Type 1 diabetes with albuminuria MedDRA version: 20.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Micardis
Pharmaceutical Form:
INN or Proposed INN: TELMISARTAN
CAS Number: 144701-48-4
Trade Name: Jardiance
Pharmaceutical Form:
CAS Number: 864070-44-0
Other descriptive name: EMPAGLI
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Type 1 diabetes • eGFR > 45ml/min/1.73m2 • Albumin:creatinine ratio >50mg/g and =500 mg/g • Age = 18 years • Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 26 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Pregnant women and women of child-bearing potential who are not using reliable contraception • Cardiovascular disease: myocardial infarction, angina pectoris, percutanous transluminal coronary angioplasty, coronary artery bypass grafting, stroke, heart failure (NYHA I-IV) 160/ 100 mmHg) • Active malignancy • History of autonomic dysfunction (e.g. history of fainting or clinically significant orthostatic hypotension) • Participation in any clinical investigation within 3 months prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. • Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing • History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening. • Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: o Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; o Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months; o Pancreatic injury or pancreatitis within the last six months; o Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at inclusion visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt; o Evidence of urinary obstruction of difficulty in voiding at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: A better understanding on the individual response to different albuminuria lowering drugs and a better understanding why these drugs, of which some are developed for another indication, may help to tailor optimal therapy. Therefore in this study individual patients will be subjected to four different drug classes that have all been shown to reduce albuminuria on a group level. The drug that induces the strongest albuminuria-lowering response will be repeated in a fifth treatment period to assess whether the albuminuria lowering effect can be confirmed in a second treatment period to ascertain the consistency of the individual response.;Secondary Objective: The secondary objective of this study is to investigate the effect of different albuminuria lowering interventions on the glycocalyx. It has been shown that the glycocalyx plays an important role in the pathogenesis of diabetic kidney disease. The glycocalyx is a gel-like structure which is composed of protein-cores connected to heparan sulfate and chondroitin sulfate side-chains. The glycocalyx covers the endothelium and because of its negative charge forms an important barrier against albumin filtration. It has been shown that the glycocalyx dimension is significantly smaller in patients with type 2 diabetes compared to healthy controls. Treatment with albuminuria-lowering drugs may assert their beneficial effect through restoring perturbations in the glycocalyx. We therefore aim to measure the thickness of the glycocalyx during treatment with each of the four drug classes and correlate this to the albuminuria-lowering response.;Primary end point(s): Albuminuria reduction;Timepoint(s) of evaluation of this end point: After 4 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Glycocalyx thickness;Timepoint(s) of evaluation of this end point: After 4 weeks of treatment | — |
Countries
Denmark, Netherlands
Outcome results
None listed