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

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ClinicalTrials.gov Identifier: NCT03504566
Recruitment Status : Withdrawn (Registered and published incorrectly)
First Posted : April 20, 2018
Last Update Posted : September 14, 2018
Sponsor:
Collaborator:
University Medical Center Groningen
Information provided by (Responsible Party):
Peter Rossing, Steno Diabetes Center Copenhagen

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.

Condition or disease Intervention/treatment Phase
Diabetic Nephropathy Type 2 Drug: Linagliptin Drug: Empagliflozin Drug: Telmisartan Drug: Sulodexide Phase 4

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 15, 2017
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : June 1, 2019

Arm Intervention/treatment
Intervention
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
Linagliptin

Drug: Empagliflozin
Empagliflozin

Drug: Telmisartan
Telmisartan

Drug: Sulodexide
Sulodexide




Primary Outcome Measures :
  1. Strongest albuminuria-lowering effect. [ Time Frame: 48 weeks ]
    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 :
  1. Correlation of albuminuria-lowering response. [ Time Frame: 48 weeks ]
    The first secondary outcome is the degree of correlation in albuminuria-lowering responses between drugs within individual patients during the four treatment periods.

  2. Effect on glycocalyx. [ Time Frame: 48 weeks ]
    The second secondary outcome is the effect of the four drugs on the glycocalyx.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03504566


Locations
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Denmark
Steno Diabetes Center Copenhagen
Gentofte, Denmark, 2820
Sponsors and Collaborators
Steno Diabetes Center Copenhagen
University Medical Center Groningen

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Responsible Party: Peter Rossing, Professor, Steno Diabetes Center Copenhagen
ClinicalTrials.gov Identifier: NCT03504566     History of Changes
Other Study ID Numbers: H-17013487
First Posted: April 20, 2018    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Diabetic Nephropathies
Albuminuria
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Proteinuria
Urination Disorders
Urological Manifestations
Signs and Symptoms
Empagliflozin
Linagliptin
Glucuronyl glucosamine glycan sulfate
Telmisartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Sodium-Glucose Transporter 2 Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anticoagulants
Hypolipidemic Agents