Cognitive DeclineCOMBINCT05675007
Effects of a Colon-delivered Multivitamin Supplement on Brain Functioning, Immunometabolic- and Intestinal Markers in Ageing
A study testing Colon-delivered multivitamin supplement in people with Cognitive Decline and Aging, run by Donders Centre for Cognitive Neuroimaging at 2 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 60 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Decline, Aging
- What is being tested?
- Colon-delivered multivitamin supplement
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 2 sitesNetherlands
- Study dates
- 5 Dec 2022to 2 May 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Show all 11Show fewer
- Hypertension (1 point)
- Hypertension without medication (1 point)
- Hypercholesterolemia (1 point)
- Diabetes type II (1 point)
- Mild cardiovascular disease (1 point)
Who cannot join
- 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;
Show all 25Show fewer
- 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):
- Are there metal objects located in your upper body? Exception: tooth-fillings and/or dental crowns.
- Are there metal splinters in your body, in particular within the eyes? For example: through labour work in the metal industry.
- Are there jewellery items or piercings that you are unable to take off?
- Have you had a brain surgery in the past?
- Are there active implants present? For example: pacemaker, neurostimulator, insulin pump, hearing aid (that is unable to be removed).
- Are there any medical plasters or patches that you can't or may not take off? For example: nicotine patch.
- Do you suffer from epilepsy?
- 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.
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Radboud University, Donders Centre for Cognitive Neuroimaging
Nijmegen, Gelderland, 6525 EN
Wageningen University and Research, Division of Human Nutrition and Health
Wageningen, Gelderland, 6708 WE
About this study
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
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.
- Conditions
- Cognitive Decline, Aging
- Being tested
- Colon-delivered multivitamin supplement, Placebo capsule
- Keywords
- Intestinal health, Gut-brain axis
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colon-delivered multivitamin supplementDietary 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.
Placebo capsuleDietary supplement
Placebo capsule containing microcrystalline cellulose and magnesium stearate up to 200 mg. Placebo capsules are coated with the Eudragit S 100 coating layer.
| Study group | Role | What they receive |
|---|---|---|
| Colon-delivered multivitamin supplement | Experimental | 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. Receives: Dietary Supplement: Colon-delivered multivitamin supplement |
| Placebo | Placebo comparator | 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. Receives: Dietary Supplement: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in brain activity during working memory
Blood-oxygen level dependent activity in dlPFC and hippocampus during N-back fMRI task
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in working memory performance
Task accuracy during N-back fMRI task
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in faecal short-chain fatty acids
Total faecal short-chain fatty acid concentration measured by gas chromatograph mass spectrometry
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Secondary outcomes (17)
Change in brain myo-inositol levels (neuroimaging)
Brain myo-inositol levels reflecting neuroinflammation in dlPFC and hippocampus, measured by magnetic resonance spectroscopy
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in cerebral perfusion levels (neuroimaging)
Cerebral perfusion levels measured by arterial spin labelling
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
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.
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in microbiota profile (faecal)
16S rRNA based profile of gut microbiota in faeces
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
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)
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in stool water content (faecal)
Water content of stool, based on wet- and dry weight.
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in stool pH (faecal)
Faecal pH will be measured with a pH/redox meter in faeces
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in stool redox potential (faecal)
Redox potential will be measured with a pH/redox meter in faeces
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in intestinal inflammation profile (faecal)
Assay-based profile of intestinal inflammation measured in faeces
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in C-reactive protein concentration (blood)
hsCRP measured via finger prick analysis
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in white blood cell count (blood)
White blood cell count measured via finger prick analysis
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in inflammation profile (blood)
Assay-based profile of systemic inflammation measured in plasma
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in intestinal integrity profile (blood)
Assay-based profile of intestinal integrity measured in plasma
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in anti-oxidant status profile (blood)
Assay-based profile of anti-oxidant status and oxidative stress measured in plasma
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in metabolic profile (blood)
Assay-based profile of (energy) metabolism measured in plasma
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in brain health profile (blood)
Assay-based profile of brain health measured in plasma
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in vitamin profile (blood)
Assay-based profile of circulating vitamins from supplement measured in plasma
Measured: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2023
- Study start5 Dec 2022
- Primary completion2 May 2024
- Study completion2 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive DeclineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Donders Centre for Cognitive Neuroimaging
- Sponsor type
- University, hospital or other
- Collaborators
- Wageningen University and Research
- Responsible party
- Sponsor
- Investigators
- Esther Aarts, prof. dr., Principal investigator, Radboud University, Donders Centre for Cognitive Neuroimaging
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05675007
- Sponsor's protocol ID
- 3033003.02
- Acronym
- COMBI
- Status last verified
- May 2024
- First submitted
- 24 Oct 2022
- Last updated
- 21 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05675007
- Acronym / sponsor ID
- COMBI / 3033003.02
- Conditions
- Cognitive Decline, Aging
- Keywords
- Intestinal health, Gut-brain axis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Donders Centre for Cognitive NeuroimagingUniversity, hospital or other
- Collaborators
- Wageningen University and Research
- Study start
- 5 Dec 2022 (actual)
- Primary completion
- 2 May 2024 (actual)
- Study completion
- 2 May 2024 (actual)
- First posted
- 9 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Colon-delivered multivitamin supplement | Experimental | Dietary Supplement: Colon-delivered multivitamin supplementWithin 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. |
| Placebo | Placebo comparator | Dietary Supplement: Placebo capsuleWithin 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. |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
Key exclusion criteria (25 listed)
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Colon-delivered multivitamin supplementColon-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 supplement | Colon-delivered multivitamin supplement |
| Placebo capsulePlacebo capsule containing microcrystalline cellulose and magnesium stearate up to 200 mg. Placebo capsules are coated with the Eudragit S 100 coating layer. | Dietary supplement | Placebo |
Primary outcome
Change in brain activity during working memory
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Blood-oxygen level dependent activity in dlPFC and hippocampus during N-back fMRI task
Change in working memory performance
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Task accuracy during N-back fMRI task
Change in faecal short-chain fatty acids
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Total faecal short-chain fatty acid concentration measured by gas chromatograph mass spectrometry
17 secondary outcomes
Change in brain myo-inositol levels (neuroimaging)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in cerebral perfusion levels (neuroimaging)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in neuropsychological test-battery scoring
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in microbiota profile (faecal)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in individual short-chain fatty acids profile (faecal)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in stool water content (faecal)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in stool pH (faecal)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in stool redox potential (faecal)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in intestinal inflammation profile (faecal)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in C-reactive protein concentration (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in white blood cell count (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in inflammation profile (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in intestinal integrity profile (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in anti-oxidant status profile (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in metabolic profile (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in brain health profile (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Change in vitamin profile (blood)
Time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2024.
Related trials for Cognitive Decline
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Recruiting
HEARS-NPS: Addressing Hearing Loss as a Common Unmet Contributor of Neuropsychiatric Symptoms
Alzheimer Disease, Dementia
RecruitingObservational study
Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Esther Aarts, prof. dr. principal investigator
Radboud University, Donders Centre for Cognitive Neuroimaging
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Colon-delivered multivitamin supplement in people with Cognitive Decline and Aging, run by Donders Centre for Cognitive Neuroimaging at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in brain activity during working memory (time frame: Change between Baseline (T0), Follow-up after 6 weeks (T1)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2024.