To investigate the effects of colesevelam (bile acid sequestrant) on bile acid composition, glucose metabolism and composition of faecal flora in patients with an impaired glucose tolerance or newly diagnosed type 2 diabetes
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints are changes in bile acid composition
Secondary outcome
Secondary endpoints are changes in hepatic and peripheral insulin resistance
(assessed by hyperinsulinemic euglycemic clamp and stable isotopes at baseline
and after 12 weeks), metabolic parameters (lipid profile, glycemic control) as
well as changes in faecal microbiota, glucose and lipid content (assessed by
analysing faeces samples). Finally, muscle and adipose tissue samples will be
obtained to assess D2 mRNA and activity and phosphorylation status of the
insulin signalling cascade.
Background summary
Colesevelam is a bile acid sequestrant that has been approved for use as a
cholesterol-lowering agent. Surprisingly, treatment with colesevelam not only
improves lipid parameters, but also improves glycemic control in patients with
type 2 diabetes, with a reduction in HbA1c of 0,5 % and a concomitant decrease
in postprandial plasma glucose values. The exact mechanisms behind these
glucose lowering effects remain unclear; however they are likely
multifactorial.
Study objective
To investigate the effects of colesevelam (bile acid sequestrant) on bile acid
composition, glucose metabolism and composition of faecal flora in patients
with an impaired glucose tolerance or newly diagnosed type 2 diabetes
Study design
Double blind randomized controlled single center trial
Intervention
Patients will be randomised to either colesevelam treatment or placebo
treatment for a period of 12 weeks
Study burden and risks
Stable isotopes are harmless. Muscle biopsies and fat aspirate can cause
hematoma: a minimal invasive biopsy and pressure bandage are used in order to
minimalize this risk. Patients can however experience a bruising feeling.
During clamp, insulin is infused at 20-60 mU per m2 per minute. Insulin
infusion involved the risk of a hypoglykemia. In order to compensate for the
insulin infusion, glucose 20% is infused to maintain blood sugar levels between
5 and 5.5 mmol/l. The rate of glucose infusion is determined by checking the
blood sugar levels every 5 to 10 minutes.
Meibergdreef 9
1100 DD Amsterdam
NL
Meibergdreef 9
1100 DD Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Male subjects with an impaired fasting glucose or newly diagnosed type 2 diabetes (fasting plasma glucose> 6.0), 18 to 55 years-old and body mass index (BMI) >30 kg/m2.
Exclusion criteria
- Patients with medication known to interfere with glucose metabolism or gut microbiota composition (antibiotics, sequestrants, chenodiole, ursochol)
- Patients with severe hypertriglyceridemia or any other primary lipid disorder.
- Patients who practice intensive sports (>three times weekly endurance exercise)
- Patients with thyroid diseases (TSH is measured at screening)
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 | EUCTR2009-011972-31-NL |
| CCMO | NL27774.018.09 |
| Other | NTR-5545 |