Primary ObjectiveTo relate microbiome modulation by dietary fibre supplementation, as measured by 16S rRNA sequencing, to changes in response to a mixed-meal metabolic challenge (PhenFlex) as measured by composite biomarker score.Secondary…
ID
Source
Brief title
Condition
- Other condition
- Immune disorders NEC
- Metabolism disorders NEC
Synonym
Health condition
Health status
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints
* Microbiome changes measured using 16S rRNA sequencing at baseline and at time
points as defined in table 1 and 2.
* Response to challenge of metabolic and inflammatory biomarkers including but
not limited to non-esterified fatty acids (NEFAs), glucose, insulin,
triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein
(LDL), total cholesterol, interleukin-6, -8 and -10, tumour necrosis factor
alpha (TNF-*), high-sensitivity C-reactive protein (hs-CRP), serum amyloid A
(SAA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and
gamma-glutamyltransferase (GGT).
Secondary outcome
Secondary endpoints
* Baseline and post-intervention metabolic and inflammatory biomarkers
including but not limited to NEFAs, glucose, insulin, TG, HDL, LDL, total
cholesterol, interleukin-6, -8 and -10, TNF-*, hs-CRP, SAA, ALT, AST and GGT.
* In vitro culturing of stool through the TNO I-screen platform and faecal SCFA
content at baseline and before the second treatment period.
Background summary
Improving healthy physiological processes through nutritional intervention, as
opposed to restoring physiology after disease occurrence, is an important new
avenue for the reduction of disease burden in the population. A relatively new
target for interventions is the gut microbiome. Although the role of the human
microbiome in health and disease is widely acknowledged, specific physiological
mechanisms through which it can affect human health and disease have yet to be
fully elucidated.
Study objective
Primary Objective
To relate microbiome modulation by dietary fibre supplementation, as measured
by 16S rRNA sequencing, to changes in response to a mixed-meal metabolic
challenge (PhenFlex) as measured by composite biomarker score.
Secondary Objectives
To investigate whether results of in vitro microbiome culturing on the I-screen
platform are comparable to in vivo 16S rRNA sequencing and are affected by
fibre supplementation.
To investigate whether fibre supplementation affects basal metabolic and
inflammatory biomarkers and their response to mixed-meal metabolic challenge.
Exploratory Objectives
To investigate the effect of dietary fibre on mood, general health and health
perception.
To investigate whether fibre supplementation affects basal endothelial function
and response of endothelial function to mixed-meal metabolic challenge.
To investigate the relation between oral microbiome and gut microbiome, and the
effects of mixed meal challenge on the oral microbiome.
To investigate the relationship between B cell subsets and gut microbiome
function and modulation.
To investigate the effect of mixed-meal metabolic challenge on biomarkers of
cellular stress.
To investigate the effect of mixed-meal metabolic challenge on
electrocardiographic indices.
Study design
A randomized, double blind, placebo-controlled crossover study with 12-week
treatment periods separated by 8 weeks of washout. Mixed meal challenge tests
will be conducted before and at the end of both treatment periods. The first 20
subjects included (1:1 randomized over treatment arms) will have additional
endothelial testing at baseline and during PhenFlex challenges. Baseline
microbiome analysis will be conducted before both treatment periods, and during
treatment and washout periods subjects will send faecal samples taken at home
to CHDR. 4 follow-up phone calls at week 4, 8, 24 and 28 will be conducted for
questionnaires and adverse event monitoring. End of study will be after the
final mixed-meal challenge at the end of the second treatment period.
Intervention
Investigational fibre mixture (active treatment)
The study product is a fibre mixture consisting of a mix of 10 g of Acacia Gum
(AG) and 3 g of carrot fibre (KaroPRO) taken p.o. o.d. in powder form for a
total of approximately 10 g of dietary fibre per day.
Comparative drug (placebo)
Powder consisting of 13 g of digestible carbohydrates with taste and colour
indistinguishable from investigational fibre mixture.
Study burden and risks
The risk associated with the administration of a combination of AG and KaroPRO
in humans are considered to be negligible, since no toxic effects of dietary
fibre intake have been observed and the components of both ingredients are part
of the normal human diet in similar or higher doses. Side-effects of high
dietary fibre intake are increased intestinal gas production inducing bloating,
as well as an increase in number of bowel movements.
The fibre mixture is expected to have microbiome-changing potential and induce
changes in production of bacterial metabolites. Any observed modulation of
physiological processes in the test subjects is expected to be subtle, since
dosage will not exceed the minimum recommended intake of dietary fibre in the
general population. Among the health benefits from dietary fibre intake
recognised by various food safety agencies such as the FDA and EFSA are
postprandial blood glucose attenuation, postprandial blood cholesterol
attenuation and improved laxation. We expect that participating volunteers will
benefit from increased consumption of the fibres within the context of this
study. Effects of dietary fibre supplementation are reversible, with return to
baseline occurring as early as 3 weeks after intervention in some studies.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Signed informed consent prior to any study-mandated procedure.
2. Healthy male or female subjects, between 45 and 70 years of age, inclusive.
3. Female subjects must be of non-childbearing potential (postmenopausal for at
least 12 months prior to screening or documented surgically sterile).
4. BMI 25-30 kg/m2
5. Fibre intake below recommended limits as assessed by dietary fibre intake
short food frequency questionnaire (DFI-FFQ).
6. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.
Exclusion criteria
1. Evidence of any active or chronic disease or condition that could interfere
with, or for which the treatment of might interfere with, the conduct of the
study, or that would pose an unacceptable risk to the subject in the opinion of
the investigator (following a detailed medical history, physical examination,
vital signs (systolic and diastolic blood pressure, pulse rate, body
temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the
normal range may be accepted, if judged by the Investigator to have no clinical
relevance.
2. Chronic diseases that can affect study parameters, including but not limited
to metabolic syndrome, chronic obstructive pulmonary disease, diabetes
mellitus, auto-immune disease, cardiovascular disease, cerebrovascular disease,
gastrointestinal disease or history of abdominal surgery with removal of (part
of) small or large intestine, or any known condition that can interfere with
treatment compliance such as psychiatric disease or drug dependence.
3. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus antibody (HIV Ab) at screening.
4. Systolic blood pressure (SBP) greater than 180 or less than 90 mm Hg, and
diastolic blood pressure (DBP) greater than 120 or less than 50 mm Hg at
screening.
5. Abnormal findings in the resting ECG at screening defined as:
a. QTcF> 450 for males or QTcF>470 for females or QTcF < 300 ms;
b. Personal or family history of congenital long QT syndrome or sudden death;
c. Evidence of atrial fibrillation, atrial flutter, complete branch block,
Wolf-Parkinson-White Syndrome, or history of cardiac pacemaker.
6. Use of antibiotics, antacids, laxatives, statins, anti-diarrheal,
immunomodulatory or antidiabetic medication <3 months before start of study.
7. Use of any medication or vitamin, mineral, herbal, and dietary supplements
within 7 days of study product administration, or less than 5 half-lives
(whichever is longer). Exceptions will only be made if the rationale is clearly
documented by the investigator.
8. Vegan, macrobiotic, slimming or medically prescribed diet up to 3 months
prior to the first administration.
9. History of food allergies or intolerances or any confirmed significant
allergic reactions (urticarial or anaphylaxis) against any drug or multiple
documented drug allergies.
10. Participation in an investigational drug or device study within 3 months
prior to first dosing.
11. History of abuse of addictive substances (alcohol, illegal substances) or
current use of more than 21 units alcohol per week, drug abuse, or regular user
of sedatives, hypnotics, tranquillisers, or any other addictive agent, or
positive test for drugs of abuse at screening or pre-dose.
12. Active smoker up to 15 years prior to the screening visit.
13. Loss or donation of blood over 500 mL within three months (males) or four
months (females) prior to screening or intention to donate blood or blood
products during the study.
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 | NL71723.056.19 |