in these individuals.
  • Massive obesity with body mass index greater than or equal to 45 kg/m(2).
  • Non-diabetic renal disease.
  • Conditions that are likely to interfere with informed consent or compliance with the protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • NIDDK, Phoenix

    Phoenix, Arizona, 85014

Other trials in United States

About this study

This investigation is a randomized, double-blinded, placebo-controlled clinical trial in adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine ration less than 30 mg/g) or microalbuminuria (albumin-to-creatinine ration = 30-299 mg/g) to test the hypothesis that blockade of the renin-angiotensin system with the angiotensin receptor blocker (ARB) losartan can prevent or further attenuate the development and progression of early diabetic nephropathy in subjects with type 2 diabetes mellitus who are receiving standard diabetes care.

One hundred seventy subjects were recruited for the study, all of whom had type 2 diabetes for at least 5 years, serum creatinine concentrations less than 1.4 mg/dl, and no evidence of non-diabetic renal diseases. Ninety-two of the subjects had normal urinary albumin excretion at baseline and other 78 had microalbuminuria. Subjects in each albumin excretion group were randomized to treatment with either the angiotensin II receptor antagonist, losartan, or placebo. Measurements of glomerular filtration rate (GFR), renal plasma flow (RPF) and fractional clearances of albumin and IgG will be made initially, at one month, and at 12-month intervals from baseline thereafter. A kidney biopsy was performed after six years in 111 subjects. Morphometric analysis of renal biopsies was used to determine differences in glomerular structure between treatment groups.

Read the detailed description

This investigation is a randomized, double-blinded, placebo-controlled clinical trial in adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine ratio < 30 mg/g) or microalbuminuria (albumin-to-creatinine ratio = 30-299 mg/g) to test the hypothesis that blockade of the renin-angiotensin system with the angiotensin receptor blocker (ARB) losartan can prevent or further attenuate the development and progression of early diabetic nephropathy in subjects with type 2 diabetes mellitus who are receiving standard diabetes care.

One hundred seventy subjects were recruited for the study, all of whom had type 2 diabetes for at least 5 years, serum creatinine concentrations < 1.4 mg/dl, and no evidence of non-diabetic renal diseases. Ninety-two of the subjects had normal urinary albumin excretion at baseline and the other 78 had microalbuminuria. Subjects in each albumin excretion group were randomized to treatment with either the angiotensin II receptor antagonist, losartan, or placebo. Measurements of glomerular filtration rate (GFR), renal plasma flow (RPF) and fractional clearances of albumin and immunoglobulin G (IgG) were made initially, at one month, and at 12-month intervals from baseline thereafter. A kidney biopsy was be performed after six years in 111 subjects. Morphometric analysis of renal biopsies was used to determine differences in glomerular structure between treatment groups.

The major outcome measure was a decline in GFR to less than or equal to 60 ml/min or to half the baseline value in subjects that enter the study with a GFR of < 120 ml/min. Other measures of renoprotection were assessed, including group differences in 1) change in albumin excretion, 2) change in serum creatinine concentration, and 3) glomerular morphology in all subjects as outlined above.

Being tested
Losartan, Placebo
Keywords
Angiotensin II Receptor Antagonist, Therapeutic Trial, Glomerular Filtration Rate, Kidney Biopsy, Non-Insulin Dependent Diabetes Mellitus
Medical subject headings
Diabetic Nephropathies, Diabetes Mellitus, Type 2

What participants receive

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

  • LosartanDrug

    Also called Cozaar, MK-954, DuP 753

    Treatment with losartan began at 50 mg daily, with the dose increasing to 100 mg daily after 1 week if symptomatic hypotension did not develop.

  • PlaceboDrug

    Treatment with placebo corresponding to each dose of losartan.

Study groups in NCT00340678
Study groupRoleWhat they receive
Normoalbuminuria LosartanExperimentalSubjects with normal urinary albumin excretion were treated with losartan began at 50 mg daily, with the dose increasing to 100 mg daily after 1 week if symptomatic hypotension did not develop.
Receives: Drug: Losartan
Normoalbuminuria PlaceboPlacebo comparatorSubjects with normal urinary albumin excretion were treated with placebo corresponding to each dose of losartan.
Receives: Drug: Placebo
Microalbuminuria LosartanExperimentalSubjects with microalbuminuria were treated with losartan began at 50 mg daily, with the dose increasing to 100 mg daily after 1 week if symptomatic hypotension did not develop.
Receives: Drug: Losartan
Microalbuminuria PlaceboPlacebo comparatorSubjects with Microalbuminuria were treated with placebo corresponding to each dose of losartan.
Receives: Drug: Placebo

What is being measured

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

  1. Number of Participants With Decline in GFR

    Participants were monitored for up to 6 years. This is the number of participants who had a decline in GFR to less than or equal to 60 ml/min or to half the baseline value in subjects that enter the study with a GFR of less than 120 ml/min during the time of observation.

    Measured: Up to 6 years

Secondary outcomes (1)
  1. Glomerular Volume

    Measured: 6 years after first treatment

Timeline

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

  1. First posted21 Jun 2006 (estimated)
  2. Study startAug 1995
  3. Primary completionMay 2012
  4. Study completionMar 2014

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
170 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00340678
Sponsor's protocol ID
999995037
Other IDs
OH95-DK-N037
Status last verified
Oct 2013
First submitted
19 Jun 2006
Last updated
25 Mar 2021
Data monitoring committee
Yes

Publications

  • Zatz R, Meyer TW, Rennke HG, Brenner BM. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5963-7. doi: 10.1073/pnas.82.17.5963.

    PubMed 3862110
  • Zatz R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986 Jun;77(6):1925-30. doi: 10.1172/JCI112521.

    PubMed 3011862
  • Anderson S, Rennke HG, Garcia DL, Brenner BM. Short and long term effects of antihypertensive therapy in the diabetic rat. Kidney Int. 1989 Oct;36(4):526-36. doi: 10.1038/ki.1989.227.

    PubMed 2681929
  • Weil EJ, Fufaa G, Jones LI, Lovato T, Lemley KV, Hanson RL, Knowler WC, Bennett PH, Yee B, Myers BD, Nelson RG. Effect of losartan on prevention and progression of early diabetic nephropathy in American Indians with type 2 diabetes. Diabetes. 2013 Sep;62(9):3224-31. doi: 10.2337/db12-1512. Epub 2013 Apr 1.

    PubMed 23545707
  • 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
  • Fort PE, Rajendiran TM, Soni T, Byun J, Shan Y, Looker HC, Nelson RG, Kretzler M, Michailidis G, Roger JE, Gardner TW, Abcouwer SF, Pennathur S, Afshinnia F. Diminished retinal complex lipid synthesis and impaired fatty acid beta-oxidation associated with human diabetic retinopathy. JCI Insight. 2021 Oct 8;6(19):e152109. doi: 10.1172/jci.insight.152109.

    PubMed 34437304
  • Reynolds EL, Akinci G, Banerjee M, Looker HC, Patterson A, Nelson RG, Feldman EL, Callaghan BC. The determinants of complication trajectories in American Indians with type 2 diabetes. JCI Insight. 2021 May 24;6(10):e146849. doi: 10.1172/jci.insight.146849.

    PubMed 34027894
  • Afshinnia F, Nair V, Lin J, Rajendiran TM, Soni T, Byun J, Sharma K, Fort PE, Gardner TW, Looker HC, Nelson RG, Brosius FC, Feldman EL, Michailidis G, Kretzler M, Pennathur S. Increased lipogenesis and impaired beta-oxidation predict type 2 diabetic kidney disease progression in American Indians. JCI Insight. 2019 Nov 1;4(21):e130317. doi: 10.1172/jci.insight.130317.

    PubMed 31573977
  • Tanamas SK, Saulnier PJ, Fufaa GD, Wheelock KM, Weil EJ, Hanson RL, Knowler WC, Bennett PH, Nelson RG. Long-term Effect of Losartan on Kidney Disease in American Indians With Type 2 Diabetes: A Follow-up Analysis of a Randomized Clinical Trial. Diabetes Care. 2016 Nov;39(11):2004-2010. doi: 10.2337/dc16-0795. Epub 2016 Sep 9.

    PubMed 27612501
  • Weil EJ, Lemley KV, Mason CC, Yee B, Jones LI, Blouch K, Lovato T, Richardson M, Myers BD, Nelson RG. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy. Kidney Int. 2012 Nov;82(9):1010-7. doi: 10.1038/ki.2012.234. Epub 2012 Jun 20.

    PubMed 22718189

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Losartan in people with Diabetic Nephropathy, 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 8 inclusion and 13 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 25 Mar 2021. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Decline in GFR (time frame: Up to 6 years). 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 NCT00340678, which also lists 10 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 25 Mar 2021.

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