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Type 1 DiabetesPhase 2NCT00143949

Renin Angiotensin System Study (RASS/B-RASS)

A Phase 2 study testing enalapril and losartan in people with Type 1 Diabetes, run by Michael Mauer, MD at 3 sites in Canada.

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

To determine if renin angiotensin medications can prevent or delay the onset of diabetic kidney disease. Read more about this study

Who is it for?
Ages 16 to 61 yearsHealthy volunteers can take part
Conditions the study is for
Type 1 Diabetes
What is being tested?
enalapril and losartan
How many people
285 participants
Where
3 sitesCanada
Study dates
Mar 1997to May 2008
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 16 to 61 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • type 1 diabetic (DM) for 2-20 yrs
  • type 1 DM onset prior to 45; if onset was between ages 31-41, BMI <26; onset 41-45, positive GAD or ICA required
  • normal or increased GFR
  • normal BP
  • normoalbuminuric (<20 ug/min on 2 of 3 time overnight urine collections)

Who cannot join

  • type 1 DM duration longer than 20 yrs
  • hypertension (>85/135 mmHg)
  • reduced GFR (<90 ml/min/1.73m2)
  • microalbuminuria
  • solitary kidney or evidence of unilateral renal disease
  • evidence of other important kidney disease by history, ultrasound or biopsy
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  • other chronic diseases or conditions such as cystic fibrosis, serious mental illness, severe mental retardation, etc.
  • pregnancy or females planning pregnancy within 2 years were excluded due to the drugs being used
  • compliance (pt not taking at least 85% of two week placebo were excluded)

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Royal Victoria Hospital, McGill University (Data Center)

    Montreal, Quebec, H3A 1A1

  • Montreal Childrens Hospital, McGill University (Clinical Ctr)

    Montreal, Quebec, H3H 1P3

  • Mt Sinai Hospital, University of Toronto (Clinical Ctr)

    Toronto, Ontario, M5G 1X5

Other trials in Canada

About this study

Official title: Renin Angiotensin System Blockage-DN (RASS)

To determine if renin angiotensin medications can prevent or delay the onset of diabetic kidney disease.

Read the detailed description

The primary objective of this research is to determine, in type 1 (insulin-dependent) diabetic patients without hypertension, diabetic nephropathy (DN), or levels of microalbuminuria (MA) predictive of underlying, already established serious lesion of diabetic nephropathy, if inhibition of renin-angiotensin system (RAS) activity can prevent or retard the rate of development of the histologic lesions associated with DN. This primary prevention study is designed to examine the effect of pharmacologic intervention on the earliest stages of diabetic kidney disease. At the stage of overt DN intervention studies have shown only a slowing, as opposed to arrest, in disease progression, and benefit a minority of treated patients. At the MA stage the renal lesions of DN are already usually firmly established; moreover, progression in MA patients may occur despite strict glycemic or anti-hypertensive control. Renal histologic change over time has been selected as the primary endpoint in order to study the early stages of this disease, since the time to functional endpoints from these earlier stages precludes practical study design.

Specific Aim 1 To recruit 285 type 1 diabetic patients who do not have hypertension, diabetic nephropathy, or predictive levels of microalbuminuria into a 5-year study to determine the effect of inhibition of renin-angiotensin system activity with either losartan (angiotensin II blocker) or enalapril (converting enzyme inhibitor) on the development of diabetic renal disease. This aim has been accomplished and the study is entitled the Renin-Angiotension System Study (RASS).

Specific Aim 2 To obtain two percutaneous renal biopsies from each patient, the first, at entry into the study, and the second after five years of drug therapy with either losartan or enalapril.

Hypothesis Reduction of renin-angiotensin system activity will prevent or retard the development of histologic change in the kidney associated with diabetic nephropathy.

A secondary objective of this study is to evaluate retinal lesions in the RASS cohort of patients in order to determine the relationship of these findings to the histologic changes of DN and to examine the effects of RAS inhibition and/or systemic blood pressure (BP) on the development and progression of diabetic retinopathy. This ancillary study has the following aims:

Specific Aim To obtain baseline, 2.5 and 5 year retinal fundus photographs in the RASS patients.

Hypothesis Cross-sectional and longitudinal relationships of retinal and renal structural abnormalities will emerge which will improve the predictive value of renal functional tests. Reduction of rennin-angiotensin system activity will prevent or retard the development of diabetic retinal lesions

Conditions
Type 1 Diabetes
Being tested
enalapril, losartan
Keywords
diabetes, nephropathy, kidney, retinopathy
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus, Kidney Diseases, Retinal Diseases

What participants receive

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

  • enalaprilDrug

  • losartanDrug

What is being measured

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

  1. To recruit 285 type 1 DM Pts without HTN, diabetic nephropathy, or microalbuminuria into a 5-year study to determine the effect of inhibition RAS with either losartan or enalapril.

    Measured: 5 year

  2. To obtain two percutaneous renal biopsies from each patient, five years apart.

    Measured: 5 year

Secondary outcomes (1)

  1. To evaluate retinal lesions in RASS cohort to determine relationship to the histologic changes of DN and the effects of RAS inhibition and/or systemic blood pressure.

    Measured: 5 year

Timeline

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

  1. First posted2 Sep 2005 (estimated)
  2. Study startMar 1997
  3. Primary completionMar 2007
  4. Study completionMay 2008

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
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
285 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00143949
Sponsor's protocol ID
9601M10705
Status last verified
Nov 2008
First submitted
1 Sep 2005
Last updated
6 Nov 2008
Results posted
No
Data monitoring committee
Yes

Publications

  • Mauer M, Zinman B, Gardiner R, Drummond KN, Suissa S, Donnelly SM, Strand TD, Kramer MS, Klein R, Sinaiko AR. ACE-I and ARBs in early diabetic nephropathy. J Renin Angiotensin Aldosterone Syst. 2002 Dec;3(4):262-9. doi: 10.3317/jraas.2002.048.

    PubMed 12584670

  • Limonte CP, Prince DK, Hoofnagle AN, Galecki A, Hirsch IB, Tian F, Waikar SS, Looker HC, Nelson RG, Doria A, Mauer M, Kestenbaum BR, de Boer IH. Associations of Biomarkers of Tubular Injury and Inflammation with Biopsy Features in Type 1 Diabetes. Clin J Am Soc Nephrol. 2024 Jan 1;19(1):44-55. doi: 10.2215/CJN.0000000000000333. Epub 2023 Oct 23.

    PubMed 37871959

  • Robiner WN, Strand TD, Mauer M; Renin Angiotensin System Study (RASS) Group. Adherence and renal biopsy feasibility in the Renin Angiotensin-System Study (RASS) primary prevention diabetes trial. Diabetes Res Clin Pract. 2013 Oct;102(1):25-34. doi: 10.1016/j.diabres.2013.06.004. Epub 2013 Sep 17.

    PubMed 24050942

  • Harindhanavudhi T, Mauer M, Klein R, Zinman B, Sinaiko A, Caramori ML; Renin Angiotensin System Study (RASS) group. Benefits of Renin-Angiotensin blockade on retinopathy in type 1 diabetes vary with glycemic control. Diabetes Care. 2011 Aug;34(8):1838-42. doi: 10.2337/dc11-0476. Epub 2011 Jun 29.

    PubMed 21715517

  • Klein R, Myers CE, Klein BE, Zinman B, Gardiner R, Suissa S, Sinaiko AR, Donnelly SM, Goodyer P, Strand T, Mauer M. Relationship of blood pressure to retinal vessel diameter in type 1 diabetes mellitus. Arch Ophthalmol. 2010 Feb;128(2):198-205. doi: 10.1001/archophthalmol.2009.391.

    PubMed 20142543

  • Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, Drummond K, Donnelly S, Goodyer P, Gubler MC, Klein R. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009 Jul 2;361(1):40-51. doi: 10.1056/NEJMoa0808400.

    PubMed 19571282

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing enalapril and losartan in people with Type 1 Diabetes, run by Michael Mauer, MD at 3 sites in Canada.

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 5 inclusion and 9 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 6 Nov 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. 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?

To recruit 285 type 1 DM Pts without HTN, diabetic nephropathy, or microalbuminuria into a 5-year study to determine the effect of inhibition RAS with either losartan or enalapril. (time frame: 5 year). The study lists 2 primary outcomes in all. 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 NCT00143949, which also lists 6 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 6 Nov 2008.

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