Clinical Trial Details
— Status: Suspended
Administrative data
| NCT number |
NCT04124016 |
| Other study ID # |
796/2018/SPER/UNIPR |
| Secondary ID |
|
| Status |
Suspended |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 2, 2019 |
| Est. completion date |
December 27, 2022 |
Study information
| Verified date |
April 2021 |
| Source |
University of Parma |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Flavan-3-ols are the main source of flavonoids in Western diets. They are characteristic
compounds of tea, cocoa, wine, apple, pears, etc. In plant-based foods, they occur as simple
monomers or as oligomers and polymers of up to 50 units (also known as proanthocyanidins or
condensed tannins). When ingested, both monomeric and high molecular weight flavan-3-ols are
poorly absorbed and metabolized in the first gastrointestinal tract, reaching the colon and
becoming a suitable substrate for the local microbiota. These compounds undergo an extensive
microbial metabolism leading to the formation of hydroxyphenyl-γ- valerolactones (PVLs),
which are then absorbed by colonocytes before reaching the liver and being converted into
phase II conjugated metabolites. Since the microbiota composition varies among individuals,
it results in differences in the production of PVLs and, consequently, the health effects of
flavan-3-ols might change at an individual level.
Another factor of variability might be due to a different asset in the fermentation of
indigestible dietary carbohydrates, which are known to modify colonic pH through the
production of short-chain fatty acids and may result in different profiles of gas production
(i.e. hydrogen and methane), possibly affecting the bioconversion of flavan-3-ols as well.
Nevertheless, these multiple variabilities are poorly understood to date.
Description:
The study will be a single-dose, partially randomized, cross-over design, with 4 consecutive
treatments. The study includes 4 phases where each volunteer will consume a specific dose of
one of the products chosen for the study. Each volunteer will consume each product once, for
a total of 4 different occasions. The products will be a food extract consisting of chicory
fermentable fiber (inulin) fractions followed by three food extracts rich in a different type
of flavan-3-ols, consumed at three different occasions and in random order.
Volunteers will be asked to provide once a fecal sample, taken from the first daily
defecation, which will be analyzed for fecal microbiota composition. They will also undergo a
Breath gases day profile in order to evaluate the effect of inulin consumption on colonic
fermentation and breath-gases production. These two analyses (fecal samples microbial
composition and breath-gases production) will serve to characterize the volunteers' gut
microbiota composition and functionality. In detail, during the 48-h before the fecal and
breath samples collections, volunteers will be asked to avoid a high level of fiber and
(poly)phenols (to facilitate adherence to the dietary restrictions, a list of permitted and
forbidden foods will be supplied. To check dietary compliance, a 2- days dietary record of
the 2 days prior to each sampling day will be used.
The morning of the first treatment, volunteers will arrive, after an overnight fast, and they
will deliver the fresh fecal sample. After that, one sample of forced end-expiratory samples
of alveolar air will be collected. Then, they will be given a standardized test breakfast
consisting of 12 g of food extract of chicory inulin fractions dissolved into 250 g water and
a fermentable fiber-free, (poly)phenol-free, nutritionally-balanced solid meal. They will be
asked to consume the entire breakfast within 15 minutes. At hourly intervals for 11 hours
after breakfast, forced end-expiratory samples of alveolar air will be collected. During the
whole test, all subjects will refrain from smoking, sleeping, exercising and eating foods or
meals other than the ones provided by the staff. Five hours after starting the test,
volunteers will eat a fermentable fiber-free nutritionally-balanced standardized lunch
provided by the study staff.
Subsequently, on three distinct occasions and with one-week wash-out between different
treatments, each participant will randomly consume a dose of flavan-3-ol rich extracts. Each
test day, participants, after fasting baseline urine collection, will receive the dose of one
of the food extract rich in flavan-3-ols (1 mmol of PVL precursors) dissolved into 200 mL of
water. Then, the same standardized breakfast (pre-packaged (poly)phenol-free snack) will be
provided to subjects. After breakfast, volunteers will be allowed to leave and to perform the
successive urine collections on their own. Urine samples will be collected at selected
intervals of time along the 24 h following the extract ingestion. In addition, urine sampling
will continue in a subgroup of volunteers for the successive 24 h to evaluate the evolution
of metabotypes from 24 to 48h. This subgroup will be composed of the first 30 participants
enrolled in the study.
Subjects will be asked to follow a (poly)phenol-poor diet 48-h before each test day and while
sampling (to facilitate adherence to the dietary restrictions, a list of permitted and
forbidden foods will be supplied; to check dietary compliance, a 3/4-days dietary record of
the 2 days prior to each sampling day and of the sampling day(s), depending on the subgroup
the subject belongs to, will be used.
At the end of all treatments, and on the basis of the results of gas samples analysis, one
subgroup of methane producer volunteers (number=5) and one of non-methane producers
(numnber=5) will be asked to provide one further faecal sample, taken from the first daily
defecation for In Vitro analysis of short-chain fatty acids and gas production after
incubation with different mixes of Inulin and Polyphenols used during the In Vivo part of the
study . Volunteers will be asked to follow a diet poor in (poly)phenols and fermentable fiber
for 2 days before fecal donation.
