Primary Objective: To determine whether a four week treatment with vildagliptin compared to acarbose improves endothelial dysfunction in patients with type 2 diabetes mellitus.Secondary Objective(s):-To determine the effect of vildagliptin on plasma…
ID
Source
Brief title
Condition
- Diabetic complications
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Forearm vasodilatory response to increasing doses of intra-arterially
administered acetylcholine and sodium nitroprusside (three doses each)
following 4 week treatment with vildagliptin and acarbose.
Secondary outcome
Signs of vascular inflammation following treatment with both vildagliptin and
acarbose, assessed by
• Cytokines (Il-6, hsCRP, Il-18)
• Adipokines
Local effects on fat tissue following treatment with both vildagliptin and
acarbose, assessed by
• Fat cell size and morphology
• Gene expression of GLUT4, adiponectin, PPARγ, Il-1β and Il-18
Changes in ex vivo mononuclear cell responses to various stimuli following
treatment with both vildagliptin and acarbose
Background summary
Cardiovascular complications in type 2 diabetes are the leading cause of
morbidity and mortality associated with the disease. Endothelial dysfunction is
an important pathogenetic factor in these vascular complications.
Recently, new blood glucose lowering agents have been introduced for the
treatment of type 2 diabetes. These new agents influence the incretin system.
Glucagon like peptide-1, GLP-1, one of the incretin hormones, stimulates the
release of insulin. GLP-1 is produces by the L cells throughout the
gastrointestinal tract and is rapidly degraded in the circulation to GLP-1
(9-36) by dipeptidyl peptidase IV (DPP-IV). This rapid degradation causes a
very short halflife time of GLP-1 in the circulation. This has led to the
introduction of longacting GLP-1 agonists and DPP-IV inhibitors as treatment
for type 2 diabetes.
GLP-1 ameliorates endothelial function in mammals and humans.
We want to investigate the effect of DPP-IV inhibition on endothelial function
in humans with type 2 diabetes.
Study objective
Primary Objective: To determine whether a four week treatment with vildagliptin
compared to acarbose improves endothelial dysfunction in patients with type 2
diabetes mellitus.
Secondary Objective(s):
-To determine the effect of vildagliptin on plasma levels of inflammatory
markers and adipokines following a four week treatment
-To determine the effect of vildagliptin on fat cell morphology and gene
expression following a four week treatment
- To determine the effect of vildagliptin on peripheral blood mononuclear cell
responses to various stimuli following a four week treatment with vildagliptin
compared to acarbose
Study design
This is a randomised, double blind, single centre, intervention study with a
cross-over design.
Intervention
Four week treatment with vildagliptin 50 mg twice daily in a active treatment
controlled, randomised and double blind cross-over design. Active treatment
control will consist of acarbose, starting with 50 mg three times a day during
one week and step-up to 100 mg three times a day for the remaining three weeks.
The wash out period will be one week.
Study burden and risks
Vildagliptin is used in the treatment of type 2 diabetes and is well tolerated.
Side effects like headache, dizziness and nausea can occur. There is a small
risk for participants to develop hypoglycaemia when vildagliptin is added to
their medication. We can expect patients with type 2 diabetes to anticipate on
hypoglycaemia by eating. Prior to the start of the trial participants will be
informed on these potential risks of the trial and given instructions on how to
take action on them.
Acarbose is registered for the treatment of type 2 diabetes and can induce
gastrointestinal side effects, which completely resolves after withdrawal.
Plethysmography will cause numbness and discomfort in both hands due to
inflation of the wrist cuffs. This is temporarily and completely reversible.
Finally, bruising may occur after venapuncture or removal of the intra-arterial
20 G cannule. Measure like pressure bandages will be taken to minimise the
risk.
After subcutaneous fat biopsy bruising may occur.
The subjects will not benefit directly from participating in this study.
Geert Grooteplein Zuid 8
6500 HB Nijmegen
NL
Geert Grooteplein Zuid 8
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
- type 2 diabetes
- age 35-75 years
- metformin monotherapy or combination therapy
- HbA1c < 8.0%
Exclusion criteria
- Renal disease defined as creatinine level > 130 umol/l
- Liver disease defined as aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range
- Current use of acetylsalicylic acid or vitamine K antagonists
- History of smoking within the past year
- History of or current abuse of drugs or alcohol
- History of heartfailure (NYHA class III or IV)
- Abnormalities on ECG that might interfere with current study protocol
- Pregnancy or breastfeeding
- Inability to understand the nature and extent of the trial and procedures required
- Presence of any medical condition that might interfere with the current study protocol
- Participation in a drug trial within 60 days prior to the first dose
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov, nog geen nummer bekend |
| EudraCT | EUCTR2009-016053-18-NL |
| CCMO | NL29747.091.09 |