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

NCT03504566 | Withdrawn Phase 4 DMC

• 1 other identifier: H-17013487
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetic Nephropathy Type 2

Outcome Measures

Primary Outcomes (1)

• Strongest albuminuria-lowering effect.

  Proportion of patients in whom the drug selected in the fifth treatment period exerts the strongest albuminuria lowering effect as compared to the other drugs used during the treatment periods.

  48 weeks

Secondary Outcomes (2)

• Correlation of albuminuria-lowering response.

  48 weeks

• Effect on glycocalyx.

  48 weeks

Study Arms (1)

Intervention

OTHER

All patients recieve, in randomomized order a four way treatment schedule. Due to the nature of the study, the individual patient will serve as his/hers own comparator.

Drug: Linagliptin; Drug: Empagliflozin; Drug: Telmisartan; Drug: Sulodexide

Interventions

Linagliptin DRUG

Linagliptin

Intervention

Empagliflozin DRUG

Empagliflozin

Intervention

Telmisartan DRUG

Telmisartan

Intervention

Sulodexide DRUG

Sulodexide

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes
• eGFR \> 45ml/min/1.73m2
• Albumin:creatinine ratio \>50mg/g and ≤500 mg/g
• Age ≥ 18 years
• Written informed consent

You may not qualify if:

• 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).
• 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 urinary obstruction of difficulty in voiding at screening

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• University Medical Center Groningen: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

MeSH Terms

Interventions

Linagliptin; empagliflozin; Telmisartan; glucuronyl glucosamine glycan sulfate

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 12, 2018
• First Posted: April 20, 2018
• Study Start: November 15, 2017
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: September 14, 2018

Record last verified: 2018-09

Locations

DK (1)