A randomized, double-blind, placebo-controlled crossover study to assess the effect of 12-week fibre supplementation on mixed-meal challenge response in adults

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 64

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoints<br /><br>* Microbiome changes measured using 16S rRNA sequencing at baseline and at time<br /><br>points as defined in table 1 and 2.<br /><br>* Response to challenge of metabolic and inflammatory biomarkers including but<br /><br>not limited to non-esterified fatty acids (NEFAs), glucose, insulin,<br /><br>triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein<br /><br>(LDL), total cholesterol, interleukin-6, -8 and -10, tumour necrosis factor<br /><br>alpha (TNF-*), high-sensitivity C-reactive protein (hs-CRP), serum amyloid A<br /><br>(SAA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and<br /><br>gamma-glutamyltransferase (GGT).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints<br /><br>* Baseline and post-intervention metabolic and inflammatory biomarkers<br /><br>including but not limited to NEFAs, glucose, insulin, TG, HDL, LDL, total<br /><br>cholesterol, interleukin-6, -8 and -10, TNF-, hs-CRP, SAA, ALT, AST and GGT.<br /><br> In vitro culturing of stool through the TNO I-screen platform and faecal SCFA<br /><br>content at baseline and before the second treatment period.</p><br>