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

NCT ID: NCT05675007

Last Updated: 2024-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-05
• Study Completion Date: 2024-05-02

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.

Conditions

Cognitive Decline; Aging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Colon-delivered multivitamin supplement

Intervention Type: DIETARY_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

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.

Group Type: PLACEBO_COMPARATOR

Placebo capsule

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Colon-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.

Intervention Type: DIETARY_SUPPLEMENT

Placebo capsule

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

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Wageningen University and Research

OTHER

Sponsor Role: collaborator

Donders Centre for Cognitive Neuroimaging

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esther Aarts, prof. dr.

Role: PRINCIPAL_INVESTIGATOR

Radboud University, Donders Centre for Cognitive Neuroimaging

Locations

Radboud University, Donders Centre for Cognitive Neuroimaging

Nijmegen, Gelderland, Netherlands

Wageningen University and Research, Division of Human Nutrition and Health

Wageningen, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

3033003.02

Identifier Type: -

Identifier Source: org_study_id