The primary objective of this study is to determine whether ACE inhibition results in an improvement of microvascular glycocalyx-thickness in patients with type 1 diabetes. The secondary objectives are to investigate whether this (hypothesized)…
ID
Source
Brief title
Condition
- Diabetic complications
- Nephropathies
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary parameter of the study is the change in microvascular glycocalyx
thickness before and after treatment with lisinopril and placebo.
Secondary outcome
The secondary parameters of the study are change in blood pressure,
microalbuminuria, glomerular charge selectivity, plasmalevels of hyaluronan,
hyaluronidase,vWf and prothrombin fragment 1+2, VCAM-1 and ICAM-1 and change in
15(S)-8-iso-prostaglandin levels in 24 hours urine samples.
Background summary
Microalbuminuria in diabetes mellitus is not only associated with progression
to renal disease, it is also a potent predictor of cardiovascular disease and
thus may reflect widespread vascular damage. Endothelial dysfunction is one of
the first steps in the development of vascular damage, and is commonly found in
patients with microalbuminuria. The endothelium is covered by the endothelial
glycocalyx. In patients with type 1 diabetes a significant reduction of its
systemic volume and microvascular thickness was found. This reduction was even
more profound in patients with microalbuminuria.
Ace-inhibitors have a positive effect on microalbuminuria in diabetic patients
and on endothalial function. This might be caused by a direct effect on the
glycocalyx.
Study objective
The primary objective of this study is to determine whether ACE inhibition
results in an improvement of microvascular glycocalyx-thickness in patients
with type 1 diabetes. The secondary objectives are to investigate whether this
(hypothesized) improvement correlates with a decrease in microalbuminuria as
well as glomerular charge selectivity and whether the improvement can be
explained by an amelioration of the oxidative or inflammatory state in these
patients.
Study design
Double-blind, randomized placebo-controlled crossover study.
Intervention
All included subjects will be randomly treated with either placebo or
lisinopril 20 mg for two weeks, followed by a two week washout period. After
the washout period, the subjects who received placebo in the first treatment
period will receive lisinopril for two weeks and vice versa. The total study
period will amount to six weeks for all included subjects.
Study burden and risks
Included subjects will visit the AMC hospital five times:
Visit 1: Screening visit, informed consent, medical history and vital signs.
Visit 2: Orthogonal polarization spectral (OPS) imaging of the sublingual
microcirculation, laboratory measurements and collect urine, start study
medication A.
Visit 3: OPS imaging of the sublingual microcirculation, laboratory
measurements and collect urine, start washout period.
Visit 4: OPS imaging of the sublingual microcirculation, laboratory
measurements and collect urine, start study medication B.
Visit 5: OPS imaging of the sublingual microcirculation laboratory measurements
and collect urine, end of study.
Burden for the patient: At all visits approximately 20 ml of blood will be
drawn, OPS imaging is non-invasive and painless.
Meibergdreef 9
1105 AZ Amsterdam
Nederland
Meibergdreef 9
1105 AZ Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
Caucasian
Male
Diagnosis of type 1 diabetes according to ADA criteria
Urinary albumin/creatinin ratio <3,5 mg/mmol, without antiproteinuric treatment
Exclusion criteria
Hypertension as defined by systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg or use of antihypertensive drugs
Previous use of RAS inhibitors
Smoking
Primary dyslipidemia*s
Use of statins during the six weeks before visit 1
Use of antioxidants in the two weeks prior to visit 1
Angioedema in medical history
Hypersensitivity to Ace inhibitors
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 |
|---|---|
| EudraCT | EUCTR2008-002610-21-NL |
| CCMO | NL23244.018.08 |