Patients with type 2 diabetes mellitus and normoalbuminuria MedDRA version: 18.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Steno Diabetes Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent must be provided before participation. Patient information and consent form must be approved by relevant independent EC. Specifically, all participating patients will be asked to give informed consent for long-term follow-up and collection of follow-up data • Male or female patients = 18 years and 45 ml/min/1.73m2 at Screening visit • The patient must be willing and able to comply with the protocol for the duration of the study • Female without child-bearing potential at the screening visit. Defined as one or more of following: - Female patients = 50 years of age at the day of inclusion, who have been postmenopausal for at least 1 year - Female patients 40 mIU/mL as well as serum estrogen levels =65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: • Average of systolic BP 160 mm Hg at baseline • Average of diastolic BP > 100 mm Hg at baseline • Type 1 DM (WHO criteria) • HbA1c 5 years of known duration of diabetes type 2 AND never treated with a antidiabetic drug of any kind. • Current in treatment with more than one RAAS blocking agent (Angiotensin Converting Enzyme inhibitor, Angiotensin Receptor Blocker or Direct Renin Inhibitor) • Current lithium treatment (ATC: N05AN) • Known or suspected hypersensitivity to Spironolactone or to any of its excipients • Current use of potassium sparing diuretics (ATC: C03D, C03E), such as: Spironolactone, Eplerenone or amiloride etc • Hyperkalemia at Screening: plasma potassium level >5.0 mmol/L or serum potassium level >5.4 mmol/L. • Hyponatriemia determine by the investigator • Current cancer treatment or within five years from baseline (except basal cell skin cancer or squamous cell skin cancer) • Any clinically significant disorder, except for conditions as-sociated with type 2 DM history, which in the Investigators opinion could interfere with the results of the trial • Cardiac disease defined as: Heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or MI, stroke, PTCA or CABG within the last 3 months • Diagnosis of non-Diabetic CKD current or in the past • Diagnosis of liver cirrhosis with current impaired liver function within the last 3 years. • Diagnosis of Addison's disease • Being lactating • Intend to become pregnant within the duration of the study or not use adequate birth control. • Known or suspected abuse of alcohol or narcotics • Not able to understand informed consent form • Participation in any other intervention trial than PRIORITY or a related sub-study is not allowed within 30 days before inclusion or concurrent to this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To confirm that urinary proteomics can predict development of microalbuminuria (as a surrogate marker for the development of overt nephropathy) in a cohort of 2000 type 2 diabetic patients with normal urinary albumin excretion.;Primary end point(s): Development of confirmed microalbuminuria (UACR>30 mg/g) in at least two out of three first morning voids with = 30% increase (ge-ometric mean) in UACR from “run-in” period samples OR > 40mg/g (geometric mean).; Secondary Objective: -To investigate if early initiation of preventive therapy with spironolactone 25 mg once daily reduces risk of transition to microalbuminuria in those patients identified by urinary proteomics to be at high risk -Assessment of safety in the intervention group -To compare the rate of change in UAER in high- vs. low-risk patients (based on the proteomic test), and to compare the effect of spironolactone on rate of change in UACR in the intervention study. -In addition, the objective is to study the rate of change in eGFR in relation to urinary marker pattern (CKD 273) and the intervention with spironolactone. -To study the ability of urinary proteomic patterns to predict cardiovascular or renal events during the study, as well as response to intervention in relation to study endpoints -To establish a biobank that will allow testing of additional putative markers for progression of diabetic nephropathy, development of cardiovascular events and death ; Timepoint(s) of evaluation of this end point: Every 13 weeks and at planned end (July to September 2018) or early termination (treatment group) Every 52 weeks and at planned end (July to September 2018) or early termination (observational group) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1), 3), 8) during the study 2), 9) Data collected from self-reported AEs 4), 5), 10), 11) run-in period, every 13 weeks, at planned end (July to September 2018) or early termination (treatm. group), run-in period, every 52 weeks, at planned end (Jul to Sep 2018) or early termination (obs. group) 6),12) screening/baseline, Visit 1, every 13 weeks, at planned end or early termination (treatm. group); every 52 weeks and at planned end or early termination (obs. group) 7), 13) baseline, every 13 weeks and at planned end or early termination (treatm. group); every 52 weeks and at planned end or early termination (obs. group) 14) baseline, every Visit, prolonged until all AEs are resolved or until the investigator assess the adverse events as "chronic" or "stable". ; Secondary end point(s): In the following paragraphs patients in the intervention group, (group B) and observation group (group A) will be compared 1) Comparison of composite fatal and non-fatal cardiovascular outcome (MI, stroke, CABG, PTCA, hospitalization for heart failure and CVD), and all cause mortality during the study 2) Comparison of incidence of retinopathy and frequency of laser treatment. Data collected from self-reported AEs 3) In addition to the categorical analysis of urinary albumin excretion, an analysis will be performed with changes in geometric mean albuminuria throughout the study period in all patients by assessing the slope of albuminuria changes and absolute changes from inclusion to end of trial 4) Development of microal | — |
Countries
Belgium, Czech Republic, Denmark, Germany, Greece, Italy, Macedonia, the former Yugoslav Republic of, Netherlands, Spain, United Kingdom
Contacts
Public ContactProf. Peter Rossing MD. DMSc
Steno Diabetes Center
Outcome results
None listed