The primary objective of this study is to investigate the effect of 26 weeks of supplementation with three different dietary fibres (chicory inulin, resistant dextrin, and seaweed polysaccharide) compared to a placebo (maltodextrin) on microbiota…
ID
Source
Brief title
Condition
- Mental impairment disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameters are baseline (before week 1) and follow-up (after
week 26) measures of
(1) BOLD signal activity and task accuracy during n-back task fMRI.
Secondary outcome
The secondary study parameters include
(1) Neuropsychological test battery (NTB)
(2) Brain health parameters (in plasma): Tryptophan metabolites (indoles);
Aβ1-42/Aβ1-40 ratio; cortisol levels; brain-derived neurotrophic factor (BDNF);
T1/T2 weighted anatomical scans of brain regions of interest- hippocampus,
temporal- and prefrontal cortices.
(3) Gastrointestinal health parameters (plasma and faeces): intestinal barrier
function, faecal microbiota composition (qualitative and quantitative),
intestinal inflammation, intestinal transit time (ITT), short- (SCFA) and
branched chain fatty acid (BCFA) concentrations, faecal water content & pH;
gastrointestinal symptoms questionnaire and Bristol Stool Scale (BSS).
(4) Immune and metabolic markers: inflammatory marker panel, fasting glucose
and insulin, HbA1c, lipogram (LDL, HDL, total cholesterol, triglycerides).
Background summary
Due to the greying of society, a triplication of the number of people with
dementia worldwide, with Alzheimer*s disease (AD) as the commonest form, is
expected by 2050. Compelling evidence points towards a crucial role of
intestinal health as one potential etiological modifier of dementia, with the
(microbiota) gut-brain axis (MGBA) receiving increasing attention. A number of
preclinical studies have demonstrated benefit of various sources of dietary
fibre for their capacity to improve gut health, cognitive functioning, general
mood, glycaemia, immunogenicity, and, to inhibit tau phosphorylation, the
latter which is a hallmark in AD brain. The proposed mechanism of dietary
fibres is by changing gut microbiota and its metabolites, thereby having
effects on the gut-brain axis and other health parameters.
Subjective cognitive decline (SCD) lies on the continuum of AD, and subjects
with this condition are at increased risk of further conversion to mild
cognitive impairment (MCI) or AD. Currently, no cure is available for AD.
Various symptomatic and a few disease-modifying treatments are available, but
these treatments only have very limited or mild clinical effects and are often
accompanied by severe side effects.
Clinical follow-up studies to evaluate the effect of dietary fibre in older
adults with suspected cognitive decline are required, but are still lacking to
date.
Study objective
The primary objective of this study is to investigate the effect of 26 weeks of
supplementation with three different dietary fibres (chicory inulin, resistant
dextrin, and seaweed polysaccharide) compared to a placebo (maltodextrin) on
microbiota gut-brain health effects in older adults (aged 60-79) with
Subjective Cognitive Decline Plus (SCD+) by assessing changes in brain function
and working memory by blood oxygen level dependant (BOLD) signal activity and
task accuracy during n-back task functional magnetic resonance imaging (fMRI)
assessment.
The secondary objectives are to investigate the effects of 26 weeks of
supplementation with dietary fibre (chicory inulin, resistant dextrin, and,
seaweed polysaccharide) compared to placebo (maltodextrin) in older adults on
the following parameters related to potential gut-brain pathways: (1)
neuropsychological test battery scoring, (2) other relevant brain health
parameters, (3) other relevant intestinal health parameters, and (4) immune and
metabolic parameters.
Study design
Randomised, double-blinded, placebo-controlled intervention study with parallel
design and four arms.
Intervention
To investigate the effects of the 26 weeks of supplementation of the dietary
fibres on the primary and secondary outcomes, four study arms - three
interventions and one placebo- are applied, with different dosages modified to
each individual fibre's tolerance level and expected mechanism(s) of action:
1. Placebo (Maltodextrin) (7g per day, divided over two dosages)
2. Chicory inulin - (12g per day, divided over two dosages)
3. Resistant dextrin - (14g per day, divided over two dosages)
4. Seaweed polysaccharide - (1g per day, divided over two dosages). Will
additionally contain 7g/day of placebo as a volumetric and isocaloric filler.
Study burden and risks
Participants in the three intervention arms will receive dietary fibre twice a
day. Dosages have been evaluated and have no expected side effects, except
possible mild gastrointestinal symptoms/discomfort that should improve with
time. To prevent potential gastrointestinal discomfort, dosage will be tapered
up over a one-week period. The use of dietary fibre is considered safe. For two
periods of seven days at baseline and at follow-up, participants will be asked
to wear a Samsung 2.0 Smartwatch to measure heart rate, physical activity, and
mood. The wearable sensor can be worn while participants lead a regular
lifestyle, and although the watch can cause slight discomfort after prolonged
wearing (like a regular watch), it can be taken off (for a limited time) when
uncomfortable.
An additional burden is the five study visits with multiple outcome assessments
that will take place at Wageningen University and Gelderse Vallei Hospital
(Ziekenhuis Gelderse Vallei) at baseline (before week 1) and follow-up (after
week 26) including neuropsychological testing, MRI-scanning, blood drawing and
faeces and urine sample collection, and clinical measurements. At mid-study
(week 13) participants will visit Wageningen University only for
neuropsychological testing, blood collection and clinical measurements. MRI
scanning might cause mild discomfort (due to loud noises and lying down for 30
minutes), but precautions will be taken to make participants as comfortable as
possible (including earplugs and cushions). Drawing blood samples might cause
mild pain and sometimes bruising, which will usually fade on its own.
Subjective cognitive decline plus is a predecessor stage of AD, but at which
stage the cognitive decline can still be reversed. Thereby a substantial health
benefit can still be gained. In fact, SCD+ represents a sensitive at-risk
population, especially with the inclusion of extra lifestyle for brain health
(LIBRA) factors, which makes it an ideal fit for our study. To the best of our
knowledge, not a single trial assessing the effects of prebiotic
supplementation in older adults with suspected cognitive decline has been
performed yet nor has one been registered (clinicaltrials.gov).
Helix, Stippeneng 4
Wageningen 6708 WE
NL
Helix, Stippeneng 4
Wageningen 6708 WE
NL
Listed location countries
Age
Inclusion criteria
1. Written informed consent
2. Fluency in Dutch (speaking, reading, writing)
3. Age between 60-79 years (at screening)
4. Subjective cognitive decline plus (SCD+), (criteria of Jessen et al. 99):
4.1 Self-reported worsening of memory;
4.2 Indication of repetitive concerns (worries) associated with SCD;
4.3 With at least one of the following two features present:
(i) onset of SCD within the last 5 years;
(ii) age at onset >=60 years of age;
5. Presence of self-reported risk factors for cognitive decline based on the
weighted LIBRA criteria:
at least 2 modifiable risk factors need to be present:
(i) Diabetes mellitus type II 1 (has your doctor ever told you that you have
diabetes yes/no)
(ii) High cholesterol 1 (has your doctor ever told you your cholesterol is too
high yes/no)
(iii) Hypertension 1 (has your doctor ever told you that you have high blood
pressure yes/no)
(iv) High BMI 1,2
(v) Heart disease 1 (has your doctor ever told you that you have a heart or
blood vessel condition)
(vi) Unhealthy diet 1 (lower regular adherence to Mediterranean diet components
such as fish, vegetables, olive oil, pasta
and red wine)
1Criteria defined by the short version questions from LIBRA Administration
2 Defined as >=25 kg/m2 for 60-69 years old, and >=28 kg/m2 for >=70 years old,
based on self-reported height and weight.
Exclusion criteria
1. Current participation in other intervention trials
2.Technologically illiterate (complete incompetence in working with computers,
apps, online questionnaires, smartwatches etc.)
3.No internet access from home
4.Clinical diagnosis of >=1 of the following:
- Neurological pathology (e.g. MCI, dementia, multiple sclerosis, Parkinson*s
disease, epilepsy);
- Current malignant disease(s), with or without treatment;
- Current psychiatric disorder(s) (e.g. major depressive disorder, bipolar
disorder, schizophrenia, psychosis, anxiety, posttraumatic stress disorder);
- Symptomatic/decompensated cardiovascular disease (e.g. stroke, angina
pectoris, heart failure, recent myocardial infarction);
- Severe visual impairment or blindness
- Hearing or communicative impairment.
- Gastrointestinal tract disorder such as irritable bowel syndrome or
inflammatory bowel disease (e.g. Chron*s disease or ulcerative colitis).
5. Current or recent (<6 weeks) use of prebiotic, probiotic, or dietary fibre
supplement that may modulate the microbiota, or unwilling to stop the use of
supplements during the study
6. Current or recent (<6 weeks) of algae/phytoplankton supplements such as
spirulina or chlorella, or unwilling to stop the use of supplements during the
study
7. Use of psychotropic medication (anti-depressants, anti-psychotics)
8. Use of antibiotics in the 3 months before starting the study or planned use
during the study
9. Being an employee of the Human Nutrition and Health Division of Wageningen
University.
10. Significant cognitive impairment assessed using the Modified Telephone
Interview for Cognitive Status battery (TICS-m score <23)
11. Request to have Apo-E genotype result disclosed
12. Allergy to fish or shellfish
13. Having a contra-indication to MRI scanning including:
- Ferromagnetic implants:
- Active implantable medical devices such as: insulin pump / medicine pump /
neurostimulator; pacemaker / defibrillator;
- Other passive implants such as: punctured port-a-cath; synthetic heart valve
- Intra-orbital or intra-ocular metallic fragments
- Claustrophobia
14. Any other relevant medical or surgical history that is not mentioned in
above criteria, which could influence the study outcome measurements, as
determined by the researchers.
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 | NL85910.091.23 |