Primary objective:To assess the effects of fenretinide on hepatic and peripheral insulin sensitivity in obese, insulin resistant subjectsSecondary objective:To assess the effects of fenretinide on hepatic steatosis, body weight and body fat…
ID
Source
Brief title
Condition
- Other condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Hepatic and hepatobiliary disorders
Synonym
Health condition
obesitas
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Changes in hepatic and peripheral insulin sensitivity
Secondary outcome
Liver steatosis
Plasma retinol and RBP4 levels
Subcutaneous adipose tissue: concentrations of RBP4 and key proteins involved
in insulin signaling levels
Plasma HPR and its metabolites (MPR, 4-oxo-HPR) levels
Resting energy expenditure (REE) and body fat composition
Glucoregulatory hormones, adipokines and markers of inflammation
Safety and tolerability of HPR/LXS
Background summary
The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing.
Recent studies have provided evidence that retinol binding protein 4 (RBP4) is
involved in the induction of insulin resistance (IR). Fenretinide is a
synthetic retinoid found to lower RBP4 levels. Preliminary data show that it
might improve insulin sensitivity, making it a promising new therapy for IR and
T2DM.
Study objective
Primary objective:
To assess the effects of fenretinide on hepatic and peripheral insulin
sensitivity in obese, insulin resistant subjects
Secondary objective:
To assess the effects of fenretinide on hepatic steatosis, body weight and body
fat composition
To assess changes in RBP4 mRNA and protein levels as well as key proteins in
the insulin signaling cascade in subcutaneous adipose tissue
Study design
Randomized double blind placebo controlled study
Intervention
Treatment arm: HPR/LXS 154 mg QD for 90 days; placebo arm: blank Lym-X-Sorb
matrix (LXS) QD for 90 days
Study burden and risks
Biometric data such as waist circumference, BMI and blood pressure will be
measured. Subjects will visit the research unit several times during the study;
total visit time will be about 26 hours. An MRS of the liver will be performed
to quantify liver fat content. The MRS-scan requires lying still as possible
for 45 minutes. Subjects will undergo a 2-step hyperinsulemic-euglycemic clamp
using stable isotopes before and after the intervention period to study glucose
metabolism. For the administration of the stable isotope, glucose and insulin
and for blood sampling, intravenous canules will be inserted in the left and
right antecubital vein. Stable isotopes are not harmful and hypoglycaemia will
not occur because glucose is monitored every 5 minutes. Total clamping time on
one day will be 7 hours. Fat biopsies, performed before and after the
intervention period, will be used to investigate changes in insulin signalling
pathways as a consequence of changes in insulin resistance. Subcutaneous fat
biopsies will be taken from the periumbilical region and will take
approximately 30 minutes. Biopsies will be preceded by local anesthesia with
lidocain and will only cause minor discomfort.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Post menopausal female
Age 40-65 years
BMI * 30 kg * m-2
HOMA-IR * 2.7
Signed informed consent
Exclusion criteria
T2DM treated with medication other than metformin or sulfonylurea derivates
Any medical condition except for glucose intolerance, T2DM, hypertension and secondary dyslipidemia
Prolonged PTT/aPTT or thrombocytopenia
Retinol levels of < 1.8 uM
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 | EUCTR2011-006165-18-NL |
| CCMO | NL39363.018.12 |