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Completed

NCT Number: NCT05777863

The Effects of a Multidomain Lifestyle Intervention on Brain Functioning and Its Relation With Immunometabolic Markers in Ageing

HELI is a multicenter, randomised controlled trial in two Dutch research centres (Donders Centre for Cognitive Neuroimaging, Nijmegen, and the department of Human Nutrition & Health at Wageningen University) among 104 older adults aged 60-75 years who are at risk for cognitive decline with an intervention duration of 26 weeks (roughly 6 months). Participants are randomized in a 1:1 ratio to a multidomain lifestyle intervention characterized by group-sessions and guidance (high-intensity intervention group) versus online access to general lifestyle-related health information in the form of biweekly leaflets (low-intensity intervention group).

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Key information

Conditions

Life Style Aging Behavior Cognition Disorders Cognitive Decline Cognitive Dysfunction Mental Disorders Neurocognitive Disorders Risk Reduction Risk Reduction Behavior

Age range

60 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Donders Centre for Cognitive Neuroimaging, Nijmegen, Gelderland, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Written informed consent;
  • Age between 60-75 years (at pre-screening);
  • Fluency in Dutch (speaking, reading and writing);
  • Lives near study centres in Nijmegen and Wageningen (max. 50 kilometers of travelling, to ensure study centre visits are possible without excessive travel burden);
  • Presence of ≥2 self-reported risk factors for cognitive decline (BMI of 30 or higher, physical inactivity according to World Health Organization guidelines, hypertension [not using hypertensive drugs counts as an additional risk factor], hypercholesterolemia, diabetes type-II, non-symptomatic cardiovascular disease).

Exclusion criteria

  • Concurrent participation in other intervention trials;
  • Technologically illiterate (complete incompetence in working with computers, apps, online questionnaires, etc.);
  • No internet access from home;
  • Clinical diagnosis of ≥1 of the following: vascular event (CVA), neurological pathology (e.g. mild cognitive impairment, dementia, multiple sclerosis, Parkinson's, epilepsy), current malignant disease(s) (with or without current treatment), current psychiatric disorder(s) (e.g. depression, psychosis, bipolar episodes), symptomatic cardiovascular disease (e.g. stroke, angina pectoris, heart failure, myocardial infarction), revascularisation surgery in the last 12 months at pre-screening, inflammatory bowel disease (characterised with diarrhoea), visual impairment (e.g. blindness), hearing or communicative impairment;
  • Unable to undergo MRI (e.g. metal objects in upper body, past brain surgery, active implants, claustrophobic);
  • Cognitive impairment as determined by the Telephone Interview for Cognitive Status (TICS-M1), performed during pre-screening before inclusion.

Treatment and study plan

Multidomain lifestyle intervention

Behavioral

A multidomain lifestyle intervention including the following lifestyle domains: (1) diet, (2) physical activity, (3) sleep, (4) stress/mindfulness, and (5) cognitive training.

Primary outcomes

  1. Change in brain activity during working memory

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Blood-oxygen level dependent activity during N-back (2-back) fMRI task

  2. Change in working memory performance

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Task accuracy during N-back (2-back) fMRI task

  3. Change in cerebral perfusion levels

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Cerebral perfusion measured using arterial spin labelling (ASL)

  4. Change in inflammatory profile in blood plasma: hs-CRP

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Blood plasma inflammatory profile analysis to measure hs-CRP level

  5. Change in inflammatory profile in blood plasma: IL-6

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Blood plasma inflammatory profile analysis to measure IL-6 level

  6. Change in inflammatory profile in blood plasma: TNF-α

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Blood plasma inflammatory profile analysis to measure TNF-α level

  7. Change in microbiota profile

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    16S rRNA based profile of gut microbiota in faeces

Secondary outcomes

  1. Change in Body mass index

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Measured in kg/m^2

  2. Change in Waist circumference

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Measured in cm

  3. Change in Hip circumference

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Measured in cm

  4. Change in Blood pressure

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

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

  5. Change in Abdominal fat distribution (neuroimaging)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Visceral adipose tissue(VAT)/subcutaneous adipose tissue (SAT) ratio measured by abdominal T1-weighted MRI scan

  6. Change in Brain structure volume profile (neuroimaging)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Brain structure volumes (grey matter, white matter, brain vesicles), measured by MP2RAGE structural sequence

  7. Change in Brain myo-inositol levels (neuroimaging)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Brain myo-inositol levels reflecting local neuroinflammation in dorsolateral prefrontal cortex and hippocampus, measured by magnetic resonance spectroscopy (MRS)

  8. Intracranial iron deposition (neuroimaging)

    Time frame: Baseline (T0)

    Local aggregation of iron deposition within the brain, measured by quantitative susceptibility mapping (QSM)

  9. Change in Neuropsychological test battery scoring

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

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

  10. Change in Trail Making Test A (TMT-A) Numbers : trial time (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - no maximum (seconds to assessment completion). Lower score indicates a better outcome

  11. Change in Trail Making Test A (TMT-A) Numbers: errors (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - no maximum (amount of errors). Lower score indicates a better outcome

  12. Change in Trail Making Test B (TMT-B) Numbers and Letters : trial time (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - no maximum (seconds to assessment completion). Lower score indicates a better outcome

  13. Change in Trail Making Test B (TMT-B) Numbers and Letters: errors (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - no maximum (amount of errors). Lower score indicates a better outcome

  14. Change in Verbal Fluency Test (VFT) (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Word count in one minute; score 0 - no maximum. Higher score indicates a better outcome

  15. Change in Rey Auditory Verbal Learning Test (RAVLT): learning trials (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - 15 (amount of words remembered during learning trial 1 to 5). Higher score indicates a better score

  16. Change in Rey Auditory Verbal Learning Test (RAVLT): delayed recall (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - 15 (amount of words remembered during delayed recall). Higher score indicates a better score

  17. Change in Digit Symbol Substitution Test (DSST) (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - 90 (amount of symbols correctly substituted). Higher score indicates better outcome

  18. Change in Wechsler Adult Intelligence Scale (WAIS) digit span (cognitive assessment)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Discrete number; score 0 - 90 (amount of digit spans correctly repeated). Higher score indicates better outcome

  19. Change in Five Facet Mindfulness Questionnaire (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Self-assessment of mindfulness; score 24 - 120. Higher score indicate more mindfulness

  20. Change in Sedentary Behaviour Questionnaire (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Average hours and minutes of sedentary behavior a day; score 0 - 24 hours. Higher score (more hours) indicates more sedentary behavior

  21. Change in Eetscore food questionnaire (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Dutch Healthy Diet Index 2015; score 0 - 160. Higher score indicates a better outcome

  22. Change in Perceived Stress Scale (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Stress perception; score 0 - 40. Higher score indicate more perceived stress

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

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Sleep quality; score 0 - 21. Higher score (referred to as global or total score) indicates worse sleep quality

  24. Change in SQUASH (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    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)

  25. Change in Cognitive Failures Questionnaire (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Subjective cognitive functioning; score 0 - 100. A higher score indicates more subjective cognitive failure

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

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    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 (score 23 - 115, higher score indicates better memory self-efficacy) and Part 2B: Locus (score 7 - 35, higher scores indicate better perceived personal control over remembering abilities)

  27. Change in total amount of bacteria, fungi and specific bacterial strains (faeces)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Total amount of bacteria, fungi and specific bacterial strains are quantified using digital droplet PCR in faecal samples

  28. Change in individual short-chain fatty acids (SCFAs) profile (faeces)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    GC-MS and LC-MS measurements to assess profile of individual SCFAs in faecal samples (acetic acid, formic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, 4-methyl valeric acid, hexanoic acid, heptanoic acid)

  29. Change in microbiome-derived bioactive compounds (faeces)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Amount of microbiome-derived bioactive compounds is measured by untargeted LC-MS microbiota-derived metabolite analysis in faecal samples

  30. Change in intestinal inflammation profile (faeces)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Assay-based profile of intestinal inflammation measured in faecal samples

  31. Change in Gut transit time

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

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

  32. Change in metabolic profile (blood)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

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

  33. Change in inflammation profile (blood)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Assay-based profile of systemic inflammation measured in plasma samples

  34. Change in intestinal integrity profile (blood)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Assay-based profile of intestinal integrity measured in plasma samples

  35. Change in brain health profile (blood)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Assay-based profile of brain health measured in plasma samples

  36. Change in white blood cell count (blood)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    White blood cell count measured via finger prick analysis

  37. Change in small intestinal bacterial overgrowth (SIBO) (breath)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Measurement of total exhaled hydrogen gas after glucose consumption in breath samples

Other outcomes

  1. Montreal Cognitive Assessment (MOCA) (cognitive assessment)

    Time frame: Baseline (T0)

    Discrete number; score 0 - 30. Higher score indicates better cognitive performance (≥26 indicates normal cognitive functioning)

  2. Baseline Demographics and medical history (questionnaire)

    Time frame: Baseline (T0)

    Demographic information, medical history and medication use - qualitative assessment

  3. Change in 4DKL (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    (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)

  4. Change in EQ-5D-5L (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Quality of life; score 0 - 100. Higher score indicate better quality of life

  5. Change in LIBRA (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Modifiable dementia risk using lifestyle for brain health; score -5.9 - +12.7. Higher score indicates a worse outcome (higher dementia risk)

  6. Change in Lubben Social Network Scale (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Social contact and perceived social support; score 0 - 30. Higher score indicates a better outcome (higher level of perceived social support)

  7. Change in SARC-F Sarcopenia questionnaire (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

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

  8. Change in Cognitive Emotions Regulation Questionnaire (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    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

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

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Anxiety and depression; separate scores for anxiety (0 - 21) and depression (0 - 21). For each domain, a score >8 indicates psychiatric condition of anxiety or depression

  10. Change in Starkstein Apathy Scale (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    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

  11. Change in COVID status (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Vaccination status, COVID history - qualitative assessment

  12. Change in Gastrointestinal symptoms questionnaire (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Gastrointestinal symptoms, qualitative assessment

  13. Change in Bristol stool chart (questionnaire)

    Time frame: Change between Baseline (T0) and Follow-up after 6 months (T1)

    Classification of faeces type, qualitative assessment

Sponsors and collaborators

Lead sponsor

Donders Centre for Cognitive Neuroimaging

Other

Collaborators

  • Wageningen University and Research

Registry information

Official study title

The Effects of a Multidomain Lifestyle Intervention on Brain Functioning and Its Relation With Immunometabolic Markers in Ageing: the HELI Study

Acronym: HELI

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Mar 21, 2023
Registry last updated
Jun 21, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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