Rotation for Optimal Targeting of Albuminuria and Treatment Evaluation (ROTATE-2)

• Status: Withdrawn
• Trial end date: 2019-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This project is an intervention study where type 2 diabetic patients will rotate through 4 different albuminuria lowering drugs with the aim to 1) quantify the individual relationship between drug exposure and albumin lowering response of different albuminuria lowering drugs in type 1 and type 2 diabetics; and 2) to investigate the effect of the same drug intervention on the glycocalyx layer in blood vessels. The overall purpose of this study is to allow for future personalized treatment of diabetics with regards to treating kidney disease more effectively than current standardized strategies.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Steno Diabetes Center; Steno Diabetes Center Copenhagen
• Collaborator: University Medical Center Groningen
• Treatments: Empagliflozin; Glucuronyl glucosamine glycan sulfate; Linagliptin; Telmisartan

Criteria

Inclusion Criteria:

• Type 2 diabetes

• eGFR > 45ml/min/1.73m2

• Albumin:creatinine ratio >50mg/g and ≤500 mg/g

• Age ≥ 18 years

• Written informed consent

Exclusion Criteria:

• Pregnant women and women of child-bearing potential who are not using reliable contraception . In addition, fertile women included in the trial must use contraceptive methods in line with the below throughout the entire trial period and until the end of relevant systemic exposure for human teratogenicity/fetal toxicity. Approved contraceptives are intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release).

• Cardiovascular disease: myocardial infarction, angina pectoris, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, stroke, heart failure (NYHA I-IV) < 6 months before inclusion

• Uncontrolled blood pressure (office BP > 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.

• Hypersensitivity to study drugs and their excipients

• 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:

• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;

• Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;

• Pancreatic injury or pancreatitis within the last six months;

• 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;

• Evidence of urinary obstruction of difficulty in voiding at screening