The Effects of a Colon-delivered Multivitamin Supplement on Brain Functioning and Its Relation With Immunometabolic and Intestinal Markers in Ageing: the COMBI Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 4
- 主要终点
- Change in brain activity during working memory
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Stratified 1 to 1 randomization will be automatically performed in Castor. Participant, Investigator and Outcome Assessor will not be aware of the treatment group. An independent researcher will have access to randomization details, and make sure the participant will receive the correct supplement type.
入排标准
- 年龄范围
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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:
- •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):
- •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.
结局指标
主要结局
Change in brain activity during working memory
时间窗: 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 faecal short-chain fatty acids
时间窗: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Total faecal short-chain fatty acid concentration measured by gas chromatograph mass spectrometry
Change in working memory performance
时间窗: Change between Baseline (T0), Follow-up after 6 weeks (T1)
Task accuracy during N-back fMRI task
次要结局
- Change in neuropsychological test-battery scoring(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in stool redox potential (faecal)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in brain myo-inositol levels (neuroimaging)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in cerebral perfusion levels (neuroimaging)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in microbiota profile (faecal)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in individual short-chain fatty acids profile (faecal)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in stool water content (faecal)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in stool pH (faecal)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in intestinal inflammation profile (faecal)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in C-reactive protein concentration (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in white blood cell count (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in inflammation profile (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in brain health profile (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in intestinal integrity profile (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in anti-oxidant status profile (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in metabolic profile (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))
- Change in vitamin profile (blood)(Change between Baseline (T0), Follow-up after 6 weeks (T1))