Clinical trial NCT05675007: Effects of a Colon-delivered Multivitamin Supplement on Brain Functioning, Immunometabolic- and Intestinal Markers in Ageing
Official title: The Effects of a Colon-delivered Multivitamin Supplement on Brain Functioning and Its Relation With Immunometabolic and Intestinal Markers in Ageing: the COMBI Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognitive Decline
Aging
Keywords: Intestinal health
Gut-brain axis
Lead sponsor: Donders Centre for Cognitive Neuroimaging
Sponsor class: OTHER
Collaborators: name: Wageningen University and Research
First posted: 2023-01-09
Enrollment: 75
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This randomized controlled trial has two parallel intervention arms. One group will daily consume a colon-delivered multivitamin supplement for 6 weeks. The other group will daily consume a placebo tablet for 6 weeks. Participants will we randomly assigned to one of the two groups.
Primary purpose: BASIC_SCIENCE

Brief summary: COMBI is a multi-center, randomized controlled trial among 70 older adults at risk of cognitive decline. The main goal is to investigate the effect of a 6-week colon-delivered multivitamin supplementation on the gut-brain axis in older adults, by assessing changes in brain function as well as intestinal changes compared to placebo.

Detailed description: Growing evidence indicates an important role for intestinal health in development of cognitive decline in ageing. Intestinal health, and especially the gut microbiome, is assumed to affect brain health and functioning via immunometabolic pathways captured in the gut-brain axis. However, it is unclear whether changes in intestinal health markers causally relate to cognitive decline in older adults and how. Nutritional interventions specifically targeting the gut were found beneficial for human cognition and brain function. An intervention based on colon-delivered vitamins (B2, B3, B6, B9, C, D3) is proposed to affect gut health using microbiome-dependent and independent pathways. In this study, it will be investigated whether this intervention affects neurocognition in ageing humans, to reveal causal gut-brain relationships in aging.Therefore, the primary goal of the COMBI study is to investigate the effect of a 6-week colon-delivered multivitamin supplementation on the gut-brain axis in older adults, by assessing changes in brain function as well as intestinal changes compared to placebo. Secondary, the effects of this 6-week colon-delivered multivitamin supplementation in older adults on the following parameters related to potential gut-brain pathways will also be investigated: (1) other relevant brain parameters, (2) other relevant intestinal parameters, (3) immunometabolic parameters related to gut-brain pathways, and (4) neuropsychological test battery scoring.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Age between 60-75 years (at pre-screening)
* Fluency in Dutch (speaking, reading and writing)
* Score ≥2 points on the risk factor scale below based on self report:

  * BMI≥25 (1 point)
  * Physical inactivity (according to WHO guidelines) (1 point)
  * Hypertension (1 point)
  * Hypertension without medication (1 point)
  * Hypercholesterolemia (1 point)
  * Diabetes type II (1 point)
  * Mild cardiovascular disease (1 point)

Exclusion Criteria:

* Food allergies or other issues with the vitamins included in the supplement
* Concurrent participation in other intervention trials
* Clinical diagnosis of ≥1 of the following:

  * Stroke;
  * Neurological disease(s) (e.g. MCI, dementia, MS, Parkinson's, epilepsy);
  * Current malignant disease(s), with or without treatment;
  * Current psychiatric disorder(s) (e.g. depression, psychosis, bipolar episodes, eating disorder);
  * Symptomatic cardiovascular disease (e.g. stroke, angina pectoris, heart failure, myocardial infarction);
  * Revascularisation surgery in the last 12 months at pre-screening;
  * Gastrointestinal diseases (i.e., diarrhoea, Crohn's disease, ulcerative colitis, diverticulosis, stomach or duodenal ulcers) or having a history of gastrointestinal surgical events (e.g. stoma) that may influence the results of the study, as determined by the study team;
  * Visual impairment (e.g. blindness);
  * Hearing or communicative impairment.
* Use of antibiotics within the previous 3 months before the study start.
* Use of protonpump inhibitors within the study period (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)
* Not willing to refrain from taking other supplements (containing vitamin B2, B3, B6, B9, or C, prebiotic, or probiotic) that can interfere with the study outcomes, from at least 2 weeks before start of the intervention till the end of the intervention period.
* Answering "Yes" on ≥1 of the Donders Institute MRI safety screening protocol questions (see the 8 questions below):

  1. Are there metal objects located in your upper body? Exception: tooth-fillings and/or dental crowns.
  2. Are there metal splinters in your body, in particular within the eyes? For example: through labour work in the metal industry.
  3. Are there jewellery items or piercings that you are unable to take off?
  4. Have you had a brain surgery in the past?
  5. Are there active implants present? For example: pacemaker, neurostimulator, insulin pump, hearing aid (that is unable to be removed).
  6. Are there any medical plasters or patches that you can't or may not take off? For example: nicotine patch.
  7. Do you suffer from epilepsy?
  8. Do you suffer from claustrophobia?
* Cognitive impairment as determined by Telephone Interview for Cognitive Status (TICS-M1), performed during pre-screening before inclusion and defined as a score \<23.

Primary outcomes:
measure: Change in brain activity during working memory
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in working memory performance
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in faecal short-chain fatty acids
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Secondary outcomes:
measure: Change in brain myo-inositol levels (neuroimaging)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in cerebral perfusion levels (neuroimaging)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in neuropsychological test-battery scoring
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in microbiota profile (faecal)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in individual short-chain fatty acids profile (faecal)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in stool water content (faecal)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in stool pH (faecal)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in stool redox potential (faecal)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in intestinal inflammation profile (faecal)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in C-reactive protein concentration (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in white blood cell count (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in inflammation profile (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in intestinal integrity profile (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in anti-oxidant status profile (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in metabolic profile (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in brain health profile (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in vitamin profile (blood)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Other outcomes:
measure: Body mass index
timeFrame: Baseline (T0)
measure: Waist circumference
timeFrame: Baseline (T0)
measure: Hip circumference
timeFrame: Baseline (T0)
measure: Blood pressure
timeFrame: Baseline (T0)
measure: Abdominal fat distribution
timeFrame: Baseline (T0)
measure: Baseline Demographics and medical history (questionnaire)
timeFrame: Baseline (T0)
measure: 4DKL (questionnaire)
timeFrame: Baseline (T0)
measure: EQ-5D-5L (questionnaire)
timeFrame: Baseline (T0)
measure: Five Facet Mindfulness Questionnaire (questionnaire)
timeFrame: Baseline (T0)
measure: LIBRA (questionnaire)
timeFrame: Baseline (T0)
measure: Lubben Social Network Scale (questionnaire)
timeFrame: Baseline (T0)
measure: SARC-F Sarcopenia questionnaire (questionnaire)
timeFrame: Baseline (T0)
measure: Sedentary Behaviour Questionnaire (questionnaire)
timeFrame: Baseline (T0)
measure: Change in Nutritional intake (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in Perceived Stress Scale (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in Pittsburgh Sleep Quality Index (PSQI) (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in SQUASH (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Gastrointestinal symptoms questionnaire (questionnaire)
timeFrame: Baseline (T0)
measure: Gastrointestinal symptoms questionnaire (questionnaire)
timeFrame: Follow-up after 6 weeks (T1)
measure: Bristol stool chart (questionnaire)
timeFrame: Baseline (T0)
measure: Bristol stool chart (questionnaire)
timeFrame: Follow-up after 6 weeks (T1)
measure: Gut transit time
timeFrame: Baseline (T0)
measure: Gut transit time
timeFrame: Follow up after 6 weeks (T1)
measure: Change in Cognitive Failures Questionnaire (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in Cognitive Emotions Regulation Questionnaire (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in Hospital Anxiety and Depression Scale (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in Memory Self-Efficacy MIA (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: Change in Starkstein Apathy Scale (questionnaire)
timeFrame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
measure: User experiences (questionnaire)
timeFrame: Follow up after 6 weeks (T1)
measure: COVID status (questionnaire)
timeFrame: Baseline (T0)
measure: COVID status (questionnaire)
timeFrame: Follow up after 6 weeks (T1)
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University, Donders Centre for Cognitive Neuroimaging
state: Gelderland
city: Wageningen
country: Netherlands
facility: Wageningen University and Research, Division of Human Nutrition and Health
state: Gelderland
Study officials:
affiliation: Radboud University, Donders Centre for Cognitive Neuroimaging
name: Esther Aarts, prof. dr.
role: PRINCIPAL_INVESTIGATOR
References: