The main objective of the study is to determine the albuminuria lowering effect of the GLP1-RA exenetide, SGLT-2 inhibitor dapagliflozin and their combination in patients with type 2 diabetes and micro- or macroalbuminuria.Secondary objectives are…
ID
Source
Brief title
Condition
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is the change in albuminuria from baseline at the end
of each treatment period.
Secondary outcome
* To assess the correlation in albuminuria-lowering response of dapagliflozin
and exenatide within each individual
* To assess the effect of dapagliflozin, exenatide and their combination on
extracellular volume
* To evaluate the correlation between change in extracellular volume and effect
on albuminuria
* To assess the effect of dapagliflozin, exenatide and their combination on
fractional lithium excretion
* To assess the effect of dapagliflozin, exenatide and their combination on
blood pressure
* To assess the effect of dapagliflozin, exenatide and their combination on
weight
* To evaluate the correlation between the pharmacokinetics of dapagliflozin and
exenatide and their albuminuria lowering effect
* To assess the effect of dapagliflozin, exenatide and their combination renal
parameters as measured with MRI
* To assess the effect of dapagliflozin, exenatide and their combination on
liver fat as measured with MRI
Background summary
Glucagon-like peptide receptor agonists (GLP1-RA) and sodium-glucose
co-transporter 2 (SGLT-2) inhibitors are the two latest new drug classes for
the management of type 2 diabetes. These drugs lower HbA1c when given as
monotherapy or as adjunct to other glucose lowering drugs. Interestingly, both
drug classes show beneficial effects on multiple cardiovascular risk factors
such as body weight, blood pressure and albuminuria and they have been shown to
reduce renal and cardiovascular risk. It is unknown whether the combination of
both drug classes confers an even more beneficial effect than either treatment
alone.
Study objective
The main objective of the study is to determine the albuminuria lowering effect
of the GLP1-RA exenetide, SGLT-2 inhibitor dapagliflozin and their combination
in patients with type 2 diabetes and micro- or macroalbuminuria.
Secondary objectives are to assess the correlation in albuminuria-lowering
response of dapagliflozin and exenatide within each individual, to assess the
effect of dapagliflozin, exenatide and their combination on extracellular
volume, to evaluate the correlation between change in extracellular volume and
effect on albuminuria, to assess the effect of dapagliflozin, exenatide and
their combination on blood pressure and weight, to evaluate the correlation
between the pharmacokinetics of dapagliflozin and exenatide and their
albuminuria lowering effect, and to assess changes in renal parameters and
liver fat as measured with MRI during treatment with dapagliflozin, exenatide
and their combination.
Study design
A randomized, prospective, single centre, crossover trial with a total duration
of 45 weeks per patient.
Intervention
Patients receive in random order 6 weeks of treatment with the GLP1-RA
exenatide 2 mg/week s.c., 6 weeks of treatment with the SGLT-2 inhibitor
dapagliflozin 10 mg/day and 6 weeks of treatment with the combination of
exenatide and dapagliflozin, with 9-weeks wash-out periods in between.
Study burden and risks
At the beginning and end of each treatment period blood is collected for
clinical chemistry. Patients are requested to collect three consecutive first
morning void urine samples at the beginning and end of each treatment period,
and one additional first morning void urine sample halfway the treatment
period. Extracellular volume and total body water will be measured at the
beginning and end of each treatment period with a bio-impedance spectrometer.
MRI scans of the kidney and the liver are performed at the start and at the end
of each treatment periode. There are no direct benefits for the patients to be
included and participation is on a free-will base.
Van Swietenplein 1
Groningen 9728 NT
NL
Van Swietenplein 1
Groningen 9728 NT
NL
Listed location countries
Age
Inclusion criteria
* Type 2 diabetes
* HbA1c * 6.5% (48 mmol/mol)
* eGFR > 30 ml/min/1.73m2
* Albumin:creatinine ratio >3.5mg/mmol and *100 mg/mmol
* Age * 18 years
* Written informed consent
Exclusion criteria
* Pregnant women and women of child-bearing potential who are not using reliable contraception
* Cardiovascular disease: myocardial infarction, angina pectoris, percutanous transluminal coronary angioplasty, coronary artery bypass grafting, stroke, heart failure (NYHA I-IV) < 6 months before inclusion
* Uncontrolled blood pressure (> 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.
* 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.
* Use of SGLT-2 inhibitor, GLP1-RA or DPP-4 inhibitor.
* Lithium use
* Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications
* Any condition when MRI is contraindicated
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-004709-42-NL |
| CCMO | NL63792.099.18 |
| OMON | NL-OMON24855 |