Evaluate pharmacokinetic levels of imidazole propionate (ImP) as a result of orally administrated histidine and assess the role of the gut microbiota in this respect, in Type 2 diabetes (T2D) from Dutch and South Asian Surinamese descent as compared…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective will be determination of ImP levels after histidine intake
and other degradation products such as urocanate and glutamate before and after
oral antibiotics.
Secondary outcome
Secondary objectives will be differences in histidine uptake effect upon oral
histidine supplementation on PBMC inflammatory status, influence of gut
microbiome on ImP production, continuous (freestyle libre) as well as
postprandial (after a mixed meal test) glucose levels between healthy and T2D
subjects on stable dose of oral metformin. Furthermore, we will evalualte if
the kinetics and other mentioned parameters are affected differently between
ethnicities by histidine intake.
Background summary
The gut microbiota plays a pivotal role in the pathophysiology of
cardio-metabolic diseases (CMD), such as T2D, obesity and atherosclerosis. The
diet shapes the gut microbiota which can further transform dietary food items
into circulating metabolites, which acts on the host. Among them, Imidazole
propionate (ImP) has recently been discovered. In vitro and mouse experiments
demonstrated that ImP originate from histidine metabolization by the gut
microbiota. Furthermore, ImP is increased in T2D individuals as compared to
healthy controls and induces glucose intolerance in mice. In this study we aim
to confirm in humans that ImP indeed derives from gut microbiota processing of
oral histidine intake. In addition to this, the composition of the mircobiome
has been shown to be different between ethnicities, particularly between
individuals from Dutch or South Asian Surinamese descent. Therefore, we also
want to evaluate of histidine kineticsc and other relevant parameters are
different between these two ethnicities. Furthermore, we aim to evaluate ImP
concentrations after an oral challenge and demonstrate that it differs between
T2D and controls.
Study objective
Evaluate pharmacokinetic levels of imidazole propionate (ImP) as a result of
orally administrated histidine and assess the role of the gut microbiota in
this respect, in Type 2 diabetes (T2D) from Dutch and South Asian Surinamese
descent as compared to healthy controls from the same ethnicities.
Study design
Interventional controlled single centre study
Intervention
We will orally administrate 4g of the food supplement histidine (Vital Cell
Life L-Histidine 500 MG Capsules 100CP) once a day for 7 weeks, after the first
2 weeks, one week of antibiotics will be added to suppress the gut microbiome
followed by a four weeks recovery period. Plasma and urinary ImP, histidine,
urocanate and glutamate levels will be measured as well as, peripheral blood
monocyte cells (PBMC) for inflammatory status will be measured at specific time
points.
Study burden and risks
Subjects will visit the AMC for the screening and then eight times. They will
orally take the food supplement histidine for 7 weeks and antibiotics (for 7
days). Blood samples will be taken at different time points, with a total
amount of 464 ml in total over 7 weeks. Also 24h urine and 24h feces will be
collected at four visits and subjects are asked to monitor their dietary intake
during the study days. Two days after starting with antibiotics, individuals
will be asked to freeze their feces at home and bring it to the next study
visit. In a previous study higher dosages of the food supplement histidine were
given without any adverse effecte, therefore, in this study we do not expect
any adverse effect of histidine use.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Healthy subjects: (n=11 Caucasian and n=11 from South Asian Surinamese descent)
- Healthy subjects 40-70 years,
- BMI 19-25
T2D subjects:(n=11 Caucasian and n=11 from South Asian Surinamese descent)
- T2D patients
- Caucasian / South Asian Surinamese
- 40-70 years
- BMI 25-35
- Stable anti-diabetic drugs for 3 months (metformin is obligatory)
- Statin use
- Stable medication use past 3 months
- Able to give informed consent
Exclusion criteria
All participants:
- Previous major cardiovascular event (e.g. AMI/stroke/TIA)
- Proton-pomp inhibitor use
- GLP1 or insulin
- Antibiotics use for the past 3 months
- Probiotic of symbiotic usage
- Pregnant women,
- Chronic illness (including a known history of heart failure, renal failure
(eGFR <30 ml/min), pulmonary disease, gastrointestinal disorders, or
hematologic diseases), or other inflammatory diseases
- Active infection,
- Previous intestinal (e.g., bowel resection/reconstruction) surgery
- Smoking
- Vegetarian diet
- >6 alcohol units per day or >14 alcohol units per week
- Active malignancy
- HbA1c >9% (75mmol/mol)
- The subject is already involved in a clinical trial
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 | NL71957.018.19 |