Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03710850 |
Other study ID # |
NV18-01-00040 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
May 1, 2018 |
Est. completion date |
March 30, 2021 |
Study information
Verified date |
March 2022 |
Source |
Charles University, Czech Republic |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Gut microbiota may play a key role in many metabolic diseases, including type 2 diabetes
(T2D). Consumption of high-fat/high-sugar western diet seem to alter human resident
microbiota towards reduced genetic diversity and to influence its metabolic activity towards
enhanced energy extraction. Plant-based diets are effective in the treatment of T2D but it is
not clear whether their effect results solely from diet composition or whether it is
mediated, at least partly, by different microbiota and its metabolic activity. One possible
therapeutic approach is replacement of "pro-diabetic" microbiota with its "healthy" variant
but what the "healthy" microbiota is and under which conditions this microbiota could stay
stable and functional is not known. The aim of the proposed study is to identify possible
metagenome/metabolome characteristics in different human cohorts (T2D vs vegans), to assess
the stability of vegan microbiota in T2D-like environment and to evaluate the possibility to
influence human T2D microbiota/metabolome towards more protective composition by dietary
intervention.
Description:
The aim of this project is to study the possibilities of gut microbiota manipulation in type
2 diabetes (T2D) towards more beneficial genetic and metabolic profile. This study address
several issues. First, identification of specific metagenome/metabolome features
characteristic for human cohorts with different risk of T2D development. Second, the
resilience of microbiota associated with beneficial metabolic phenotype in pro-diabetogenic
environment and the possibility to support its survival by prebiotic treatment. Third,
development of the method for personalized prediction of the effectivity of prebiotic
treatment in T2D patients and the evaluation of the benefit of long-term prebiotic
administration in responders´ subpopulation. The project will be realized in three work
packages.
WP1: Observation study focused on the description of gut microbiome and metabolome in obese
type 2 diabetics, vegans and obese but otherwise healthy omnivores and identification of key
markers specific for these populations.
WP2: Study focused on the interaction of vegan microbiota and pro-diabetogenic (western-type)
diet and on the effects of prebiotic supplementation in germ-free animals. In addition, the
effect of diet-alone and the effect of standardized Schaedler flora will be tested as well.
WP3: The identification of predictive markers indicative for the benefit of prebiotic
treatment in the individual context (T2D cohort) and second, long-term human intervention
study in the selected responders´ group aimed on the possibility of therapeutic modulation of
gut microbiome/ metabolome by prebiotics. Only WP3 is subjected to clinical trial
registration.
In details:
WP 3: Identification of T2D subpopulations according to their susceptibility to dietary fiber
intervention Questions:
1. Are there different subpopulations within T2D subjects that differ in their ability to
increase SCFA production in response to prebiotic supplementation?
2. Is it possible to identify these subpopulations ("responders" vs "non-responders") by
simple intervention test?
3. Is this phenomenon associated with specific microbiota composition?
4. Within "responder" subpopulation, is it possible to manipulate fecal
metabolome/metagenome towards more beneficial composition by long-term prebiotic
intervention? In order to fulfill this task microbiome characterization of T2D cohort in
WP1 will be used.
The aim of WP3 is to provide the proof of concept that a diet enriched with specific
prebiotics improves the specific (SCFA) metabolite production and that the beneficial effect
is dependent on pre-existing microbiota composition.
Acute intervention test ("inulin test") The participants enrolled into T2D cohort will be
asked to participate in short-term intervention test. They will be provided the prebiotic and
instructed on the test procedure.
Step 1: sample the stool ("sample 1"); step 2: take the dose (20 g) of inulin; step 3: during
following three days collect sample of feces at each defecation. The samples will be analyzed
by NMR and mass spectrometry with special respect to SCFA content.
Primary readout: The magnitude of SCFA content elevation after the bolus prebiotic
administration.
Secondary readout: The potential association between the response to prebiotic bolus and
microbiota composition.
Long-term intervention study Based on the results of acute inulin intervention test, the
subgroups of most pronounced "responders" and "non-responders" will be selected (defined as
both extreme tertiles of the group, at least 10 subjects are expected to be enrolled per
subgroup). Participants from both subgroups will be asked to take part in three months
intervention study when they will be administered 10 g of inulin prebiotic (FAN s.r.o.,
Tišice 225, 27715 Tišice) on every-day basis. Prior and at the end of the intervention
period, the participants will be subjected to metabolic characterization, indirect
calorimetry and assessment of intestine permeability. Feces samples will be collected before
the study and then after each month for 16S rRNA sequencing, NMR spectroscopy and mass
spectrometry.
Primary readout:
gut microbiome and fecal, urine and plasma metabolome composition of feces
Secondary readouts:
1. metabolic characteristics: basal blood tests (glucose, lipid profile, NEFA, insulin,
C-peptide); twostep hyperinsulinemic euglycemic clamp; indirect calorimetry with energy
expenditure and respiratory quotient
2. intestinal permeability markers: serum content of bacterial endotoxin, D-lactate,
endotoxin core antibody, iFABP and citrulline.
Expected outcome: validation of short prebiotic intervention test as a tool for prediction of
the efficiency and benefit of long-term prebiotic supplementation; evaluation of the benefit
of long-term prebiotic supplementation in T2D "responder" subgroup.