To explore the inflammatory changes of dapagliflozin compared with placebo on postprandial lipemia and postprandial leukocyte activation, oxidative stress and endothelial function in men with type 2 diabetes mellitus using insulin.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Lipid metabolism disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study endpoint will be postprandial leukocyte activation, measured by
CD35, CD11b and CD66b.
Secondary outcome
Secondary endpoints will be postprandial lipemia (plasma apoB, HDL-c, LDL-c,
total cholesterol and triglycerides), oxidative stress (lipoperoxidase) and
vascular function (arterial pulse wave velocity and arterial pulse wave
analysis). Furthermore, we will measure fasting and postprandial levels of free
fatty acids and b-hydroxybutyrate, to explore the molecular mechanisms involved
in SGLT2 inhibition related to lipid metabolism.
Background summary
Few studies have proven to be efficient in reducing cardiovascular risk in
diabetes. Recently, a SGLT2-inhibitor showed a significant reduction in
cardiovascular mortality without a clear mechanism for this reduction.
Treatment with dapagliflozin will reduce postprandial hyperlipidemia and thus
reduce postprandial leukocyte activation, diminish the generation of
postprandial oxidative stress and improve postprandial vascular dysfunction in
men with type 2 diabetes mellitus.
Study objective
To explore the inflammatory changes of dapagliflozin compared with placebo on
postprandial lipemia and postprandial leukocyte activation, oxidative stress
and endothelial function in men with type 2 diabetes mellitus using insulin.
Study design
Randomized, double blind pilot study.
Intervention
Two oral fat load tests (OFLTs) will be performed. After the first OFLT,
volunteers will be randomly assigned to receive 12 weeks of either
dapagliflozin daily or a placebo. Twelve weeks later the OFLT will be repeated.
Study burden and risks
The use of a SGLT-2 inhibitor daily has been established to be a safe and
effective treatment for type 2 diabetes mellitus. Volunteers will be
hospitalized on 2 different days (day 1, day 85) for approximately nine hours
each day and receive an oral fat load. Glucose will be monitored and controlled
according to an individual algorithm. The volunteers* general practitioner will
be informed on their participation. A total of 222ml (111ml for each
postprandial test) of blood will be drawn. Volunteers will be allowed to drink
only water during the tests. There is a theoretical risk of hypoglycemia but no
excessive risk is involved. Volunteers receive 250 euros for full
participation. Furthermore, volunteers will be informed and given advice if
they turn out to have an increased cardiovascular risk or any other condition.
Kleiweg 500
Rotterdam 3045 PM
NL
Kleiweg 500
Rotterdam 3045 PM
NL
Listed location countries
Age
Inclusion criteria
- Age of 18 years of older
- Male sex
- Diabetes mellitus type II on intensive insulin treatment (three times short acting and once daily long acting)(unchanged for >10 weeks prior to inclusion
- Stable glucose regulation last 6 months (HbA1c >6.5% - <9%)
- Provision of informed consent prior to any study procedure
Exclusion criteria
- Current smoking
- Impaired renal function (MDRD <60 ml/min/1.73m2)
- Recent use of SGLT2 inhibitior (past 6 months)
- Recent cardiovascular event (past 6 months) (myocardial infarction, coronary artery bypass grafting, stroke)
- Severe hyperglycemic events in the past 6 months (hyperglycemie > 20mmol/l requiring hospital admission)
- Provision of informed consent prior to any study procedure
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous enrollment in the present study
- Participation in another clinical study with an investigational product during the last 6 months
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 | EUCTR2016-001417-24-NL |
| CCMO | NL57393.101.16 |
| OMON | NL-OMON21590 |