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

Primary Purpose

Diabetic Nephropathy Type 2

Status

Withdrawn

Phase

Phase 4

Locations

Denmark

Study Type

Interventional

Intervention

Linagliptin

Empagliflozin

Telmisartan

Sulodexide

About this trial

This is an interventional treatment trial for Diabetic Nephropathy Type 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Steno Diabetes Center Copenhagen

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Intervention

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Correlation of albuminuria-lowering response.

The first secondary outcome is the degree of correlation in albuminuria-lowering responses between drugs within individual patients during the four treatment periods.

Effect on glycocalyx.

The second secondary outcome is the effect of the four drugs on the glycocalyx.

Full Information

NCT ID

NCT03504566

First Posted

April 12, 2018

Last Updated

September 12, 2018

Sponsor

Steno Diabetes Center Copenhagen

Collaborators

University Medical Center Groningen

1. Study Identification

Unique Protocol Identification Number

NCT03504566

Brief Title

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

Acronym

ROTATE-2

Official Title

Rotation for Optimal Targeting of Albuminuria and Treatment Evaluation: A Rotation Study of Different Albuminuria Lowering Drug Classes to Study Individual Drug Response in Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Withdrawn

Why Stopped

Registered and published incorrectly

Study Start Date

November 15, 2017 (Actual)

Primary Completion Date

June 1, 2019 (Anticipated)

Study Completion Date

June 1, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Steno Diabetes Center Copenhagen

Collaborators

University Medical Center Groningen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Standard treatment to patients with diabetes and persistent albuminuria nowadays are drugs inhibiting the RAAS-system as these thus assert renoprotective effects. It has been shown, that many patients do not respond to these, which means that many remain at a high renal and cardiovascular risk and highlights the need to understand the drug response variability and to find alternative albuminuria lowering treatments in order to optimize treatment for each individual. Various drugs other than RAAS-inhibitors are available, that also decreases albuminuria. However, whether individual patients not responding to these beneficially respond to other albuminuria lowering drugs has not been prospectively investigated. Therefore a better understanding on the individual response to different albuminuria lowering drugs, of which some are developed for another indication, may help to tailor optimal therapy. This study is designed as a randomized multicenter crossover trial with a total duration of 48 weeks and with a total of 52 patients diagnosed with type 2 diabetes, as well as elevated albuminuria (UACR between 50 mg/g and 500 mg/g).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Nephropathy Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Other

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Linagliptin

Intervention Description

Linagliptin

Intervention Type

Drug

Intervention Name(s)

Empagliflozin

Intervention Description

Empagliflozin

Intervention Type

Drug

Intervention Name(s)

Telmisartan

Intervention Description

Telmisartan

Intervention Type

Drug

Intervention Name(s)

Sulodexide

Intervention Description

Sulodexide

Primary Outcome Measure Information:

Title

Strongest albuminuria-lowering effect.

Description

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.

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

Correlation of albuminuria-lowering response.

Description

The first secondary outcome is the degree of correlation in albuminuria-lowering responses between drugs within individual patients during the four treatment periods.

Time Frame

48 weeks

Title

Effect on glycocalyx.

Description

The second secondary outcome is the effect of the four drugs on the glycocalyx.

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Facility Information:

Facility Name

Steno Diabetes Center Copenhagen

City

Gentofte

ZIP/Postal Code

2820

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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