Diabetic Nephropathy Type 2Phase 4ROTATE-2NCT03504566
Rotation for Optimal Targeting of Albuminuria and Treatment Evaluation (ROTATE-2)
A Phase 4 study testing Linagliptin, Empagliflozin and Telmisartan in people with Diabetic Nephropathy Type 2, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Nephropathy Type 2
- What is being tested?
- Linagliptin, Empagliflozin and Telmisartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteDenmark
- Study dates
- 15 Nov 2017to 1 Jun 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes
- eGFR > 45ml/min/1.73m2
- Albumin:creatinine ratio >50mg/g and ≤500 mg/g
- Age ≥ 18 years
- Written informed consent
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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).
- Conditions
- Diabetic Nephropathy Type 2
- Being tested
- Linagliptin, Empagliflozin, Telmisartan, Sulodexide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinagliptinDrug
Linagliptin
EmpagliflozinDrug
Empagliflozin
TelmisartanDrug
Telmisartan
SulodexideDrug
Sulodexide
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Linagliptin; Drug: Empagliflozin; Drug: Telmisartan; Drug: Sulodexide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 weeks
Secondary outcomes (2)
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.
Measured: 48 weeks
Effect on glycocalyx.
The second secondary outcome is the effect of the four drugs on the glycocalyx.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2018
- Study start15 Nov 2017
- Primary completion1 Jun 2019 (estimated)
- Study completion1 Jun 2019 (estimated)
Why it stopped: Registered and published incorrectly
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Nephropathy Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen
- Responsible party
- Principal investigator, Peter Rossing, Steno Diabetes Center Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03504566
- Sponsor's protocol ID
- H-17013487
- Acronym
- ROTATE-2
- Status last verified
- Sep 2018
- First submitted
- 12 Apr 2018
- Last updated
- 14 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03504566
- Acronym / sponsor ID
- ROTATE-2 / H-17013487
- Conditions
- Diabetic Nephropathy Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Registered and published incorrectly
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- University Medical Center Groningen
- Study start
- 15 Nov 2017 (actual)
- Primary completion
- 1 Jun 2019 (estimated)
- Study completion
- 1 Jun 2019 (estimated)
- First posted
- 20 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Other | Drug: Linagliptin, Drug: Empagliflozin, Drug: Telmisartan, Drug: SulodexideAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Type 2 diabetes
- eGFR > 45ml/min/1.73m2
- Albumin:creatinine ratio >50mg/g and ≤500 mg/g
- Age ≥ 18 years
- Written informed consent
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LinagliptinLinagliptin | Drug | Intervention |
| EmpagliflozinEmpagliflozin | Drug | Intervention |
| TelmisartanTelmisartan | Drug | Intervention |
| SulodexideSulodexide | Drug | Intervention |
Primary outcome
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.
2 secondary outcomes
Correlation of albuminuria-lowering response.
Time frame: 48 weeks
Effect on glycocalyx.
Time frame: 48 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Linagliptin, Empagliflozin and Telmisartan in people with Diabetic Nephropathy Type 2, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Strongest albuminuria-lowering effect. (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2018.