To study the pharmacokinetics of non-reactive labelled histidine (L-HISTIDINE:HCL:H2O (D5, 98%; 15N3,98%) and the effect on intestinal imidazole propionate (IP)production in small intestine vs colon in healthy controls, metabolic syndrome and DM2…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Metabolism disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective will be determination of plasma and 24h fecal concentrations
of labelled L-histidine and its degradation products, urocanate, IP and
glutamate upon either ingestion of gelatin capsules (thus small intestinal
release) or colopulse capsules (colonic release).
Secondary outcome
Secondary objective will be differences in uptake and production between
subjects with a normal and impaired insulin sensitivity as well as in DM2
subjects on stable dose of oral metformin in relation to fecal microbiota
composition.
Background summary
The prevalence of type 2 diabetes mellitus (DM2) remains alarmingly high.
Mounting evidence links the human intestinal microbiota (bacteria) as well as
their produced metabolites to the development of cardiometabolic diseases,
including DM2. A recent study identified a new microbiota-derived amino acid on
glucose metabolism. We found that the microbially upregulated histidine-derived
metabolite imidazole propionate (IP) may contribute to the pathogenesis of type
2 diabetes (DM2). But the interventional part of this study was performed in
mice and in vitro only. Therefore, in the current pilot study we aim to further
unravel the role of this IP in the human metabolism by first studying the
pharmacokinetics of labeled histidine and the pathway leading to IP in
different parts of the intestine in subjects with a normal en impaired glucose
tolerance (metabolic syndrome and DM2).
Study objective
To study the pharmacokinetics of non-reactive labelled histidine
(L-HISTIDINE:HCL:H2O (D5, 98%; 15N3,98%) and the effect on intestinal imidazole
propionate (IP)production in small intestine vs colon in healthy controls,
metabolic syndrome and DM2 subjects
Study design
Interventional controlled single centre pilot study
Intervention
We will orally administrate labelled histidine twice (either using gelatin
capsules that are releasing histidine in the small intestine versus
ColoPulse-capsules that release histidine in the colon) and subsequently
measure histidine, urocanate, IP levels and glutamate levels until 24h after
ingestion.
Study burden and risks
Subjects will visit the AMC for the screening and then four times: for both the
capsules they will come on two consecutive days with a week in between. They
will orally take labelled histidine and blood samples will be taken at
different time points, with an amount of blood taken of 220 ml in total. 24h
urine and 24h feces will be collected twice and subjects are asked to monitor
their dietary intake during the study days.
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
All subjects: age 18-54 years old, caucasian male, able to give informed consent;- Healthy controls: Subjects do not meet the criteria for metabolic syndrome or diabetes type 2, BMI <25 kg/m2
- Metabolic syndrome subjects: at least 3 out of 5 NCEP metabolic syndrome criteria (fasting plasma glucose * 5.6 mmol/l OR HOMA * 2.5, triglycerides * 1.7 mmol/l, waist-circumference > 102 cm, HDL-cholesterol < 1.04 mmol/l, blood pressure * 130/85 mmHg).
- DM2 subjects: must meet the criteria for DM2: a random blood glucose level of >11.1 mmol/L and/or a fasting blood glucose level of >7.0 mmol/L and/or a blood sugar glucose of >11.1mmol/L two hours after an oral glucose toleralance test and/or an HbA1c of >47mmol/mol. Stable metformin use for at least 1 month (preferably 3dd 500mg)
Exclusion criteria
All subjects:
- Cholecystectomy
- A history of cardiovascular event (MI or pacemaker implantation)
- Use of medication in the last three months with the exception of metformin for DM2 subjects
- (expected) prolonged compromised immunity (due to recent cytotoxic chemotherapy or HIV infection with a CD4 count < 240).
- Smoking, drugs- or alcohol abuse
Design
Recruitment
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 |
|---|---|
| CCMO | NL61849.018.17 |