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CompletedNCT05675007COMBIUpdated Jun 21, 2024

Effects of a Colon-delivered Multivitamin Supplement on Brain Functioning, Immunometabolic- and Intestinal Markers in Ageing

An interventional study of Colon-delivered multivitamin supplement and Placebo capsule in Cognitive Decline and Aging, sponsored by Donders Centre for Cognitive Neuroimaging. Completed at 2 sites in Netherlands. Open to participants aged 60 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-06-21.

Sponsored by Donders Centre for Cognitive Neuroimaging · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
75
Allocation
Randomized
Ages
60 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cognitive Decline
  • Aging

Keywords

  • Intestinal health
  • Gut-brain axis
03

In context

Cognitive Dysfunction

3,842 studies on the registry are indexed under Cognitive Dysfunction; 1,099 are open to participants now.

This study's enrollment of 75 is above the median of 65 across 2,807 interventional studies indexed under Cognitive Dysfunction.

Browse Cognitive Dysfunction studies →

Lead sponsor

Donders Centre for Cognitive Neuroimaging is the lead sponsor of 7 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
60 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
75 participants (actual)

Study arms

  • Experimental
    Colon-delivered multivitamin supplement

    Within this arm, study subjects will consume a colon-delivered multivitamin supplement for 6 weeks. Subjects are instructed to consume the capsule daily during breakfast. The capsule must be taken orally with a glass of water.

    Dietary Supplement: Colon-delivered multivitamin supplement

  • Placebo comparator
    Placebo

    Within this arm, study subjects will consume a placebo capsule for 6 weeks. Subjects are instructed to consume the capsule daily during breakfast. The capsule must be taken orally with a glass of water.

    Dietary Supplement: Placebo capsule

Interventions

  • Dietary supplementColon-delivered multivitamin supplement

    Colon-delivered multivitamin supplement containing the following dose of the indicated vitamin: vitamin B2 (10 mg), vitamin B3 (4.0 mg), vitamin B6 (1.4 mg), vitamin B9 (400 μg), vitamin C (200 mg) and vitamin D3 (15ug). Vitamin capsules are filled with microcrystalline cellulose and magnesium stearate up to 200 mg. Control of release in the colon is achieved by the Eudragit S 100 coating layer technology that surrounds the vitamins contained in the core capsules.

  • Dietary supplementPlacebo capsule

    Placebo capsule containing microcrystalline cellulose and magnesium stearate up to 200 mg. Placebo capsules are coated with the Eudragit S 100 coating layer.

06

What researchers measure

Primary outcomes

  1. Change in brain activity during working memory

    Blood-oxygen level dependent activity in dlPFC and hippocampus during N-back fMRI task

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  2. Change in working memory performance

    Task accuracy during N-back fMRI task

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  3. Change in faecal short-chain fatty acids

    Total faecal short-chain fatty acid concentration measured by gas chromatograph mass spectrometry

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

Secondary outcomes

  1. Change in brain myo-inositol levels (neuroimaging)

    Brain myo-inositol levels reflecting neuroinflammation in dlPFC and hippocampus, measured by magnetic resonance spectroscopy

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  2. Change in cerebral perfusion levels (neuroimaging)

    Cerebral perfusion levels measured by arterial spin labelling

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  3. Change in neuropsychological test-battery scoring

    Z-scoring on cognitive domains predominantly affected by cognitive ageing: executive function (incl. working memory), episodic memory and processing speed.

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  4. Change in microbiota profile (faecal)

    16S rRNA based profile of gut microbiota in faeces

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  5. Change in individual short-chain fatty acids profile (faecal)

    GCMS measurement to assess profile of individual SCFAs in faeces (acetic acid, formic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, 4-methyl valeric acid, hexanoic acid, heptanoic acid)

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  6. Change in stool water content (faecal)

    Water content of stool, based on wet- and dry weight.

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  7. Change in stool pH (faecal)

    Faecal pH will be measured with a pH/redox meter in faeces

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  8. Change in stool redox potential (faecal)

    Redox potential will be measured with a pH/redox meter in faeces

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  9. Change in intestinal inflammation profile (faecal)

    Assay-based profile of intestinal inflammation measured in faeces

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  10. Change in C-reactive protein concentration (blood)

    hsCRP measured via finger prick analysis

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  11. Change in white blood cell count (blood)

    White blood cell count measured via finger prick analysis

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  12. Change in inflammation profile (blood)

    Assay-based profile of systemic inflammation measured in plasma

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  13. Change in intestinal integrity profile (blood)

    Assay-based profile of intestinal integrity measured in plasma

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  14. Change in anti-oxidant status profile (blood)

    Assay-based profile of anti-oxidant status and oxidative stress measured in plasma

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  15. Change in metabolic profile (blood)

    Assay-based profile of (energy) metabolism measured in plasma

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  16. Change in brain health profile (blood)

    Assay-based profile of brain health measured in plasma

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  17. Change in vitamin profile (blood)

    Assay-based profile of circulating vitamins from supplement measured in plasma

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

Other outcomes

  1. Body mass index

    Measured in kg/m\^2

    Time frame: Baseline (T0)

  2. Waist circumference

    Measured in cm

    Time frame: Baseline (T0)

  3. Hip circumference

    Measured in cm

    Time frame: Baseline (T0)

  4. Blood pressure

    Scores range from approximately (for diastolic) 60-120 and (for systolic) 100-180 mmHg, with higher scores indicating higher blood pressure.

    Time frame: Baseline (T0)

  5. Abdominal fat distribution

    VAT(visceral adipose tissue)/SAT(subcutaneous adipose tissue) ratio based on abdominal MRI scan

    Time frame: Baseline (T0)

  6. Baseline Demographics and medical history (questionnaire)

    Demographic information, medical history and medication use - qualitative assessment

    Time frame: Baseline (T0)

  7. 4DKL (questionnaire)

    (Psychosocial) complaints in daily life. Separate scores for distress (\>10 moderate, \>20 severe), depression (\>2 moderate, \>5 severe), anxiety (\>3 moderate, \>9 severe) and somatisation (\>10 moderate, \>20 severe)

    Time frame: Baseline (T0)

  8. EQ-5D-5L (questionnaire)

    Quality of life. Scores range from 0-100, higher scores indicate better quality of life

    Time frame: Baseline (T0)

  9. Five Facet Mindfulness Questionnaire (questionnaire)

    Self-assessment of mindfulness. Total scale ranges from 24 - 120, higher scores indicate more mindfulness

    Time frame: Baseline (T0)

  10. LIBRA (questionnaire)

    Modifiable dementia risk using lifestyle for brain health. The score ranges from -5.9 (minimum score) to +12.7 (maximum score), with higher scores meaning a worse outcome (higher dementia risk)

    Time frame: Baseline (T0)

  11. Lubben Social Network Scale (questionnaire)

    Social contact and perceived social support. The score ranges from 0 (minimum score) to 30 (maximum score), with higher scores meaning a better outcome (higher level of perceived social support)

    Time frame: Baseline (T0)

  12. SARC-F Sarcopenia questionnaire (questionnaire)

    Sarcopenia. Scores range from 0 to 10 (i.e. 0-2 points for each component; 0 = best to 10 = worst).

    Time frame: Baseline (T0)

  13. Sedentary Behaviour Questionnaire (questionnaire)

    Average hours and minutes of sedentary behavior a day, range from 0 to 24 hours. Higher scores (more hours) means a more sedentary behavior.

    Time frame: Baseline (T0)

  14. Change in Nutritional intake (questionnaire)

    Nutritional intake measured with a Food Frequency Questionnaire, assessing food intake of the past month, qualitative assessment

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  15. Change in Perceived Stress Scale (questionnaire)

    Stress perception. Total score, scale 0 - 40, higher scores indicate more perceived stress

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  16. Change in Pittsburgh Sleep Quality Index (PSQI) (questionnaire)

    Sleep quality. Total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  17. Change in SQUASH (questionnaire)

    Physical activity. METs derived from the Ainsworth's compendium of physical activity will be used to classify physical activity intensity (\<1.5METs- sedentary, 1.6-2.9 METs- light, 3.0-5.9METs- moderate, \>6.0- vigorous physical activity).

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  18. Gastrointestinal symptoms questionnaire (questionnaire)

    Gastrointestinal symptoms, qualitative assessment

    Time frame: Baseline (T0)

  19. Gastrointestinal symptoms questionnaire (questionnaire)

    Gastrointestinal symptoms, qualitative assessment

    Time frame: Follow-up after 6 weeks (T1)

  20. Bristol stool chart (questionnaire)

    Classification of faeces type, qualitative assessment

    Time frame: Baseline (T0)

  21. Bristol stool chart (questionnaire)

    Classification of faeces type, qualitative assessment

    Time frame: Follow-up after 6 weeks (T1)

  22. Gut transit time

    Gut transit time measured by blue muffin consumption and appearance in faeces

    Time frame: Baseline (T0)

  23. Gut transit time

    Gut transit time measured by blue muffin consumption and appearance in faeces

    Time frame: Follow up after 6 weeks (T1)

  24. Change in Cognitive Failures Questionnaire (questionnaire)

    Subjective cognitive functioning. Score ranges from 0-100. A higher total score indicates more subjective cognitive failure.

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  25. Change in Cognitive Emotions Regulation Questionnaire (questionnaire)

    Cognitive coping strategies. Answers are scored on a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree). The scoring takes the average of all the scores in each subscale of cognitive reappraisal and expressive suppression

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  26. Change in Hospital Anxiety and Depression Scale (questionnaire)

    Anxiety and depression. Separate scores for anxiety (max 21) and depression (max 21). For each domain, a score \>8 indicates psychiatric condition of anxiety or depression.

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  27. Change in Memory Self-Efficacy MIA (questionnaire)

    Self-evaluation and confidence of memory. Sum of Part 1 + Part 2A and B. Part 1: Strategy (scores 10 - 50, higher scores indicate more use of strategies), Part 2A: Subjective memory functioning, scores ranges from 23 - 115, with higher scores indicate better memory self-efficacy and 2B: Locus, scores ranges from 7 - 35, higher scores indicate better perceived personal control over remembering abilities.

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  28. Change in Starkstein Apathy Scale (questionnaire)

    Screen and measure apathetic symptoms. A higher total score (range 0-42) indicates more severe apathy, with a score greater than 14 or greater is indicative of clinical apathy

    Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)

  29. User experiences (questionnaire)

    User experiences of the supplement - qualitative assessment.

    Time frame: Follow up after 6 weeks (T1)

  30. COVID status (questionnaire)

    Vaccination status, COVID history - qualitative assessment.

    Time frame: Baseline (T0)

  31. COVID status (questionnaire)

    Vaccination status, COVID history - qualitative assessment.

    Time frame: Follow up after 6 weeks (T1)

07

Study locations

2 sites
  • Radboud University, Donders Centre for Cognitive Neuroimaging
    Nijmegen, Gelderland 6525 EN, Netherlands
  • Wageningen University and Research, Division of Human Nutrition and Health
    Wageningen, Gelderland 6708 WE, Netherlands
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 21, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT05675007
Lead sponsor
Donders Centre for Cognitive Neuroimaging
Collaborators
Wageningen University and Research
Responsible party
Sponsor
First posted
Jan 9, 2023
Start date
Dec 5, 2022
Primary completion
May 2, 2024
Completion
May 2, 2024
Last update
Jun 21, 2024

Study contacts

Esther Aarts, prof. dr.
principal investigator · Radboud University, Donders Centre for Cognitive Neuroimaging

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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